| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy Volunteers (Prevention of COVID-19) |
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| E.1.1.1 | Medical condition in easily understood language |
| Healthy Volunteers (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 |
Adults:
1. To assess the humoral immune response to 3 dose levels (5x10^10 virus particle (vp), 2.5x10^10 vp, 1.25x10^10 vp) of Ad26.COV2.S, administered intramuscularly (IM) as a 2-dose schedule at a 56-day interval, 28 days after Vaccination 2.
2. To assess the humoral immune response to 2 dose levels (1 x10^11 vp and 5x10^10 vp) of Ad26.COV2.S, administered IM as a single vaccination, 28 days after Vaccination 1.
3. To assess the humoral immune response to Ad26.COV2.S at the 5x10^10 vp dose level, administered IM as a 2-dose schedule at a 28-day and at an 84-day interval, 28 days after Vaccination 2.
4. To assess the safety and reactogenicity of Ad26.COV2.S, administered IM at several dose levels, as a 2-dose or a single-dose schedule.
Adolescents:
1. To assess the safety and reactogenicity of a single dose of Ad26.COV2.S, administered IM at the 2.5x10^10 vp dose level. |
|
| E.2.2 | Secondary objectives of the trial |
Adults:
1. To assess the anamnestic response to antigen presentation of Ad26.COV2.S at the 1.25x10^10 vp dose level, administered 4 months after Vaccination 2 (2-dose schedule) or 6 months after a Vaccination 1 (single-dose schedule), 7 days after antigen presentation.
2. To assess the safety and reactogenicity of antigen presentation of Ad26.COV2.S at the 1.25x10^10 vp dose level, administered 4 months after Vaccination 2 (2-dose schedule) or 6 months after a Vaccination 1 (single-dose schedule).
3. To assess the humoral immune response to Ad26.COV2.S across all groups, at all blood collection timepoints.
Adolescents:
1. To assess the humoral immune response to a single dose of Ad26.COV2.S at the 2.5x10^10 vp dose level, administered IM.
2. To assess the humoral immune response to Ad26.COV2.S at the 2.5x10^10 vp dose level, at all blood collection timepoints. |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Adults:
1. Participant is 18 to 55 years of age, inclusive, or 65 years of age or older on the day of signing the ICF.
2. Participant must have a body mass index (BMI) <30.0 kg/m2.
3. Participant 18 to 55 years of age, inclusive: Participant must be healthy, in the investigator’s clinical judgment, as confirmed by medical history, physical examination, and vital signs performed at screening, and must not have comorbidities related to an increased risk of severe COVID-19, except for smoking, which is allowed.
Participant 65 years of age and older: in the investigator’s clinical judgment, participant must be either in good or stable health. Participant may have underlying illnesses, as long as the symptoms and signs are medically controlled and not considered to be comorbidities related to an increased risk of severe COVID-19, except for smoking, which is allowed. If on medication for a condition, the medication dose must have been stable for at least 12 weeks preceding vaccination and expected to remain stable for the duration of the study. Participant will be included on the basis of physical examination, medical history, and vital signs.
4. All participants of childbearing potential must:
a. Have a negative highly sensitive urine pregnancy test at screening.
b. Have a negative highly sensitive urine pregnancy test immediately prior to each study vaccine administration.
5. Participant agrees to not donate bone marrow, blood, and blood products from the first study vaccine administration until 3 months after receiving the last dose of study vaccine.
Adolescents:
1.Participant is 12 to 17 years of age, inclusive, on the day of signing the ICF
2.Participant must be healthy, in the investigator’s clinical judgment, as confirmed by medical history, physical examination, and vital signs performed at screening, and must not have comorbidities related to an increased risk of severe COVID-19
3.Contraceptive (birth control) use by women
4.Participant agrees to not donate bone marrow, blood, and blood products from the first study vaccine administration until 3 months after receiving the last dose of study vaccine. |
|
| E.4 | Principal exclusion criteria |
Adults:
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 first 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 history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence).
3. 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).
4. Participant has abnormal function of the immune system.
5. Participant has a history of any neurological disorders or seizures including Guillain-Barré syndrome, with the exception of febrile seizures during childhood.
6. Participant has a history of chronic urticaria (recurrent hives), eczema or adult atopic dermatitis.
7. Participant received treatment with immunoglobulins in the 3 months or blood products in the 4 months before the planned administration of the first dose of study vaccine or has any plans to receive such treatment during the study.
8. Participant is a woman who is pregnant, breastfeeding, or planning to become pregnant within 3 months after the last dose of study vaccine.
9. Participant has chronic active hepatitis B or hepatitis C infection per medical history.
10. Participant previously received a coronavirus vaccine.
11. Participant has a positive diagnostic test result for past (serological testing) or current (PCR based viral RNA detection) SARS-CoV-2 infection at screening.
12. Participants with comorbidities that are or might be associated with an increased risk of progression to severe COVID-19, ie, participants with moderate-to severe asthma; chronic lung diseases such as chronic obstructive pulmonary disease (COPD) (including emphysema and chronic bronchitis), idiopathic pulmonary fibrosis and cystic fibrosis; diabetes (including type 1 or type 2); serious heart conditions, including heart failure, coronary artery disease, congenital heart disease, cardiomyopathies, and pulmonary hypertension or high blood pressure; obesity (BMI ≥ 30 kg/m2); chronic liver disease, including cirrhosis; sickle cell disease; thalassemia; cerebrovascular disease; neurologic conditions (dementia); end stage renal disease; organ transplantation; cancer;HIV Infection and other immunodeficiencies; hepatitis B infection and sleep apneea. This list is consistent with the list of conditions that increase the risk of progression to severe COVID-19 available at the CDC website at the time of writing of this protocol, except for smoking, which is allowed.
Applicable only to participants 65 years of age and older: Participants may have hypertension of mild severity as long as it is stable and medically controlled as defined by no change in medication over the past 6 months (except for issues of tolerability or use of similar drug with same mechanism of action, eg, thiazides, Beta blockers, Alpha blockers at the same effective dose).
13. Participant who is currently working in an occupation with a high risk of exposure to SARS-CoV-2 infection (eg, health care worker or emergency response personnel who work in close contact with SARS-CoV-2 infected patients) or considered at the investigator’s discretion to be at increased risk to acquire COVID-19 for any other reason.
14. Participant who has had a known exposure to an individual with confirmed COVID-19 or SARS-CoV-2 infection within the past 2 weeks.
15. History of confirmed SARS or MERS.
Adolescents:
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 first dose of study vaccine
2.Participant has a history of malignancy within 5 years before screening
3. Participants who required chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the study vaccination
4.Any serious, chronic, or progressive disease
5.Participant has obesity
6.Participant received treatment with immunoglobulins in the 3 months or blood products in the 4 months before the planned administration of the first dose of study vaccine or has any plans to receive such treatment during the study
7.Participant has chronic active hepatitis B or hepatitis C infection per medical history
8.Exposure to a person with confirmed COVID-19 or SARS-CoV-2 infection within the past 2 weeks
9.History of confirmed SARS or MERS |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Adults:
1a. Serological response to vaccination as measured by virus neutralization assay (VNA) titers and enzyme-linked immunosorbent assay (S-ELISA, ELISA Units/mL [EU/mL]), 28 days after Vaccination 2.
1b. Antibody geometric mean titers (GMTs) (VNA) and geometric mean concentrations (GMCs) (S-ELISA), 28 days after Vaccination 2.
2a. Serological response to vaccination as measured by VNA titers and ELISA (S-ELISA, EU/mL), 28 days after Vaccination 1.
2b. Antibody GMTs (VNA) and GMCs (S-ELISA), 28 days after Vaccination 1.
3a. Serological response to vaccination as measured by VNA titers and ELISA (S-ELISA, EU/mL), 28 days after Vaccination 2.
3b. Antibody GMTs (VNA) and GMCs (S-ELISA), 28 days after Vaccination 2.
4a. Solicited local and systemic adverse events (AEs) for 7 days after each vaccination.
4b. Unsolicited AEs for 28 days after each vaccination.
4c. Serious adverse events (SAEs) and adverse events of special interest (AESIs) throughout the study (from first vaccination until end of the study).
Adolescents:
1. Solicited local and systemic AEs for 7 days after vaccination.
2. Unsolicited AEs for 28 days after vaccination.
3. SAEs (incl. Multisystem Inflammatory Syndrome in Children [MIS-C]) and AESIs throughout the study (from first vaccination until end of the study). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
7 or 28 days after each vaccination
Safety endpoints - continuous throughout the study |
|
| E.5.2 | Secondary end point(s) |
Adults:
1a. Serological response to vaccination as measured by VNA titers and ELISA (S-ELISA, EU/mL), 7 days after antigen presentation.
1b. Antibody GMTs (VNA) and GMCs (S-ELISA), 7 days after antigen presentation.
2a. Solicited local and systemic AEs for 7 days after antigen presentation.
2b. Unsolicited AEs for 28 days after antigen presentation.
2c. SAEs and AESIs throughout the study (from antigen presentation until end of the study).
3a. Neutralizing antibody titers to the wild-type SARS-CoV-2 virus expressing S protein as measured by VNA, at all blood collection timepoints.
3b. Binding antibody titers to SARS-CoV-2 or individual SARS-CoV-2 proteins (eg, S protein) as measured by ELISA, at all blood collection timepoints.
Adolescents:
1. Serological response to vaccination as measured by VNA titers and ELISA (SELISA, EU/mL), 28 days after vaccination.
2. Antibody GMTs (VNA) and GMCs (S-ELISA), 28 days after vaccination.
3. Neutralizing antibody titers to the wild-type SARS-CoV-2 virus expressing S protein as measured by VNA, at all blood collection timepoints.
4. Binding antibody titers to SARS-CoV-2 or individual SARS-CoV-2 proteins (eg, S protein) as measured by ELISA, at all blood collection timepoints. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
- 7 or 28 days after antigen presentation
- 28 days after vaccination
- at all blood collection timepoints
|
|
| 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 | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Reactogenicity and Immunogenicity |
|
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | 16 |
| E.8.3 |
Will this trial be conducted at a single site globally?
| No |
| E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
| Netherlands |
| Spain |
| Germany |
| United Kingdom |
|
| 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.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 9 |
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