A Study to Evaluate Dose Levels of Ad26.COV2.S Administered as a Two-dose Schedule in Healthy Adults

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate non-inferiority (NI) in terms of humoral immune responses after 6 dose levels of Ad26.COV2.S.

Official Title
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A Randomized, Double-blind, Phase 3 Study to Evaluate 6 Dose Levels of Ad26.COV2.S Administered As a Two-Dose Schedule in Healthy Adults

Conditions
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COVID-19 Prevention

Intervention / Treatment
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* Biological: Ad26.COV2.S


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must sign an informed consent form (ICF) indicating that he or she understands the purpose, procedures and potential risks and benefits of the study, and is willing to participate in the study Participant must be healthy, in the investigator's clinical judgment, as confirmed by medical history, physical examination, and vital signs performed at screening. 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 Coronavirus disease 2019 (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 All female 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 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 Participant must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study Exclusion Criteria: Participant has a clinically significant acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature greater than or equal to (>=) 38.0 degree Celsius (C) (100.4 degree Fahrenheit [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 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) Participant received or plans to receive: (a) licensed live attenuated vaccines - within 28 days before or after planned administration of the first or subsequent study vaccinations; and (b) other licensed (not live) vaccines - within 14 days before or after planned administration of the first or subsequent study vaccinations 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 investigational immunoglobulin (Ig) or monoclonal antibodies within 3 months, or received convalescent serum for COVID-19 treatment within 4 months or received an investigational vaccine within 6 months before the planned administration of the first dose of study vaccine or is currently enrolled or plans to participate in another investigational study during the course of this study Participant previously received a coronavirus vaccine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Ad26.COV2.S Dose Level 1<br>Participants in the main study and sub study will receive intramuscular (IM) injections of Ad26.COV2.S as a 2-dose vaccination regimen at dose level 1 on Days 1 and 57. | Biological: Ad26.COV2.S<br>* Participants will receive intramuscular (IM) injections of Ad26.COV2.S.<br>* Other names: VAC31518;|
| Experimental: Group 2: Ad26.COV2.S Dose Level 2<br>Participants will receive IM injections of Ad26.COV2.S as a 2-dose vaccination regimen at dose level 2 on Days 1 and 57 in the main study. | Biological: Ad26.COV2.S<br>* Participants will receive intramuscular (IM) injections of Ad26.COV2.S.<br>* Other names: VAC31518;|
| Experimental: Group 3: Ad26.COV2.S Dose Level 3<br>Participants in the main study and sub study will receive IM injections of Ad26.COV2.S as a 2-dose vaccination regimen at dose level 3 on Days 1 and 57. | Biological: Ad26.COV2.S<br>* Participants will receive intramuscular (IM) injections of Ad26.COV2.S.<br>* Other names: VAC31518;|
| Experimental: Group 4: Ad26.COV2.S Dose Level 4<br>Participants will receive IM injections of Ad26.COV2.S as a 2-dose vaccination regimen at dose level 4 on Days 1 and 57 in the main study. | Biological: Ad26.COV2.S<br>* Participants will receive intramuscular (IM) injections of Ad26.COV2.S.<br>* Other names: VAC31518;|
| Experimental: Group 5: Ad26.COV2.S Dose Level 5<br>Participants in the main study and sub study will receive IM injections of Ad26.COV2.S as a 2-dose vaccination regimen at dose level 5 on Days 1 and 57. | Biological: Ad26.COV2.S<br>* Participants will receive intramuscular (IM) injections of Ad26.COV2.S.<br>* Other names: VAC31518;|
| Experimental: Group 6: Ad26.COV2.S Dose Level 6<br>Participants in the main study and sub study will receive IM injections of Ad26.COV2.S as a 2-dose vaccination regimen at dose level 6 on Days 1 and 57. | Biological: Ad26.COV2.S<br>* Participants will receive intramuscular (IM) injections of Ad26.COV2.S.<br>* Other names: VAC31518;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Main Study: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) S Protein Binding Antibodies Concentration Measured by Enzyme-Linked Immunosorbent Assay (ELISA) 28 Days After First Vaccination | SARS-CoV-2 S protein binding antibodies concentration measured by ELISA will be reported. | 28 days after first vaccination (Day 29) | 
| Main Study: ELISA Geometric Mean Concentrations (GMCs) 28 Days After First Vaccination | Non-inferiority (NI) will be assessed in terms of humoral immune response expressed by the GMCs of S-ELISA. | 28 days after first vaccination (Day 29) | 
| Main Study: SARS-CoV-2 S Protein Binding Antibodies Concentration Measured by ELISA 14 Days After Second Vaccination | SARS-CoV-2 S protein binding antibodies concentration measured by ELISA will be reported. | 14 days after second vaccination (Day 71) | 
| Main Study: ELISA GMCs 14 Days After Second Vaccination | NI will be assessed in terms of humoral immune response expressed by the GMCs of S-ELISA. | 14 days after second vaccination (Day 71) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Main and Sub Study: Serological Response to Vaccination to SARS-COV-2 S Protein as Measured by ELISA | Serological response to vaccination to SARS-COV-2 S protein as measured by ELISA will be reported. | Up to 60 weeks | 
| Main and Sub Study: SARS-CoV-2 S Protein Binding Antibody GMCs as Measured by ELISA or Equivalent Assay | SARS-CoV-2 S protein binding antibody GMCs as measured by ELISA or equivalent assay will be reported. | Up to 60 weeks | 
| Main and Sub Study: Number of Participants with Solicited Local Adverse Events (AEs) for 7 Days After Each Vaccination | Solicited local AEs include injection site pain/tenderness, erythema and swelling at the study vaccine injection site and the extent (largest diameter) of any erythema and swelling (using the ruler supplied) will be noted in the participant diary after 7 days after each vaccination. | 7 days after first vaccination on Day 1 (up to Day 8); 7 days after second vaccination on Day 57 (up to Day 64) | 
| Main and Sub Study: Number of Participants with Solicited Systemic AEs for 7 Days After Each Vaccination | Solicited systemic AEs (include body temperature, fatigue, headache, nausea, myalgia) will be noted in the participant diary after 7 days of each vaccination. | 7 days after first vaccination on Day 1 (up to Day 8); 7 days after second vaccination on Day 57 (up to Day 64) | 
| Main and Sub Study: Number of Participants with Unsolicited AEs for 28 Days After Each Vaccination | Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary. | 28 days after first vaccination on Day 1 (up to Day 29); 28 days after second vaccination on Day 57 (up to Day 85) | 
| Main and Sub Study: Number of Participants with Serious Adverse Events (SAEs) | SAE is any untoward medical occurrence that at any dose may results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. | Up to 60 weeks | 
| Main and Sub Study: Number of Participants with Adverse Events of Special Interest (AESIs) | Number of participants with AESIs will be reported. Thrombosis with thrombocytopenia syndrome is considered to be an AESI. | Up to 60 weeks | 
| Main and Sub Study: Number of Participants with Medically-Attended Adverse Events (MAAEs) | MAAEs are defined as AEs with medically-attended visits including hospital, emergency room, urgent care clinic, or other visits to or from medical personnel for any reason. Routine study visits will not be considered medically-attended visits. New onset of chronic diseases will be collected as part of the MAAEs. | 6 months after second vaccination (up to 32 weeks) | 
| Main Study: Number of Participants with AEs Leading to Study Discontinuation | Number of participants with AEs leading to study discontinuation will be reported. | Up to 60 weeks |