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APPROVED FOR RESTRICTED USE IN EMERGENCY SITUATION OF COVID-19 ANNEXURE C to MODULE I SUMMARY OF PRODUCT CHARACTERISTICS Doc. No. SPC/71108 Ver.3 1. NAME OF THE MEDICINAL PRODUCT. • Novel Corona Virus 2019-nCoV Vaccine (Recombinant) 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each 0.1ml contains: DNA plasmid construct with spike protein gene region from SARS- 1.0 mg CoV-2 virus produced in E.coli Phosphate Buffered saline q.s. 3. PHARMACEUTICAL FORM Solution for Intradermal Injection. Each dose consists of three shots of 0.1 mL each CAUTION – Dose and Regimen Selection 3mg – 2 Dose Regimen: 3 shots of 0.1 ml each should be given on day 0 and 28 3x 0.1ml 3x 0. 1ml Day 28 Day 0 It is recommended to use the vaccine only with Pharmajet Device. Using it with conventional needle and syringe will not lead to optimal immunogenicity response and will affect the efficacy of the vaccine. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications ZYCOV-D® is indicated for active immunisation to prevent COVID-19 caused by SARSCoV-2 in individuals 12 years of age and older when given in two separate doses of 3mg (0.3ml) each to be given at an interval of 28 days each (day 0, day 28). ZYCOV-D® is approved for restricted use in emergency situation of COVID-19. Page 1 of 134.2 Posology and method of administration This vaccination schedule consists of 2 separate doses to be given at an interval of 28 days each (day 0 and day 28). Each dose consists of three shots of 0.1ml each given by needle free injector (Pharmajet Tropis device) via intradermal route at three separate sites (2 shots on one arm (recommended distance between two shots is at least 5 cms) and 1 shot on other arm). Method of Administration: ZYCOV-D® has to be given by intradermal route only using needle free injector (Pharmajet Tropis device). Kindly refer Medication Guide for step by step guidance on Method of Administration. 4.3 Contraindications ZYCOV-D® is contraindicated in individuals known to have hypersensitivity to the active substance or to any of the excipients. 4.4 Special warnings and precautions for use Hypersensitivity As with all injectable vaccines, appropriate medical treatment and supervision should always be readily available in case of an anaphylactic event following the administration of the vaccine. Concurrent Illness As with other vaccines, administration of ZYCOV-D® should be postponed in individuals suffering from an acute severe febrile illness. However, the presence of a minor infection, such as cold, and/or low-grade fever should not delay vaccination. Immunocompromised individuals It is not known whether individuals with impaired immune responsiveness, including individuals receiving immunosuppressant therapy, will elicit the same response as immunocompetent individuals to the vaccine regimen. Immunocompromised individuals may have relatively weaker immune response to the vaccine regimen. Page 2 of 13Duration and level of protection The duration of protection has not yet been established. As with any vaccine, vaccination with ZYCOV-D® may not protect all vaccine recipients. Interchangeability No data are available on the use of ZYCOV-D® in persons that have previously received partial / complete vaccine series with another COVID-19 vaccine. 4.5 Interaction with other medicinal products and other forms of interaction No interaction studies have been performed. Concomitant administration of ZYCOV-D® with other vaccines has not been studied. 4.6 Special Population Elderly Population: Efficacy and safety data are currently limited in individuals ≥ 60 years of age. No dosage adjustment is required in elderly individuals ≥ 60 years of age. Paediatric Population: Efficacy and safety data are currently limited in adolescents aged 12 to <18 years. The safety and efficacy of ZYCOV-D® in children (aged <12 years old) has not yet been established. Fertility There is no clinical data on the effect of ZYCOV-D® on fertility. Pregnancy The safety and efficacy of ZYCOV-D® in pregnancy has not been established. Breastfeeding The safety and efficacy of ZYCOV-D® in lactating females has not been established. 4.7 Effects on ability to drive and use machines ZYCOV-D® has no or negligible influence on the ability to drive and use machines. However, some of the adverse reactions may temporarily affect the ability to drive or use machines. Page 3 of 134.8 Undesirable effects Phase I/II Study: A total of 1048 subjects were enrolled in the Phase I/II study, comprising of 4 different arms as follows: • Arm 1: 1mg dose given by needle and syringe • Arm 2: 1mg dose given by Pharmajet • Arm 3: 2mg dose given by needle and syringe • Arm 4: 2mg dose given by Pharmajet The age group and demographic characteristics of the subjects enrolled in Phase I/II study are as follows Phase I: 48 adult subjects Arm 1, 1 mg Arm 2, 1 mg Arm 3, 2 mg Arm 4, 2 mg (0.1 mL needle (0.1 mL (0.2 mL needle (0.2 mL and syringe) Pharmajet) and syringe) Pharmajet) Adult subjects 12 12 12 12 (Male) Mean Age 35.4 31.8 35.1 37.2 (Years) Phase II: 1000 subjects Arm 1, 1 mg Arm 2, 1 mg Arm 3, 2 mg Arm 4, 2 mg (0.1 mL needle (0.1 mL (0.2 mL needle (0.2 mL and syringe) Pharmajet) and syringe) Pharmajet) N 251 249 250 250 Male 188 186 179 177 Female 63 63 71 73 Adolescent 04 06 06 02 Mean Age 35.0 ± 11.83 34.2 ± 12.11 35.4 ± 10.46 34.6 ± 10.43 (Years) Adverse events reported in Phase I Study with 2mg Pharmajet Arm: Solicited adverse events: Tenderness at the site of injection. Unsolicited adverse events: Low WBC count. Page 4 of 13Adverse events reported in Phase II Study with 2mg Pharmajet Arm: Solicited adverse events: Nausea, fatigue, injection site erythema, injection site pain, injection site pruritus, injection site swelling, pyrexia, myalgia and headache. Frequency and Percentages of Participants with Solicited Local and systemic adverse events and unsolicited adverse events after each dose – Safety population ZyCoV-D n(%) Placebo n(%) Dose I Dose II Dose III Dose I Dose II Dose III (N = 200) (N = 197) (N = 194) (N = 50) (N = 49) (N = 48) AE Terms n(%) n(%) n(%) n(%) n(%) n(%) Solicited Local AEs Pain at injection site 7 (3.50) 9 (4.57) 6 (3.09) 0 (0.00) 0 (0.00) 0 (0.00) Redness at injection 9 (4.50) 10 (5.08) 9 (4.64) 0 (0.00) 0 (0.00) 0 (0.00) site Swelling at injection 5 (2.50) 6 (3.05) 5 (2.58) 0 (0.00) 0 (0.00) 0 (0.00) site Itching at injection 1 (0.50) 7 (3.55) 2 (1.03) 0 (0.00) 0 (0.00) 0 (0.00) site Muscle pain 1 (0.50) 0 (0.00) 1 (0.52) 0 (0.00) 0 (0.00) 0 (0.00) Solicited Systemic AEs Fatigue 3 (1.50) 1 (0.51) 0 (0.00) 0 (0.00) 0 (0.00) 1 (2.08) Fever 2 (1.00) 1 (0.51) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Headache 3 (1.50) 1 (0.51) 0 (0.00) 1 (2.00) 0 (0.00) 1 (2.08) Nausea 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) 1 (2.08) Un Solicited Systemic AEs Covid-19 2 (1.00) 0 (0.00) 2 (1.03) 0 (0.00) 0 (0.00) 1 (2.08) Nasal Dryness 1 (0.50) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) High Blood Pressure 1 (0.50) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Arthralgia 0 (0.00) 1 (0.51) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Body ache 0 (0.00) 3 (1.52) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Chikungunya virus 0 (0.00) 1 (0.51) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) infection Cough 0 (0.00) 2 (1.02) 1 (0.52) 0 (0.00) 0 (0.00) 0 (0.00) Pyrexia 0 (0.00) 5 (2.54) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Headache 0 (0.00) 2 (1.02) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Myalgia 0 (0.00) 1 (0.51) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Rhinorrhoea 0 (0.00) 1 (0.51) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Asthenia 0 (0.00) 1 (0.51) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Dysuria 0 (0.00) 0 (0.00) 1 (0.52) 0 (0.00) 0 (0.00) 0 (0.00) Fatigue 0 (0.00) 0 (0.00) 1 (0.52) 0 (0.00) 0 (0.00) 0 (0.00) N = number of subjects in the specified treatment arm; n = Number of participants with the specified event Page 5 of 13Serious adverse events: 4 subjects experienced 7 serious adverse events: viral pneumonia, in- patient hospitalization [due to discharge at elbow site, pyrexia, arthralgia, joint swelling, erythema], surgical removal of orthopaedic implant, acute coronary syndrome, left ventricular failure with bronchopneumonia, and COVID-19 (02). None of these serious adverse events was related to IP. All the adverse events reported in Phase I/II studies resolved without sequelae. Adverse Events reported from Phase III Study - 2mg-3dose regimen (Interim data): In our ongoing Phase III clinical trial, a total of 27703 subjects have been enrolled till the interim analysis. Amongst them more than 900 subjects belonged to the adolescent age group (12-17 years). The age group and demographic characteristics of the subjects enrolled in Phase III study are as follows: Phase III: 27703 subjects (Data at the time of interim analysis), Total sample size: 28216 Vaccine, 2 mg Placebo Total (0.2 mL Pharmajet) Age (in Years) Mean 36.4 36.6 36.5 Age (12-17) 448 487 935 Age ( 18-60) 12364 12338 24702 Age (above 60) 1039 1027 2066 Gender Female 4506 4605 9111 Male 9345 9247 18592 Subjects at risk(Co-morbidities) 709 740 1449 Stable Chronic Heart Disease 167 155 322 Stable Chronic Lung Disease 13 7 20 Controlled Diabetic 275 289 564 Stable Liver Disease 2 3 5 Severe Obesity 18 14 32 Other Stable Co-morbid 295 293 588 The safety profile of the adolescent age group and the overall population has been found to be same. The common solicited and unsolicited adverse events reported in total population are as under: Page 6 of 13Solicited Local Adverse Events: The most frequently reported solicited local adverse events across all treated subjects in both groups (ZYCOV-D® and Placebo) were pain at injection site: (0.66% and 0.62% after Dose 1; 0.34% and 0.35% after Dose 2 and 0.27% and 0.26% after Dose 3), redness: (0.31% and 0.28% after Dose 1; 0.19% and 0.09% after Dose 2 and 0.17% and 0.09% after Dose 3), swelling: (0.27% and 0.28% after Dose 1; 0.08% and 0.06% after Dose 2 and 0.09% and 0.05% after Dose 3) and itching: 0.08% and 0.14% after Dose 1; 0.05% and 0.07% after Dose 2 and 0.02% and 0.05% after Dose 3). Most of the adverse events were mild or moderate in severity. These events were comparable between ZYCOV-D® and placebo groups. Solicited Systemic Adverse Events: The most commonly reported solicited systemic adverse events across all treated subjects in both groups (ZYCOV-D® and Placebo) were headache (0.25% and 0.22% after Dose 1; 0.20% and 0.24% after Dose 2 and 0.16% and 0.17% after Dose 3), fever (0.20% and 0.14% after Dose 1; 0.14% and 0.21% after Dose 2 and 0.13% and 0.10% after Dose 3), muscle pain (0.19% and 0.28% after Dose 1; 0.11% and 0.18% after Dose 2 and 0.11% and 0.09% after Dose 3), and fatigue (0.19% and 0.19% after Dose 1; 0.14% and 0.16% after Dose 2 and 0.09% and 0.13% after Dose 3). Most of the adverse events were mild or moderate in severity. These events were comparable between ZYCOV-D® and placebo groups. Unsolicited Adverse Events: Arthralgia, Back pain, Muscle spasms, Myalgia, Musculoskeletal pain, Neck pain, Vertigo, Diarrhoea, Gastritis, Gastrooesophageal reflux disease, Nausea, Vomiting, Asthenia, Chills, Eye irritation, Abdominal distension, Abdominal pain, Fatigue, Pain, Pyrexia, Nasopharyngitis, Pain in extremity, Ageusia, Anosmia, Cerebral infarction, Dizziness, Headache, Cough, Dyspnoea, Nasal dryness, Oropharyngeal pain, Rhinorrhoea, Sneezing. Serious adverse events: As per interim analysis report, 15 serious adverse events were identified: stroke (02), Death due to Cardiorespiratory arrest with septicaemia and alcoholic liver disease (1), Death due to COVID19 (1), Gram negative enteritis (1) and COVID19 (10). None of these serious adverse events was related to IP. Page 7 of 13Adverse Events reported from Phase I/II Study - 3mg-2dose regimen: A total of 150 adults healthy subjects >18 years of age were enrolled in the Phase I/II study of 3mg – 2 dose regimen (100 in Vaccine arm and 50 in the Placebo arm). The age group and demographic characteristics of the subjects enrolled in Phase I/II study are as follows: Vaccine (N = 100) Placebo (N = 50) Mean Age (years) 34.2 36.7 Male 68 (68.0%) 30 (60.0%) Female 32 (32.0%) 20 (40.0%) The following adverse events were reported during the study: Local site adverse events: Pain (1.9%), Redness (1.4%), Swelling (1.2%), Itching (0.5%) Systemic adverse events: Headache (2.6%), Tiredness / Fatigue (2.1%), Fever (1.1%), Diarrhea (0.5%) and Nausea (0.5%). Adverse Events reported from Phase III Study - 3mg-2dose regimen: In our ongoing Phase III clinical trial of 3mg – 2 dose regimens, a total of 3000 healthy subjects >12 years of age have been enrolled. Amongst them 1193 subjects belonged to the adolescent age group (12-17 years). The age group and demographic characteristics of the subjects enrolled in Phase III study are as follows: Total Total Total (N = 3000) (N = 1807) (N = 1193) Mean Age (Years) 27.4 35.9 14.6 Male 1907 (63.6%) 1278 (70.7%) 629 (52.7%) Female 1093 (36.4%) 529 (29.3%) 564 (47.3%) The safety profile of the adolescent age group and the adult population has been found to be similar. The adverse events reported in total population up to day 112 are as under: Local site adverse events: Pain (1.9%), Redness (0.7%), Swelling (0.4%), Itching (0.3%) Solicited systemic adverse events: Headache (0.4%), Tiredness / Fatigue (0.2%), Fever (0.4%), arthralgia (0.2%), myalgia (0.1%) and vomiting (0.01%). Unsolicited systemic adverse events: Body ache (0.13%), Weakness (0.12%), Headache (0.08%), Cough and Cold (0.08%), Fever (0.07%), Diarrhoea (0.05%), Tiredness (0.03%), COVID-19 (0.06%), Myalgia (0.01%) and Vomiting (0.01%). Page 8 of 134.9 Overdose Experience of overdose is limited. There is no specific treatment for an overdose with ZYCOV-D® In the event of an overdose, the individual should be monitored and provided with symptomatic treatment as appropriate. 5. PHARMACOLOGICAL PROPERTIES 5.1 Mechanism of Action The plasmid construct of ZYCOV-D® carrying the spike-S gene of interest enters host cells, where it remains in the nucleus as an episome; without getting integrated into the host cell DNA. Thus, using the host cell’s protein translation machinery, the inserted cloned gene in the episome will direct the synthesis of the antigen it encodes. The protein produced by plasmid- transfected cells is likely to be expressed within the cell and folded in its native conformation. Further the signal peptide prompts cells to translocate the protein, usually to the cellular membrane. The antigen is recognized by antigen presenting cells (APCs) and further induces antibodies including neutralizing antibodies and cellular immune response through major histocompatibility complex (MHC). 5.2 Pharmacodynamics properties Immunogenicity Data 28 days after last dose from Phase II and Phase III Clinical Trials (2mg- 3dose regimen with Pharmajet): Phase II Clinical Trial: Parameter Data Seroconversion rate based on IgG* (%) 91.28% Seroconversion rate based on Neutralizing Antibody 88.89% response^ (%) GMT based on Neutralizing Antibody response^ 131.32 (63.50, 271.58)$ GMFR based on Neutralizing Antibody response^ 22.56 (10.57, 48.16) $ *by S1 antigen ELISA ^Wild type virus neutralization assay (PRNT ) 50 $ data presented as Geometric Mean (95% CI) Page 9 of 13Phase III Clinical Trial: Parameter Data Seroconversion rate based on IgG* (%) 93.33% GMT based on IgG* 952.67 (707.9, 1282.0) $ GMFR based on IgG* 136.09 (101.11, 183.1) $ *by S1 antigen ELISA $ data presented as Geometric Mean (95% CI) Interim Efficacy Data from Phase III Clinical Trial (2mg-3dose regimen with Pharmajet): A total of 27703 subjects were enrolled in the Phase III study till interim analysis. The interim primary efficacy analysis was based on the Per-Protocol analysis, which consisted of all participants with negative baseline SARS-CoV-2 status (i.e., negative RT-PCR for SARS- CoV-2) and who had received 3 doses of investigational product. Total of 12350 subjects who had completed 84±3 days in vaccine group and total 12320 subjects who had completed 84±3 days in placebo group were considered for analysis. Out of 81 symptomatic RT-PCR positive COVID-19 cases considered for interim analysis, 61 were in placebo group and 20 were in the vaccine (ZYCOV-D®) group. On the basis of calculation, ZYCOV-D® vaccine efficacy is 66.6% (95% CI: 47.6 to 80.7). Immunogenicity Data 28 days after second dose from Phase III Clinical Trial (3mg-2dose regimen with Pharmajet) in subjects seronegative at baseline: Parameter Total Adults Adolescents Seroconversion rate based on 95.3% 96.3% 96.3% IgG* (%) GMT based on IgG* 1262.9 1088.2 1465.7 (960.0 to 1661.4) (736.2 to 1608.5) (990.3 to 2169.3) GMFR based on IgG* 180.4 155.5 209.4 (137.2 to 237.4) (105.2 to 229.8) (141.5 to 309.9) *by S1 antigen ELISA $ data presented as Geometric Mean (95% CI) 5.3 Pharmacokinetic properties • Not applicable Page 10 of 136. Preclinical safety data 6.1 Animal Pharmacology: The immunogenicity potential of ZYCOV-D® has been evaluated in mice, guinea pig and rabbit models by intradermal route at varying dose levels. Immunogenicity studies in animals demonstrated that the candidate DNA vaccine induces robust antibody response including neutralizing antibodies against SARS-CoV-2 and also provided Th-1 response as evidenced by elevated IFN-γ levels. In animal studies primary antibody response starts mounting in serum two weeks after two doses and reaches peak two weeks after third immunization. The serum IgG levels against spike antigen in mice were maintained even after three months post last dosing suggesting a long-term immune response generated by the DNA vaccine candidate. Protective efficacy of ZYCOV-D® was also evaluated in Rhesus Macaques. We assessed the immunogenicity and protective efficacy of two formulations (1mg and 2mg) of ZYCOV-D® administered either through Needle Free Injection System (NFIS) and syringe needle (intradermal) with three dose vaccine regimens. ZYCOV-D® demonstrated good immunogenicity as can be seen by the analysis of SARS-CoV-2 specific IgG (S1), Neutralizing Antibody (Nab) titres, percentage lymphocytes and cytokines response during immunization and after virus challenge. The viral clearance in nasal swab (NS), throat swab (TS), and bronchoalveolar lavage (BAL) in animals receiving ZYCOV-D® was seen demonstrating protective efficacy. 6.2 Animal Toxicology Non-clinical data reveal no special hazard for humans based on a conventional study of repeat dose toxicity. Animal studies evaluating potential toxicity to reproduction and development have not yet been completed. 28-day repeat dose preclinical toxicology (PCT) studies were conducted in Wistar rats and New Zealand white rabbits and the vaccine was found to be safe and well-tolerated. Indeed, no treatment related adverse effects and behavioral changes were observed in animals during the studies. Further, histopathological examination reveals no changes of toxicological significance at high dose of 3mg (1.5 times the intended single human dose) and 6mg (3 times the intended single human dose) in rats and rabbits respectively. Page 11 of 137. Description ZYCOV-D® is a DNA based vaccine for prevention of COVID-19. It comprises of a DNA plasmid vector carrying full length spike (S) gene region expressing SARS-CoV-2 spike (S) protein along with gene coding for signal peptide. The spike gene region was selected from submitted Wuhan Hu-1 isolate sequence (Genebank Accession No. MN908947.3). The S protein of the virus includes the receptor binding domain (RBD), responsible for binding to the human angiotensin converting enzyme-2 (ACE-2) receptor, which mediates the entry of virus inside the cell. The DNA plasmid construct was transformed into E. coli cells for large scale production. 8. PHARMACEUTICAL PARTICULARS 8.1 List of excipients Not Applicable, as no excipient is being used. 8.2 Incompatibilities This vaccine should not be mixed with any other medicinal product. 8.3 Shelf life The expiry date of vaccine is indicated on the label and packaging. Once opened, multi-dose vials should be used as soon as practically possible and within 6 hours when kept between +2ºC and +8ºC. All opened multidose vials of ZYCOV-D® should be discarded at the end of immunization session or within 6 hours whichever comes first. 8.4 Special precautions for storage Store at 2° to 8°C. Do Not Freeze. In case of unexpected freezing of vaccine at 2-8ºC storage, it can be administered after thawing. Multidose Vials: To be used within 6 hours of opening. 8.5 Packing information ZYCOV-D® is supplied in a USP type-1 tubular glass vial 2.0 ml. Page 12 of 138.6 Special precautions for disposal Any unused product or waste material should be disposed of in accordance with local requirements. 9. Details of manufacturer Zydus Lifesciences Limited (formerly known as Cadila Healthcare Limited) Plot Survey No. 23, 25/P, 37, 40/P, 42 to 47 Sarkhej- Bavla N.H. 8A, Opp. Ramdev Masala, Village: Changodar, Taluka: Sanand, Dist. Ahmedabad – 382 213 Phone: +91-2717- 664600 10. MARKETING AUTHORISATION NUMBER(S) MF/BIO/22/000034 11. DATE OF FIRST AUTHORISATION 25-Apr-2022 Page 13 of 13WHAT IF I DECIDE NOT TO GET ZYCOV-D® VACCINE? It is your choice to receive or not receive ZYCOV-D® Vaccine. You may prefer to consult your healthcare FACT SHEET FOR VACCINE RECIPIENT provider. CAN I RECEIVE ZYCOV-D® VACCINE WITH CAUTION OTHER VACCINES? 3mg – 2 Dose Regimen: 3 shots of 0.1ml each should be given There is no information on the use of ZYCOV-D® on day 0 and 28 Vaccine with other vaccines. WHAT IF I AM PREGNANT OR BREASTFEEDING? It is recommended to use the vaccine only with Pharmajet There is no clinical data on use of ZYCOV-D® Device. Using it with conventional needle and syringe Vaccine in pregnant and breastfeeding women. will not lead to optimal immunogenicity response and will You may discuss your options with the healthcare affect the efficacy of the vaccine. provider. APPROVED FOR RESTRICTED USE IN WILL ZYCOV-D® VACCINE GIVE ME COVID-19 EMERGENCY SITUATION OF INFECTION? No. ZYCOV-D® Vaccine does not contain SARS- Novel Corona Virus 2019 - nCoV CoV-2 virus and cannot give you COVID-19 infection. Vaccine (Recombinant) KEEP YOUR VACCINATION CARD ZYCOV-D® When you get your dose, please discuss with your IN PREVENTION OF COVID-19 DISEASE healthcare provider regarding the option of your IN INDIVIDUALS 12 YEARS OF AGE AND OLDER vaccination record on digital platform, if available. This vaccine has been given restricted use HOW CAN I LEARN MORE? license for emergency situation. It does not have • Ask the healthcare provider. a marketing authorization, however, this approval • Contact your local or state public health for the restricted use in emergency situation department. grants permission for the vaccine to be used • for active immunization of individuals aged 12 For further details on vaccine and answers to years and older for the prevention of coronavirus frequently asked questions, kindly visit www. disease 2019 (COVID-19). zycovd.co.in Reporting of side effects Manufactured & Marketed by: As with any new vaccine, this vaccine will be Zydus Lifesciences Limited closely monitored to allow quick identification of (formerly known as Cadila Healthcare Limited) new safety information. You can help by reporting Plot Survey No.: 23, 25/P, 37, 40/P, 42 to any side effects to Zydus Lifesciences Limited 47, Sarkhej-Bavla N.H. No. 8A, Changodar, who is the manufacturer of ZYCOV-D® vaccine on toll free number 1800 419 1141 or visit www. Tal: Sanand, Dist.: Ahmedabad-382213, zyduslife.com Gujarat For information on vaccine For more information read this fact sheet carefully. For further details on vaccine and answers to frequently asked questions, kindly visit www. zycovd.co.in To report adverse events, call toll free on Follow the link for video demonstration of 1800 419 1141 or visit www.zyduslife.com Pharmajet Tropis Device and method of administration: http://zycovd.co.in/needle-free- ® Registered Trademark injector-system/medication-guide-video/ or scan the QR code: QR CODE for Video Demo You are being offered ZYCOV-D® Vaccine of Zydus Lifesciences Limited to prevent Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2. This Fact Sheet contains information to help you understand the risks and benefits of ZYCOV-D® Vaccine, which you may receive because there is currently a pandemic of COVID-19 disease. ZYCOV-D® is a vaccine and may prevent you from getting COVID-19 disease. ZYCOV-D® vaccination has been approved for use as 2 separate doses of 0.3ml each to be given at an interval of 28 days(day 5063802 Downloaded from ZyArts. Downloaded by Nagendra M Soni on 20/07/2022 05:27:20 PM Date.:14.06.22 \\sigma-file-clu\ptc packaging\Design Studio\01 Artworks Store\Domestic\01 Zydus Lifesciences\ ZLL\Zycov-D Vaccine\2083605_LIT. Zycov-D Vaccine 2ml Vial SL DOM\2083605 Page : 1 of 2 3x0.1 ml 3x0.1 ml Day 0 Day 28Date.:14.06.22 \\sigma-file-clu\ptc packaging\Design Studio\01 Artworks Store\Domestic\01 Zydus Lifesciences\ ZLL\Zycov-D Vaccine\2083605_LIT. Zycov-D Vaccine 2ml Vial SL DOM\2083605 Page : 2 of 2 0 and day 28). Each dose consists of three shots of ZYCOV-D® vaccination course consists of 2 0.1ml each given by needle free injector (Pharmajet separate doses of 3mg each. Tropis device) via intradermal route at three If you receive one dose of ZYCOV-D® vaccine, then separate sites (2 shots on one arm (recommended the 2nd dose should be administered 28 days after the previous dose. distance between two shots is at least 5 cms) and 1 If you miss your 2nd dose shot on other arm). If you forget to go back at the scheduled time, ask ZYCOV-D® vaccine has shown efficacy of 66.6% your healthcare provider for advice. It is important in interim analysis of Phase III clinical trial with 2 that you return for your 2nd dose of ZYCOV-D® mg - 3dose regimen. This vaccine may not protect vaccine as per your dosing regimen. everyone. HAS ZYCOV-D® VACCINE BEEN USED BEFORE? WHAT YOU NEED TO KNOW BEFORE YOU GET ZYCOV-D® is being used in clinical trials, a number of participants have received one or two or THIS VACCINE three doses in trials being conducted in India. WHAT IS COVID-19? WHAT ARE THE BENEFITS OF ZYCOV-D® COVID-19 disease is caused by a coronavirus called SARS-CoV-2. This type of coronavirus has VACCINE? not been seen before. You can get COVID-19 In ongoing clinical trials, ZYCOV-D® Vaccine has through contact with another person who has the been shown to prevent COVID-19 disease following virus. It is predominantly a respiratory illness that 3 doses of 2mg each given 28 days apart. The can affect other organs. People with COVID-19 duration of protection against COVID-19 disease is have had a wide range of symptoms reported, currently unknown. ranging from mild symptoms to severe illness. Symptoms may appear 2 to 14 days after exposure You may get protective immune response 28 days to the virus. Symptoms may include: fever or chills; after the 3rd dose of 2mg - 3 dose regimen of cough; shortness of breath; fatigue; muscle or ZYCOV-D® vaccine. Similar immune response is body aches; headache; new loss of taste or smell; also seen 28 days after 2nd dose of 3mg - 2 dose sore throat; congestion or runny nose; nausea or regimen of ZyCoV-D vaccine. The comparison of vomiting; diarrhea. immune response of 2mg - 3 dose regimen and WHAT IS ZYCOV-D® VACCINE? 3mg - 2 dose regimen is shown in table below: ZYCOV-D® is approved for restricted use in Table: Immunogenicity Data in subjects emergency situation vaccine that may prevent seronegative at baseline: COVID-19 disease in individuals 12 years of age and older. Day 56 Data of 3mg - Day 84 data of 2mg Statistics Cohort 2 dose regimen – 3 dose regimen WHAT SHOULD YOU MENTION TO YOUR 122 / 128 168 / 180 HEALTHCARE PROVIDER BEFORE YOU GET Total (95.3%) (93.3%) ZYCOV-D® VACCINE? Seroconversion 61/64 132/142 Tell the healthcare provider about all of your rate based on Adults (95.3%) (93.0%) IgG* (%) medical conditions, including: 61/64 36/38 • Pediatric If you have ever had a severe allergic reaction (95.3%) (94.7%) (anaphylaxis) after any drug, food, any vaccine 1262.9 998.1 Total or any ingredients of ZYCOV-D® vaccine (960.0 to 1661.4) (778.7 to 1279.3) • If you have fever GMT based on 1088.2 926.0 • If you have a bleeding disorder or are on a blood IgG* Adults (736.2 to 1608.5) (693.9 to 1235.9) thinner Pediatric 1465.7 1320.9 • If you are immunocompromised or are on a (990.3 to 2169.3) (816.4 to 2137.1) *by S1 antigen ELISA medicine that affects your immune system • $ data presented as Geometric Mean (95% CI) If you are pregnant or plan to become pregnant • WHAT ARE THE RISKS OF ZYCOV-D® VACCINE? If you are breastfeeding • Common side effects that have been reported with If you have received another COVID-19 vaccine ZYCOV-D® Vaccine include: You should consult your healthcare provider before • Injection site redness deciding to take the vaccine. • Injection site pain WHO SHOULD GET ZYCOV-D® VACCINE? • Injection site itching ZYCOV-D® Vaccine has been approved for • Injection site swelling restricted use in emergency situation in individuals 12 years of age and older. • Fever • Muscle Pain WHO SHOULD NOT GET ZYCOV-D® VACCINE? • Headache •Yo u should not get ZYCOV-D® Vaccine if you: • Nausea had a severe allergic reaction after a previous • Fatigue / Tiredness • dose of this vaccine • Diarrhea had a severe allergic reaction to any ingredient These may not be all the possible side effects of of this vaccine ZYCOV-D® Vaccine. Serious and unexpected side • had a severe allergic reaction to any other effects may occur. ZYCOV-D® Vaccine is still being vaccine studied in clinical trials. WHAT ARE THE INGREDIENTS IN ZYCOV-D® WHAT SHOULD I DO ABOUT SIDE EFFECTS? VACCINE? If you experience a severe allergic reaction, call or ZYCOV-D® Vaccine includes the following go to the nearest hospital. ingredients: Deoxyribonucleic acid (DNA) Call the healthcare provider if you have any side Phosphate buffered saline effects that bother you or do not go away. In addition, you can report side effects after HOW IS ZYCOV-D® GIVEN? vaccination to Zydus Lifesciences Limited who is ZYCOV-D® Vaccine will be given to you as an the manufacturer of ZYCOV-D® vaccine on toll free Intradermal (ID) injection only using Needle Free number 1800 419 1141 or visit www.zyduslife.com Injector (Pharmajet Tropis device).3063802 Downloaded from ZyArts. Downloaded by Nagendra M Soni on 20/07/2022 05:28:45 PM Date.:14.06.22 \\sigma-file-clu\ptc packaging\Design Studio\01 Artworks Store\Domestic\01 Zydus Lifesciences\ ZLL\Zycov-D Vaccine\2083603_PI Zycov-D Vaccine 2ml Vial SL DOM\2083603 Page : 1 of 2 group and 20 were in the vaccine (ZYCOV-D®) group. On the basis of calculation, ZYCOV-D® vaccine efficacy is 66.6% (95% CI: 47.6 to 80.7). Immunogenicity Data 28 days after second dose from Phase III Clinical Trial (3mg-2dose regimen with Pharmajet) in subjects seronegative at baseline: Approved for restricted use in emergency situation of COVID-19. Parameter Total Adults Adolescents F lao br o t rh ae to u rys e o no lf y a . Registered Medical Practitioner or a Hospital or a Seroconversion rate based on IgG* (%) 95.3% 95.3% 95.3% GMT based on IgG* (960.1 02 to62 1. 69 6 1.4) (736.1 2 0 t8 o8 1.2 6 08.5) (990.1 3 4 t6 o5 2.7 1 69.3) CAUTION GMFR based on IgG* (137.1 28 to0 .4 23 7.4) (105.1 2 5 t5 o. 5 2 29.8) (141.2 5 0 t9 o. 4 3 09.9) 3mg – 2 Do 3s xe 0 .R 1 e mg L imen: 3 shots of 0.1mL each 3 xs 0h .1o mul Ld be given on day 0 and 28 Day 0 Day 28 *by S1 antigen ELISA $ data presented as Geometric Mean (95% CI) It is recommended to use the vaccine only with Pharmajet Device. 5.3 Pharmacokinetic properties Using it with conventional needle and syringe will not lead to optimal NA immunogenicity response and will affect the efficacy of the vaccine. 6. Nonclinical properties 1. Name of Medicinal Product 6.1 Animal Pharmacology The immunogenicity potential of ZYCOV-D® has been evaluated in mice, Novel Corona Virus 2019 - nCoV Vaccine g Imu mine ua n op gig e na in cd it yr a sb tb ui dt im eso d ie nl s a b ny im in atr lsa d de erm ma ol n r so tu rate te a dt v tha ary t in tg h ed o cs ae n l de iv de al ts e. (Recombinant) DNA vaccine induces robust antibody response including neutralizing ZYCOV-D® antibodies against SARS-CoV-2 and also provided Th-1 response as evidenced by elevated IFN-γ levels. In animal studies primary antibody 2. Qualitative and quantitative composition response starts mounting in serum two weeks after two doses and Each 0.1 mL contains: reaches peak two weeks after third immunization. The DNA plasmid construct with spike protein gene region serum IgG levels against spike antigen in mice were maintained even from SARS-CoV-2 virus Produced in E.coli 1.0 mg after three months post last dosing suggesting a long-term immune Phosphate Buffered saline q.s. response generated by the DNA vaccine candidate. 3. Dosage form and strength Protective efficacy of ZYCOV-D® was also evaluated in Rhesus Solution for Intradermal Injection. Macaques. We assessed the immunogenicity and protective efficacy Each dose consists of three shots of 0.1 mL each of two formulations (1mg and 2mg) of ZYCOV-D® administered 4. Clinical particulars either through Needle Free Injection System (NFIS) and syringe 4.1 Therapeutic indication needle (intradermal) with three dose vaccine regimens. ZYCOV-D® ZYCOV-D® is indicated for active immunisation to prevent COVID-19 demonstrated good immunogenicity as can be seen by the analysis caused by SARSCoV-2 in individuals 12 years of age and older when of SARS-CoV-2 specific IgG (S1), Neutralizing Antibody (NaB) titres, given in two separate doses of 3mg (0.3ml) each to be given at an percentage lymphocytes and cytokines response during immunization interval of 28 days each (day 0, day 28). ZYCOV-D® is approved for and after virus challenge. The viral clearance in nasal swab (NS), throat restricted use in emergency situation of COVID-19. swab (TS), and bronchoalveolar lavage (BAL) in animals receiving 4.2 Posology and method of administration ZYCOV-D® was seen demonstrating protective efficacy. This vaccination schedule consists of 2 separate doses to be given at 6.2 Animal Toxicology an interval of 28 days each (day 0 and day 28). Each 3mg dose consists Non-clinical data reveal no special hazard for humans based on a of three shots of 0.1mL each given by needle free injector (Pharmajet conventional study of repeat dose toxicity. Animal studies evaluating Tropis device) via intradermal route at three separate sites (2 shots on potential toxicity to reproduction and development have not yet been one arm (recommended distance between two shots is at least 5 cms) completed. and 1 shot on other arm). 28-day repeat dose preclinical toxicology (PCT) studies were conducted Method of Administration: in Wistar rats and New Zealand white rabbits and the vaccine was found ZYCOV-D® has to be given by intradermal route only using needle free to be safe and well-tolerated. Indeed, no treatment related adverse injector (Pharmajet Tropis device). effects and behavioural changes were observed in animals during the Kindly refer Medication Guide for step by step guidance on studies. Further, histopathological examination reveals no changes of Method of Administration toxicological significance at high dose of 3mg (1.5 times the intended 4.3 Contraindications single human dose) and 6mg (3 times the intended single human dose) ZYCOV-D® is contraindicated in individuals known to have in rats and rabbits respectively. hypersensitivity to the active substance or to any of the excipients 7. Description 4.4 Special warnings and precautions for use ZYCOV-D® is a DNA based vaccine for prevention of COVID-19. It Hypersensitivity comprises of a DNA plasmid vector carrying full length spike (S) gene As with all injectable vaccines, appropriate medical treatment and region expressing SARS-CoV-2 spike (S) protein along with gene coding supervision should always be readily available in case of an anaphylactic for signal peptide. The spike gene region was selected from submitted event following the administration of the vaccine. Wuhan Hu-1 isolate sequence (Genebank Accession No. MN908947.3). Concurrent Illness The S protein of the virus includes the receptor binding domain (RBD), As with other vaccines, administration of ZYCOV-D® should be responsible for binding to the human angiotensin converting enzyme-2 postponed in individuals suffering from an acute severe febrile illness. (ACE-2) receptor, which mediates the entry of virus inside the cell. The However, the presence of a minor infection, such as cold, and/or low DNA plasmid construct was transformed into E. coli cells for large scale grade fever should not delay vaccination. production. Immunocompromised individuals 8. Pharmaceutical particulars It is not known whether individuals with impaired immune responsiveness, 8.1 Incompatibilities including individuals receiving immunosuppressant therapy, will elicit This vaccine should not be mixed with any other medicinal product. the same response as immunocompetent individuals to the vaccine 8.2 Shelf-life regimen. Immunocompromised individuals may have relatively weaker The expiry date of vaccine is indicated on the label and packaging. Once immune response to the vaccine regimen. opened, multi-dose vials should be used as soon as practically possible Duration and level of protection and within 6 hours when kept between +2ºC and +8ºC. All opened The duration of protection has not yet been established. As with any multidose vials of ZYCOV-D® should be discarded at the end vaccine, vaccination with ZYCOV-D® may not protect all vaccine of immunization session or within 6 hours whichever comes first. recipients. 8.3 Packaging information Interchangeability ZYCOV-D® is supplied in a USP type-1 tubular glass vial 2.0 mL. No data are available on the use of ZYCOV-D® in persons that have 8.4 Storage and handing instructions previously received partial / complete vaccine series with another Store at 2° to 8°C. Do Not Freeze. In case of unexpected freezing of COVID-19 vaccine. vaccine at 2-8ºC storage, it can be administered after thawing. 4.5 Interactions Multidose Vials: To be used within 6 hours of opening No interaction studies have been performed. Concomitant administration 9. Details of manufacturer of ZYCOV-D® with other vaccines has not been studied Zydus Lifesciences Limited 4.6 Use in special populations (such as pregnant women, lactating (formerly known as Cadila Healthcare Limited) women, paediatric patients, geriatric patients etc.) Plot Survey No.: 23, 25/P, 37, 40/P, 42 to 47, Elderly Population: Sarkhej-Bavla N.H. No. 8A, Changodar, Tal: Sanand, Efficacy and safety data are currently limited in individuals ≥ 60 years Dist.: Ahmedabad-382213, Gujarat of age. No dosage adjustment is required in elderly individuals ≥ 60 years of age. 1 M0 F. /BD Ie Ot /a 2i 2ls /0 o 0f 0 p 0e 3r 4m Dis as teio dn 2 5o -r A l pic re -2n 0c 2e 2 number with date P Ea ffie cd ai ca ytr i ac n P do sp au fl ea tt yio dn a: ta are currently limited in adolescents aged 12 to 11. Date of revision <18 years. The safety and efficacy of ZYCOV-D® in children (aged <12 13/06/2022 years old) has not yet been established. Fertility There is no clinical data on the effect of ZYCOV-D® on fertility. Pregnancy The safety and efficacy of ZYCOV-D® in pregnancy has not been To report adverse events, call toll free on established. 1800 419 1141 or visit www.zyduslife.com Breastfeeding ® Registered Trademark The safety and efficacy of ZYCOV-D® in lactating females has not been established. 4.7 Effects on ability to drive and use machines ZYCOV-D® has no or negligible influence on the ability to drive and use machines. However, some of the adverse reactions may temporarily affect the ability to drive or use machines. 4.8 Undesirable effects Phase I/II Study: A total of 1048 subjects were enrolled in the Phase I/II study, comprising of 4 different arms as follows: • Arm 1: 1mg dose given by needle and syringe • Arm 2: 1mg dose given by Pharmajet • Arm 3: 2mg dose given by needle and syringe • Arm 4: 2mg dose given by Pharmajet The age group and demographic characteristics of the subjects enrolledDate.:14.06.22 \\sigma-file-clu\ptc packaging\Design Studio\01 Artworks Store\Domestic\01 Zydus Lifesciences\ ZLL\Zycov-D Vaccine\2083603_PI Zycov-D Vaccine 2ml Vial SL DOM\2083603 Page : 2 of 2 in Phase I/II study are as follows: Solicited Systemic Adverse Events: The most commonly reported solicited Phase I: 48 adult subjects systemic adverse events across all treated subjects in both groups Arm 1, 1 mg Arm 2, 1 mg Arm 3, 2 mg Arm 4, 2 mg (ZYCOV-D® and Placebo) were headache (0.25% and 0.22% after Dose 1; (0.1 mL needle (0.1 mL (0.2 mL needle (0.2 mL 0.20% and 0.24% after Dose 2 and 0.16% and 0.17% after Dose 3), fever and syringe) Pharmajet) and syringe) Pharmajet) (0.20% and 0.14% after Dose 1; 0.14% and 0.21% after Dose 2 and 0.13% Adult subjects (Male) 12 12 12 12 and 0.10% after Dose 3), muscle pain (0.19% and 0.28% after Dose 1; 0.11% and 0.18% after Dose 2 and 0.11% and 0.09% after Dose 3), and Mean Age (Years) 35.4 31.8 35.1 37.2 fatigue (0.19% and 0.19% after Dose 1; 0.14% and 0.16% after Dose 2 and Phase II: 1000 subjects 0.09% and 0.13% after Dose 3). Most of the adverse events were mild or Arm 1, 1 mg Arm 2, 1 mg Arm 3, 2 mg Arm 4, 2 mg moderate in severity. These events were comparable between ZYCOV-D® (0.1 mL needle (0.1 mL (0.2 mL needle (0.2 mL and placebo groups. and syringe) Pharmajet) and syringe) Pharmajet) Unsolicited Adverse Events: Arthralgia, Back pain, Muscle spasms, N 251 249 250 250 Myalgia, Musculoskeletal pain, Neck pain, Vertigo, Diarrhoea, Gastritis, Male 188 186 179 177 Gastrooesophageal reflux disease, Nausea, Vomiting, Asthenia, Chills, Female 63 63 71 73 Eye irritation, Abdominal distension, Abdominal pain, Fatigue, Pain, Adolescent 04 06 06 02 Pyrexia, Nasopharyngitis, Pain in extremity, Ageusia, Anosmia, Cerebral Mean Age (Years) 35.0 ± 11.83 34.2 ± 12.11 35.4 ± 10.46 34.6 ± 10.43 infarction, Dizziness, Headache, Cough, Dyspnoea, Nasal dryness, Adverse events reported in Phase I Study with 2mg Pharmajet Arm: Oropharyngeal pain, Rhinorrhoea, Sneezing. Solicited adverse events: Tenderness at the site of injection. Serious adverse events: As per interim analysis report, 15 serious adverse Unsolicited adverse events: Low WBC count. events were identified: stroke (02), Death due to Cardiorespiratory arrest Adverse events reported in Phase II Study with 2mg Pharmajet Arm: with septicaemia and alcoholic liver disease (1), Death due to COVID19 Solicited adverse events: Nausea, fatigue, injection site erythema, (1), Gram negative enteritis (1) and COVID19 (10). None of these serious injection site pain, injection site pruritus, injection site swelling, pyrexia, adverse events was related to IP. myalgia and headache. Adverse Events reported from Phase I/II Study - 3mg-2dose regimen: Frequency and Percentages of Participants with Solicited Local A total of 150 adults healthy subjects >18 years of age were enrolled in and systemic adverse events and Unsolicited adverse events after the Phase I/II study of 3mg – 2 dose regimen (100 in Vaccine arm and 50 each dose – Safety population in the Placebo arm). ZyCoV-D n(%) Placebo n(%) The age group and demographic characteristics of the subjects enrolled in Phase I/II study are as follows: Dose I Dose II Dose III Dose I Dose II Dose III AE Terms (N = 200) (N = 197) (N = 194) (N = 50) (N = 49) (N = 48) Vaccine (N = 100) Placebo (N = 50) n(%) n(%) n(%) n(%) n(%) n(%) Mean Age (years) 34.2 36.7 Solicited Local AEs Male 68 (68.0%) 30 (60.0%) Pain at injection site 7 (3.50) 9 (4.57) 6 (3.09) 0 (0.00) 0 (0.00) 0 (0.00) Female 32 (32.0%) 20 (40.0%) Redness at injection site 9 (4.50) 10 (5.08) 9 (4.64) 0 (0.00) 0 (0.00) 0 (0.00) The following adverse events were reported during the study: Swelling at injection site 5 (2.50) 6 (3.05) 5 (2.58) 0 (0.00) 0 (0.00) 0 (0.00) Local site adverse events: Pain (1.9%), Redness (1.4%), Swelling Itching at injection site 1 (0.50) 7 (3.55) 2 (1.03) 0 (0.00) 0 (0.00) 0 (0.00) (1.2%), Itching (0.5%) Systemic adverse events: Headache (2.6%), Tiredness / Fatigue (2.1%), Muscle pain 1 (0.50) 0 (0.00) 1 (0.52) 0 (0.00) 0 (0.00) 0 (0.00) Fever (1.1%), Diarrhea (0.5%) and Nausea (0.5%) Solicited Systemic AEs Adverse Events reported from Phase III Study - 3mg-2dose regimen: Fatigue 3 (1.50) 1 (0.51) 0 (0.00) 0 (0.00) 0 (0.00) 1 (2.08) In our ongoing Phase III clinical trial of 3mg – 2 dose regimen, a total of 3000 Fever 2 (1.00) 1 (0.51) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) healthy subjects >12 years of age have been enrolled. Amongst them 1193 Headache 3 (1.50) 1 (0.51) 0 (0.00) 1 (2.00) 0 (0.00) 1 (2.08) subjects belonged to the adolescent age group (12-17 years). Nausea 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) 1 (2.08) The age group and demographic characteristics of the subjects enrolled in Un Solicited Systemic AEs Phase III study are as follows: Covid-19 2 (1.00) 0 (0.00) 2 (1.03) 0 (0.00) 0 (0.00) 1 (2.08) Total Adults Adolescents Nasal Dryness 1 (0.50) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) (N = 3000) (N = 1807) (N = 1193) High Blood Pressure 1 (0.50) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Mean Age (years) 27.4 35.9 14.6 Arthralgia 0 (0.00) 1 (0.51) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Male 1907 (63.6%) 1278 (70.7%) 629 (52.7%) Body ache 0 (0.00) 3 (1.52) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Female 1093 (36.4%) 529 (29.3%) 564 (47.3%) Chikungunya virus infection 0 (0.00) 1 (0.51) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) The safety profile of the adolescent age group and the adult population has been found to be similar. The adverse events reported in total population Cough 0 (0.00) 2 (1.02) 1 (0.52) 0 (0.00) 0 (0.00) 0 (0.00) upto day 112 are as under: Pyrexia 0 (0.00) 5 (2.54) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Local site adverse events: Pain (1.9%), Redness (0.7%), Swelling (0.4%), Headache 0 (0.00) 2 (1.02) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Itching (0.3%) Myalgia 0 (0.00) 1 (0.51) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Solicited systemic adverse events: Headache (0.4%), Tiredness / Fatigue Rhinorrhoea 0 (0.00) 1 (0.51) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) (0.2%), Fever (0.4%), arthralgia (0.2%), myalgia (0.1%) and vomiting (0.01%). Asthenia 0 (0.00) 1 (0.51) 0 (0.00) 0 (0.00) 0 (0.00) 0 (0.00) Unsolicited systemic adverse events: Body ache (0.13%), Weakness (0.12%), Dysuria 0 (0.00) 0 (0.00) 1 (0.52) 0 (0.00) 0 (0.00) 0 (0.00) Headache (0.08%), Cough and Cold (0.08%), Fever (0.07%), Diarrhoea (0.05%), Tiredness (0.03%), COVID-19 (0.06%), Myalgia (0.01%) and Fatigue 0 (0.00) 0 (0.00) 1 (0.52) 0 (0.00) 0 (0.00) 0 (0.00) Vomiting (0.01%) N = number of subjects in the specified treatment arm; n = Number of participants with the specified event 4.9 Overdose Serious adverse events: 4 subjects experienced 7 serious adverse Experience of overdose is limited. events: viral pneumonia, in-patient hospitalization [due to discharge at There is no specific treatment for an overdose with ZYCOV-D® In the elbow site, pyrexia, arthralgia, joint swelling, erythema], surgical removal event of an overdose, the individual should be monitored and provided of orthopaedic implant, acute coronary syndrome, left ventricular failure with symptomatic treatment as appropriate. with bronchopneumonia, and COVID-19 (02). None of these serious adverse events was related to IP. 5. Pharmacological properties A s A ( I e b TnIe n en hl d l q o r lt ev oe ot u ue h n ar le r lr ie e g gmsl o a d e ee na e dd g td gE. ia l tov rlv ot oe iae tn uhr t)n g hs p: et e e s P ai n ahre ne t dav dep ose r do i len m e er t t sIs m e I caI d e or c ne n glf aip r n t rlo y ao i am c sr pgat i he s elP i.d t c h gr A i ca ri a mn o hs l , u ae o P a p r nh I a tI g (oa I c1 sts tS 2ta ee t -l rtu 1h io sI d 7e/ f tI y i mI 2 cy - s7 es m2 7t a ou m 0 r fod s 3 trgi ) he e .s- es 3 u t hd sbr aoe uje nss bce o jet 9 l srv c0 ee h t0 sgd a i s em vw ue ne b i rbt n ojh ee lo lce eu tn dst e g p w b f c5 T o en e r y. h i l1 o l d lt t le lp e t t sei de nM lp r a dis i tg rl n osae e h m i sc ct nio trnmh t r a i s adt ta ie ni t th n-d sn g s tc e s r ci lre a a ls na oo sl ntlm at y cn s ie so tn a,s ifd n vo et twt h er ecf u mh i e n tA c tee s c hatt oc dr i o ec seo t nh ci f t oio pfh i etZ on f rn er lY re olte s m hr tC m h ey e i as,O o i a nt as t iiV l ,ohn int k - ne us tD ec i . sg li ie® yn n ue F l c s al n tt u oa h e l D r li y r e r tt br htN ey en e teAi od nun re . ccg c tx to hl hT let po d eh ehu rn e e e us ce s ss ss ea d . is p g ls T leui ug n k h da s le ae ae in n ln w- r S e pge pi mt r p ehg i ot ni epie hs t n e mtn o e t iih dte m n bhe eh ro ee p ao ef ; r p n s c oi pwn rt e ed o it i s l .te c lu m h o Te ar co m pe l e n hlu ts ’ de d esstt in Phase III study are as follows: antigen is recognized by antigen presenting cells (APCs) and further Phase III: 27703 subjects (Data at the time of interim analysis), Total sample size: 28216 induces antibodies including neutralizing antibodies and cellular immune (0.V 2a mcc Li n Pe h, a 2 r mm ag jet) Placebo Total r 5e .2sp Pon hs ae r mth aro cu og dh y nm aa mjo icr h pis roto pc eo rm tiep satibility complex (MHC). Age (in Years) Mean 36.4 36.6 36.5 Immunogenicity Data 28 days after last dose from Phase II and Phase Age (12-17) 448 487 935 III Clinical Trials (2mg-3dose regimen with Pharmajet): Phase II Clinical Trial: Age ( 18-60) 12364 12338 24702 Parameter Data Age (above 60) 1039 1027 2066 Seroconversion rate based on IgG* (%) 91.28% Gender Seroconversion rate based on Neutralizing Antibody response^ (%) 88.89% Female 4506 4605 9111 GMT based on Neutralizing Antibody response^ 131.32 (63.50, 271.58)$ Male 9345 9247 18592 GMFR based on Neutralizing Antibody response^ 22.56 (10.57, 48.16) $ Subjects at risk(Co-morbidities) 709 740 1449 *by S1 antigen ELISA Stable Chronic Heart Disease 167 155 322 ^Wild type virus neutralization assay (PRNT) Stable Chronic Lung Disease 13 7 20 $ data presented as Geometric Mean (95% C50I) Controlled Diabetic 275 289 564 Phase III Clinical Trial: Stable Liver Disease 2 3 5 Parameter Data Severe Obesity 18 14 32 Seroconversion rate based on IgG* (%) 93.33% Other Stable Co-morbid 295 293 588 GMT based on IgG* 952.67 (707.9, 1282.0) $ The safety profile of the adolescent age group and the overall population GMFR based on IgG* 136.09 (101.11, 183.1) $ has been found to be same. The common solicited and unsolicited adverse *by S1 antigen ELISA events reported in total population are as under: $ data presented as Geometric Mean (95% CI) Solicited Local Adverse Events: The most frequently reported solicited Interim Efficacy Data from Phase III Clinical Trial (2mg-3dose regimen local adverse events across all treated subjects in both groups (ZYCOV-D® with Pharmajet): and Placebo) were pain at injection site: (0.66% and 0.62% after Dose A total of 27703 subjects were enrolled in the Phase III study till interim 1; 0.34% and 0.35% after Dose 2 and 0.27% and 0.26% after Dose 3), analysis. The interim primary efficacy analysis was based on the Per- redness: (0.31% and 0.28% after Dose 1; 0.19% and 0.09% after Dose Protocol analysis, which consisted of all participants with negative 2 and 0.17% and 0.09% after Dose 3), swelling: (0.27% and 0.28% after baseline SARS-CoV-2 status (i.e., negative RT-PCR for SARS-CoV-2) Dose 1; 0.08% and 0.06% after Dose 2 and 0.09% and 0.05% after Dose and who had received 3 doses of investigational product. Total of 3) and itching: 0.08% and 0.14% after Dose 1; 0.05% and 0.07% after 12350 subjects who had completed 84±3 days in vaccine group and Dose 2 and 0.02% and 0.05% after Dose 3). Most of the adverse events total 12320 subjects who had completed 84±3 days in placebo group w ZYer Ce O m Vi -ld D ®o r a m ndo d pe lara cete b i on gs re ov ue pr sit .y . These events were comparable between w Ce Or Ve IDco -1n 9s id ce ar se ed s fo cor na sn ida ely rs ei ds. fO oru t i no tef r8 im1 s ay nm ap lyt so im s,a 6tic 1 R wT e- rP eC inR pp lo as ci eti bv oe