E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Healthy Volunteers, with or without comorbidities (Prevention of SARS-CoV-2-mediated COVID-19) |
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E.1.1.1 | Medical condition in easily understood language |
Healthy Volunteers, some of which may have an underlying medical condition (Prevention of COVID-19) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10084465 |
E.1.2 | Term | COVID-19 vaccination |
E.1.2 | System Organ Class | 100000004865 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the efficacy of Ad26.COV2.S in the prevention of molecularly confirmed, moderate to severe/critical COVID-19, as compared to placebo, in SARS-CoV-2 seronegative adults |
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E.2.2 | Secondary objectives of the trial |
- To demonstrate the efficacy of Ad26.COV2.S in the prevention of moderate to severe/critical COVID-19 in adults regardless of their serostatus - To evaluate the efficacy of Ad26.COV2.S in the prevention of moderate to severe/critical COVID-19 - To assess the effect of Ad26.COV2.S on: 1. COVID-19 requiring medical intervention 2. SARS-CoV-2 viral RNA load for moderate to severe/critical COVID-19 3. Mild COVID-19 4. COVID-19 as defined by the US FDA harmonized case definition 5. All molecularly confirmed symptomatic COVID-19 6. Occurrence of confirmed asymptomatic or undetected infections with SARS-CoV-2 - To assess the efficacy of Ad26.COV2.S in the prevention of SARS-CoV-2 infection - To evaluate safety in terms of SAEs, MAAEs, and MAAEs leading to study discontinuation - In a subset of participants, to evaluate the safety and reactogenicity (local & systemic AEs, unsolicited AEs), and immunogenicity of Ad26.COV2.S as compared to placebo |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Stages 1a and 2a: Participant is ≥18 to <60 years of age on the day of signing the ICF. Stages 1b and 2b: Participant is ≥60 years of age on the day of signing the ICF 2. Stage 1: In the investigator’s clinical judgement, participant must be either in good or stable health, including a BMI <30 kg/m2. Participants may have underlying illnesses (not associated with increased risk of progression to severe COVID-19 as specified in Exclusion Criteria), as long as their symptoms and signs are stable and well-controlled. If participants are on medication for a condition, the medication dose must have been stable for at least 12 weeks preceding the 1st vaccination and expected to remain stable for the duration of the study. Participants will be included on the basis of relevant medical history and BMI at screening. As of Stage 2: In the investigator’s clinical judgement, participant may have a stable and well-controlled comorbidity associated with an increased risk of progression to severe COVID-19 (eg, stable/well-controlled HIV infection). If participants are on medication for comorbidity associated with an increased risk of progression to severe COVID-19, the medication dose must have been stable for at least 12 weeks preceding the 1st vaccination and expected to remain stable for the duration of the study. Participants will be included on the basis of relevant medical history and BMI at screening. 3. Contraceptive (birth control) use should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies. 4. Participant agrees to not donate bone marrow, blood, and blood products from the first study vaccine administration until 3 months after the last dose of the study vaccine. |
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E.4 | Principal exclusion criteria |
1. Participant has a clinically significant acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature ≥38.0ºC (100.4°F) within 24 hours prior to the planned 1st dose of study vaccine; randomization at a later date is permitted at the discretion of the investigator and after consultation with the sponsor. 2. Participant has a known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or their excipients (including specifically the excipients of the study vaccine). 3. Participant has abnormal function of the immune system resulting from: a. Clinical conditions (eg, autoimmune disease, potential immune mediated disease or known or suspected immunodeficiency, chronic kidney disease [with dialysis]) expected to have an impact on the immune response of the study vaccine. Participants with clinical conditions stable under non-immunomodulator treatment (eg, autoimmune thyroiditis, autoimmune inflammatory rheumatic disease such as rheumatoid arthritis) may be enrolled at the discretion of the investigator. Non-immunomodulator treatment is allowed as well as steroids at a non-immunosuppressive dose or route of administration. b. Chronic (>10 days) or recurrent use of systemic corticosteroids within 6 months before administration of the 1st dose of study vaccine and during the study. A substantially immunosuppressive steroid dose is considered to be ≥2 weeks of daily receipt of 20 mg of prednisone or equivalent. Ocular, topical or inhaled steroids are allowed. c. Administration of antineoplastic and immunomodulating agents or radiotherapy within 6 months before administration of the 1st dose of study vaccine and during the study. 4. Participant received treatment with Ig in the 3 months or blood products in the 4 months before the planned administration of the 1st dose of study vaccine or has any plans to receive such treatment during the study. 5. Participant received or plans to receive: a. Licensed live attenuated vaccines – within 28 days before or after planned administration of the 1st or subsequent study vaccinations. b. Other licensed (not live) vaccines – within 14 days before or after planned administration of the 1st or subsequent study vaccinations. 6. Participant previously received a coronavirus vaccine. 7. Participant received an investigational drug (including investigational drugs for prophylaxis of COVID-19) or used an invasive investigational medical device within 30 days or received an investigational vaccine (including investigational Adenoviral-vectored vaccines) within 6 months before the planned administration of the 1st dose of study vaccine or is currently enrolled or plans to participate in another investigational study during the course of this study. 8. Participant is pregnant or planning to become pregnant within 3 months after the last dose of study vaccine. 9. Participant has a history of an underlying clinically significant acute or chronic medical condition or physical examination findings for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the wellbeing) or that could prevent, limit, or confound the protocol-specified assessments. 10. Stage 1: Participants with comorbidities that are or might be associated with an increased risk of progression to severe COVID-19 11. Stage 1: Participant has a history of malignancy within 1 year before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or other malignancies with minimal risk of recurrence). 12. Stage 1: Participant has a history of acute polyneuropathy (eg, Guillain-Barré syndrome). 13. Stage 1: Participant had surgery requiring hospitalization (defined as inpatient stay for longer than 24 hours or overnight stay), within 12 weeks before 1st vaccination, or will not have fully recovered from surgery requiring hospitalization, or has surgery requiring hospitalization planned during the time the participant is expected to participate in the study or within 6 months after the last study vaccine administration. 14. Stage 1: Participant has chronic active hepatitis B or hepatitis C infection per medical history |
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E.5 End points |
E.5.1 | Primary end point(s) |
First occurrence of molecularly confirmed, moderate to severe/critical COVID-19, with onset at least 14 days after the 2nd vaccination (Day 71) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Efficacy: First occurrence of molecularly confirmed, moderate to severe/critical COVID-19, with onset -1 day after the 1st vaccination -at least 14 days after the 2nd vaccination (Day 71) -14 days after the 1st vaccination (Day 15) Safety: Occurrence and relationship of SAEs (during the entire study), MAAEs (until 6 months after the last vaccination), and MAAEs leading to study discontinuation (during the entire study) for all participants Immunogenicity: -Analysis of antibodies binding to the SARS-CoV-2 S protein by ELISA -SARS-CoV-2 neutralization as measured by virus neutralization assay (VNA; wildtype virus and/or pseudovirion expressing SARS-CoV-2 S protein) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy: Day 2, day 15, day 71 Safety: throughout the study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Germany |
India |
Italy |
South Africa |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |