A Study of Ad26.COV2.S in Adults (COVID-19)

Study Overview
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Brief Summary
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The purpose of the study is to assess the safety, reactogenicity, and immunogenicity of Ad26.COV2.S at 2 dose levels, administered intramuscularly (IM) as a single-dose or 2-dose schedule, with a single booster vaccination administered in one cohort in healthy adults aged greater than or equal to (>=) 18 to less than or equal to (<=) 55 years and in adults aged >= 65 years in good health with or without stable underlying conditions. The purpose of the study is also to assess the safety and reactogenicity of Ad26.COV2.S administered as ad hoc booster vaccination in healthy adults aged >= 18 to <= 55 years and in adults >= 65 years in good health with or without stable underlying conditions.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase 1/2a Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Ad26COVS1 in Adults Aged 18 to 55 Years Inclusive and Adults Aged 65 Years and Older

Conditions
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Covid-19 Prevention

Intervention / Treatment
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* Biological: Ad26.COV2.S
* Biological: Placebo


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 All female participants of childbearing potential must have a negative highly sensitive urine pregnancy test at screening; and have a negative highly sensitive urine pregnancy test immediately prior to each study vaccine administration Participant must have a body mass index (BMI) less than or equal to (<=) 30.0 kilograms per square meter (kg/m^2) Applicable to Cohorts 1 and 2 only: Participant must be healthy, in the investigator's clinical judgment, as confirmed by medical history, physical examination, clinical laboratory assessments, and vital signs performed at screening, and must not have comorbidities related to an increased risk of severe coronavirus disease-2019 (COVID-19). Applicable to Cohort 3 only: In the investigator's clinical judgment, participant must be either in good or stable health Participants may have underlying illnesses such as hyperlipoproteinemia or hypothyroidism, as long as their symptoms and signs are medically controlled and not considered to be comorbidities related to an increased risk of severe COVID-19 (participants may have medical conditions of mild severity (according to the Toxicity Grading Scale), 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, for example, thiazides, Beta blockers, Alpha blockers at the same effective dose). 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 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 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) Participant has a history of any neurological disorders or seizures including Guillain-Barre syndrome, with the exception of febrile seizures during childhood Participant has a positive diagnostic test result for SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) at screening Participants with comorbidities that are or might be associated with an increased risk of progression to severe COVID-19, that is, 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/m^2); chronic liver disease, including cirrhosis; sickle cell disease; thalassemia; cerebrovascular disease; neurologic conditions (dementia); smoking end stage renal disease; organ transplantation; cancer; HIV infection and other immunodeficiencies; hepatitis B infection; and sleep apnea. Applicable to Cohort 3 only: Participants may have hypertension of mild severity (according to the Toxicity Grading Scale), 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, for example, thiazides, Beta blockers, Alpha blockers at the same effective dose) Applicable to Cohorts 1 and 3 only: Participant currently working in an occupation with a high risk of exposure to SARS-CoV-2 (for example, health care worker or emergency response personnel) or considered at the investigator's discretion to be at increased risk to acquire COVID-19 for any other reason

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1a<br>Participants (healthy adults aged greater than or equal to (>=)18 to less than or equal to (<=) 55 years) will receive Ad26.COV2.S at 2 dose levels, as a single dose or 2 dose schedule with an 8-week interval or matching Placebo on Day 1 and Day 57. At unblinding visit, post Emergency Use Authorization (EUA), conditional licensure, or approval for the single dose regimen of Ad26.COV2.S vaccine, participants initially receiving placebo will be offered to receive a single dose of Ad26.COV2.S. If they choose not to receive Ad26.COV2.S they will be asked to continue to be followed in this study. All eligible participants who have previously received coronavirus disease-2019 (COVID-19) vaccination (as primary regimen or additional dose) if the last vaccination was >=6 months ago, will be offered to receive a single ad hoc booster dose of Ad26.COV2.S. If they choose not to receive ad-hoc booster dose they will be asked to continue to be followed in this study. | Biological: Ad26.COV2.S<br>* Participants will receive intramuscular (IM) injection of Ad26.COV2.S.<br>* Other names: Ad26COVS1;Biological: Placebo<br>* Participants will receive Placebo.<br>|
| Experimental: Cohort 1b<br>Participants (healthy adults aged >=18 to <= 55 years) will receive Ad26.COV2.S as a single vaccination in the primary regimen or matching Placebo on Day 1 and Day 57. At unblinding visit, post EUA, conditional licensure, or approval for the single dose regimen of Ad26.COV2.S vaccine, participants initially receiving placebo will be offered to receive a single dose of Ad26.COV2.S. If they choose not to receive Ad26.COV2.S they will be asked to continue to be followed in this study. All eligible participants who have previously received any COVID-19 vaccination (as primary regimen or additional dose) if the last vaccination was >=6 months ago will be offered to receive a single ad hoc booster dose of Ad26.COV2.S. If they choose not to receive ad-hoc booster dose they will be asked to continue to be followed in this study. | Biological: Ad26.COV2.S<br>* Participants will receive intramuscular (IM) injection of Ad26.COV2.S.<br>* Other names: Ad26COVS1;Biological: Placebo<br>* Participants will receive Placebo.<br>|
| Experimental: Cohort 2a<br>Participants (healthy adults aged >=18 to <=55 years) will receive Ad26.COV2.S as single vaccination in the primary regimen or matching Placebo on Day 1, followed by booster vaccination at 6 or 12 months with same dose or matching Placebo. At unblinding visit, post EUA, conditional licensure, or approval for the single dose regimen of Ad26.COV2.S vaccine, participants initially receiving placebo will be offered to receive a single dose of Ad26.COV2.S vaccine and who are not willing to receive single dose of Ad26.COV2.S vaccine will continue to receive booster vaccination. All eligible participants who have previously received any COVID-19 vaccination (as primary regimen or additional dose) if the last vaccination was >= 6 months ago, will be offered to receive a single ad hoc booster dose of Ad26.COV2.S and who are not willing to receive single ad hoc booster dose of Ad26.COV2.S or are not eligible to receive the ad hoc booster dose will continue to receive booster vaccination. | Biological: Ad26.COV2.S<br>* Participants will receive intramuscular (IM) injection of Ad26.COV2.S.<br>* Other names: Ad26COVS1;Biological: Placebo<br>* Participants will receive Placebo.<br>|
| Experimental: Cohort 2b<br>Participants(healthy adults aged >=18 to <=55 years)will receive Ad26.COV2.S in primary regimen or matching Placebo on Day 1 and 57,followed by booster vaccination at 8 or 14 months (that is, 6 or 12 months after completion of primary regimen)with same dose or matching Placebo.At unblinding visit,post EUA,conditional licensure,or approval for single dose regimen of Ad26.COV2.S vaccine,participants initially receiving placebo will be offered to receive single dose of Ad26.COV2.S vaccine and who are not willing to receive single dose of Ad26.COV2.S vaccine will continue to receive booster vaccination.All eligible participants who have previously received any COVID-19 vaccination(as primary regimen or additional dose)if last vaccination was >= 6 months ago,will be offered to receive single ad hoc booster dose of Ad26.COV2.S and who are not willing to receive single ad hoc booster dose of Ad26.COV2.S or are not eligible for ad hoc booster dose will continue to receive booster vaccination. | Biological: Ad26.COV2.S<br>* Participants will receive intramuscular (IM) injection of Ad26.COV2.S.<br>* Other names: Ad26COVS1;Biological: Placebo<br>* Participants will receive Placebo.<br>|
| Experimental: Cohort 3<br>Participants (good or stable health adults aged >=65 years) will receive Ad26.COV2.S at 2 dose levels, as a single dose or 2 dose schedule with an 8-week interval or matching Placebo on Day 1 and Day 57. At unblinding visit, post EUA, conditional licensure, or approval for the single dose regimen of Ad26.COV2.S vaccine, participants initially receiving placebo will be offered to receive a single dose of Ad26.COV2.S. If they choose not to receive Ad26.COV2.S they will be asked to continue to be followed in this study. All eligible participants who have previously received any COVID-19 vaccination (as primary regimen or additional dose) if the last vaccination was >=6 months ago will be offered to receive a single ad hoc booster dose of Ad26.COV2.S. If they choose not to receive ad-hoc booster dose or if they are not eligible for ad-hoc booster dose, then they will be asked to continue to be followed in this study. | Biological: Ad26.COV2.S<br>* Participants will receive intramuscular (IM) injection of Ad26.COV2.S.<br>* Other names: Ad26COVS1;Biological: Placebo<br>* Participants will receive Placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohorts 1, 2, and 3: Number of Participants with Solicited Local Adverse Events (AEs) for 7 Days after First Vaccination | Solicited local AEs are pre-defined local (at the injection site) adverse events for which participants are specifically questioned and which are noted by participants in their diary for 7 days after first vaccination. Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. | Day 8 (7 Days after first vaccination on Day 1) | 
| Cohorts 1, 2, and 3: Number of Participants with Solicited Local Adverse Events (AEs) for 7 Days after Second Vaccination | Solicited local AEs are pre-defined local (at the injection site) adverse events for which participants are specifically questioned and which are noted by participants in their diary for 7 days after second vaccination. Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. | Day 64 (7 Days after second vaccination on Day 57) | 
| Cohorts 1, 2, and 3: Number of Participants with Solicited Systemic AEs for 7 Days after First Vaccination | Participants will be instructed on how to record daily temperature using a thermometer and also instructed to note signs and symptoms in the diary on a daily basis for 7 days after first vaccination. Solicited systemic AEs are fatigue, headache, nausea, and myalgia. | Day 8 (7 Days after first vaccination on Day 1) | 
| Cohorts 1, 2, and 3: Number of Participants with Solicited Systemic AEs for 7 Days after Second Vaccination | Participants will be instructed on how to record daily temperature using a thermometer and also instructed to note signs and symptoms in the diary on a daily basis for 7 days after second vaccination. Solicited systemic AEs are fatigue, headache, nausea, and myalgia. | Day 64 (7 Days after second vaccination on Day 57) | 
| Cohorts 1, 2, and 3: Number of Participants with Unsolicited AEs for 28 Days after First Vaccination | Number of participants with unsolicited AEs for 28 days after first vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned. | Day 29 (28 Days after first vaccination on Day1) | 
| Cohorts 1, 2, and 3: Number of Participants with Unsolicited AEs for 28 Days after Second Vaccination | Number of participants with unsolicited AEs for 28 days after second vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned. | Day 85 (28 Days after second vaccination) | 
| Cohorts 1 and 3: Number of Participants with Serious Adverse Events (SAEs) from the First Vaccination until 2 Years after the Second Vaccination | SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. | Day 1 (vaccination 1) up to 2 years after second vaccination (up to Day 787) | 
| Cohort 2: Number of Participants with SAEs from the First Vaccination until 6 Months after the First Vaccination | SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. | Day 1 (vaccination 1) up to 6 Months | 
| Cohort 2: Number of Participants with SAEs from the First Vaccination until 6 Months after the Second Vaccination | SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. | Day 1 (vaccination 1) up to 6 months after second vaccination (Day 239) | 
| Cohorts 1 and 3: Number of Participants with Adverse Events of Special Interest (AESIs) from the First Vaccination until 2 Years after the Second Vaccination | Number of participants with AESIs will be reported. Thrombosis with thrombocytopenia syndrome is considered to be an AESI. | Day 1 (vaccination 1) up to 2 year after second vaccination (up to Day 787) | 
| Cohort 2: Number of Participants with AESIs from the First Vaccination until 6 Months after the First Vaccination | Number of participants with AESIs will be reported. Thrombosis with thrombocytopenia syndrome is considered to be an AESI. | Day 1 (vaccination 1) up to 6 Months | 
| Cohort 2: Number of Participants with AESIs from the First Vaccination until 6 Months after the Second Vaccination | Number of participants with AESIs will be reported. Thrombosis with thrombocytopenia syndrome is considered to be an AESI. | Day 1 (vaccination 1) up to 6 months after second vaccination (Day 239) | 
| Number of Participants with Solicited Local AEs for 7 Days after ad hoc Booster Vaccination | Solicited local AEs are pre-defined local (at the injection site) adverse events for which participants are specifically questioned and which are noted by participants in their diary for 7 days after ad hoc vaccination. Solicited local AEs are injection site pain/tenderness, erythema, and swelling at the vaccination site. | Up to 7 days after ad hoc booster vaccination | 
| Number of Participants with Solicited Systemic AEs for 7 Days after ad hoc Booster Vaccination | Participants will be instructed on how to record daily temperature using a thermometer and also instructed to note signs and symptoms in the diary on a daily basis for 7 days after ad hoc booster vaccination. Solicited systemic AEs are fatigue, headache, nausea, and myalgia. | Up to 7 days after ad hoc booster vaccination | 
| Number of Participants with Unsolicited AEs for 28 Days after ad hoc Booster Vaccination | Number of participants with unsolicited AEs for 28 days after ad hoc booster vaccination will be reported. Unsolicited AEs are all AEs for which the participant is not specifically questioned. | Up to 28 days after ad hoc booster vaccination | 
| Number of Participants with SAEs from ad hoc Booster Vaccination Until the end of the Study | SAE is an adverse event resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. | from ad hoc booster vaccination (greater or equal to [>=] 6 months after last Covid-19 vaccination [within 120 days]) to end of study (up to 38 months) | 
| Number of Participants with AESIs from ad hoc Booster Vaccination Until the end of the Study | Number of participants with AESIs will be reported. Thrombosis with thrombocytopenia syndrome is considered to be an AESI. | from ad hoc booster vaccination (>= 6 months after last Covid-19 vaccination [within 120 days]) to end of study (up to 38 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohorts 1, 2, and 3: Number of Participants With SARS-CoV-2 Neutralizing Antibody Titers as Assessed by Virus Neutralization Assay (VNA) | Number of participants with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) neutralizing antibody titers as assessed by VNA to measure the humoral immune responses will be reported. | Up to 38 Months | 
| Cohorts 1, 2, and 3: Number of Participants with SARS-CoV-2 Binding Antibodies Assessed by ELISA | Number of participants with SARS-CoV-2 binding antibodies as assessed by enzyme-linked immunosorbent assay (ELISA) to measure humoral immune response will be reported. | Up to 38 Months | 
| Cohorts 1, 2, and 3: Number of Participants with T-helper (Th)-1 and Th-2 Immune Responses as Assessed by Flow Cytometry | Number of participants with Th-1 and Th-2 immune responses will be reported. Th1 and Th2 immune responses will be assessed by flow cytometry after SARS-CoV-2 S protein peptide stimulation of peripheral blood mononuclear cells (PBMCs) and intracellular staining [ICS] including cluster of differentiation (CD)-4+/CD-8+, Interferons (INF)-gamma, interleukin [IL] 2, Tumor Necrosis Factor (TNF)-alpha, IL-4, IL-5, IL-13, and/or other Th-1/Th-2 markers. | Up to 38 Months | 
| Platelet Count in Participants on the day of ad hoc Booster Vaccination and 28 days After ad hoc Booster Vaccination | Platelet count in participants on the day of ad hoc booster vaccination and 28 days after ad hoc booster vaccination will be reported. | On the day of ad hoc booster vaccination and up to 28 days after ad hoc booster vaccination | 
| Number of Participants with Normal or Abnormal Results Based on Additional Analysis on Collected Sera Samples in Case of Potential Thromboembolic Events | Number of participants with normal or abnormal results based on additional analysis (including, but not limited to Activated partial thromboplastin time, Prothrombin time, International normalized ratio, Fibrinogen, D-dimer, Lupus anticoagulant, Anti-cardiolipin antibody, Beta-2 glycoprotein, Heparin Induced Thrombocytopenia (HIT)/PF4 antibody Immunoglobulin G (Ab,IgG)(HIT assay), Platelet activation assay (if HIT/PF4 is positive), Homocysteine, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13 Activity and Inhibitor Profile) on collected sera samples in case of reported potential thromboembolic events. | On the day of ad hoc booster vaccination and up to 28 days after ad hoc booster vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS CoV 2, Vaccine, COVID-19, Ad26COVS1, Ad26.COV2.S