A Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults

Study Overview
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Brief Summary
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The study will evaluate the efficacy of Ad26.COV2.S in the prevention of molecularly confirmed moderate to severe/critical coronavirus disease-2019 (COVID-19), as compared to placebo, in SARS-CoV-2 seronegative adults in the double-blind phase and to describe COVID-19 outcomes, safety, and immunogenicity in the different study cohorts in open-label phase.

Detailed Description
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The aim of the COVID-19 vaccine clinical development program is to develop a safe and effective vaccine for the prevention of COVID-19. Ad26.COV2.S, a COVID-19 vaccine based on a human replication-incompetent Ad26 vector, constructed to encode the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus spike (S) protein, is being developed. The study will consist of: a screening phase (up to 28 days), study period (60-week), and a long-term follow-up period (1 additional year). The total study duration will be maximum 2 years and 3 months for the participants. Assessments for efficacy (COVID-19 signs and symptoms, etc.), immunogenicity (such as humoral immune responses), and safety (such as adverse events [AEs] monitoring) will be performed throughout the study.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase 3 Study to Assess the Efficacy and Safety of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults Aged 18 Years and Older

Conditions
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Participants With or Without Stable Co-morbidities Associated With Progression to Severe COVID-19

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Contraceptive (birth control) use should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies All 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 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 Must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study Must be able to read, understand, and complete questionnaires in the electronic clinical outcome assessment (eCOA) (that is, the coronavirus disease-2019 [COVID 19] signs and symptoms surveillance question, the e-Diary, and the electronic patient-reported outcomes (ePROs) 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 (100.4-degree Fahrenheit) 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 Participant received or plans to receive: (a) licensed live attenuated vaccines - within 28 days before or after planned administration of study vaccine; and (b) other licensed (not live) vaccines - within 14 days before or after planned administration of study vaccine Participant previously received a coronavirus vaccine Participant received an investigational drug within 30 days (including investigational drugs for prophylaxis of COVID-19) or used an invasive investigational medical device within 30 days or received investigational immunoglobulin (Ig) or investigational monoclonal antibodies within 3 months, or received convalescent serum for COVID-19 treatment within 4 months or received an investigational vaccine (including investigational Adenoviral-vectored vaccines) 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ad26.COV2.S<br>Participants will receive intramuscular (IM) injection of Ad26.COV2.S vaccine on Day 1 and Day 57 in the double-blind phase. At unblinding visit (open-label phase), participants who have not yet received second vaccination will receive second dose of Ad26.COV2.S vaccine on Day 57, if applicable and newly enrolled participants will either receive IM injection of one dose of Ad26.COV2.S vaccine on Day 1 or two doses of Ad26.COV2.S vaccine on Day 1 and Day 57. All ongoing participants who only received a single vaccination with Ad26.COV2.S in the study will be offered to receive single booster dose of Ad26.COV2.S in the open label phase preferably within 6 to 12 months after the participant's first Ad26.COV2.S vaccination. | Biological: Ad26.COV2.S<br>* Ad26.COV2.S vaccine will be administered on Day 1 and Day 57 in the double-blind phase. At unblinding visit Ad26.COV2.S vaccine will be administered to participants at Day 57 who have not yet received second vaccination and in newly enrolled participants as either single dose on Day 1 or two doses on Day 1 and Day 57. Single dose of Ad26.COV2.S vaccine will also be administered to participants initially receiving placebo. Single booster dose of Ad26.COV2.S vaccine will be given to participants in the open label phase who have received only a single vaccination with Ad26.COV2.S.<br>* Other names: VAC31518;|
| Placebo Comparator: Placebo<br>Participants will receive IM injection of placebo on Day 1 and Day 57 in the double-blind phase. At unblinding visit (open-label phase), participants initially receiving placebo will be offered to receive IM injection of a single dose of Ad26.COV2.S vaccine. All ongoing participants who only received a single vaccination with Ad26.COV2.S in the study will be offered to receive single booster dose of Ad26.COV2.S in the open label phase preferably within 6 to 12 months after the participant's first Ad26.COV2.S vaccination. | Biological: Ad26.COV2.S<br>* Ad26.COV2.S vaccine will be administered on Day 1 and Day 57 in the double-blind phase. At unblinding visit Ad26.COV2.S vaccine will be administered to participants at Day 57 who have not yet received second vaccination and in newly enrolled participants as either single dose on Day 1 or two doses on Day 1 and Day 57. Single dose of Ad26.COV2.S vaccine will also be administered to participants initially receiving placebo. Single booster dose of Ad26.COV2.S vaccine will be given to participants in the open label phase who have received only a single vaccination with Ad26.COV2.S.<br>* Other names: VAC31518;Other: Placebo<br>* Placebo will be administered as IM injection on Day 1 and Day 57.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Double Blind Phase and Open-label Phase: Number of Participants with Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 | Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate greater than or equal to (>=) 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of signs and symptoms or severe COVID-19 defined in Food and Drug Administration (FDA) guidance. | At least 14 days after the second vaccination (Day 71) to the end of study (2 years and 3 months [after last participant enrolled]) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Double Blind Phase: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of their Serostatus | Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance. | 1 day after the 1st vaccination (Day 2) to end of study (2 years and 3 months) | 
| Double Blind Phase: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of their Serostatus | Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance. | 14 days after the second vaccination (Day 71) to end of study (2 years and 3 months) | 
| Double Blind Phase: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 and who were Seronegative at Baseline | Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance. | 1 day after the 1st vaccination (Day 2) to end of study (2 years and 3 months) | 
| Double Blind Phase: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 and who were Seronegative at Baseline | Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance. | 14 days after the 1st vaccination (Day 15) to end of study (2 years and 3 months) | 
| Double Blind Phase: Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 and who were Seronegative at Baseline | Moderate defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms from a list of sign and symptoms or severe COVID-19 defined in FDA guidance. | 28 days after the 1st vaccination (Day 29) to end of study (2 years and 3 months) | 
| Double Blind Phase: Number of Participants with First Occurrence of COVID-19 Requiring Medical Intervention | Number of participants with first occurrence of COVID-19 requiring medical intervention (such as a composite endpoint of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and extracorporeal membrane oxygenation (ECMO), linked to objective measures such as decreased oxygenation, X-ray, computed tomographic [CT] findings) and linked to any molecularly confirmed COVID-19 at least 14 days after the second vaccination will be reported. | At least 14 days after the second vaccination (Day 71) to end of study (2 years and 3 months) | 
| Double Blind Phase: SARS-CoV-2 Viral Load as Assessed by Quantitative Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) in Participants with Molecularly Confirmed, Moderate to Severe/Critical COVID-19 | The viral load of Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) will be assessed in confirmed COVID-19 cases using RT-PCR. Nasal swabs will be used to detect and/or quantify SARS-CoV-2. | At least 14 days after the second vaccination (Day 71) to end of study (2 years and 3 months) | 
| Double Blind Phase: Number of Participants with First Occurrence of Molecularly Confirmed Mild COVID-19 | Molecularly confirmed mild COVID-19 is defined as a SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample. Mild COVID-19 includes: Fever, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, cough, chest congestion, runny nose, wheezing, skin rash, eye irritation or discharge, or chills, without shortness of breath or dyspnea. | At least 14 days after the second vaccination (Day 71) to end of study (2 years and 3 months) | 
| Double Blind Phase: Number of Participants with First Occurrence of Molecularly confirmed COVID-19 Defined by the US FDA Harmonized Case Definition | Molecularly confirmed moderate and severe/critical COVID-19 defined as a positive SARS-CoV-2 positive RT-PCR or molecular test result from any available respiratory tract sample (example, nasal swab sample, sputum sample, throat swab sample, saliva sample) or other sample; and COVID-19 symptoms consistent with those defined by the US FDA harmonized case definition at the time of finalization of this protocol: fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, diarrhea. | At least 14 days after the second vaccination (Day 71) to end of study (2 years and 3 months) | 
| Double Blind Phase: Burden of Disease (BOD) Based on First Occurrence of Molecularly Confirmed Symptomatic COVID-19 | BOD will be evaluated based on the first occurrence of molecularly confirmed COVID-19, including mild, moderate, or severe/critical COVID-19 case. | At least 14 days after the second vaccination (Day 71) to end of study (2 years and 3 months) | 
| Double Blind Phase: Serologic Conversion Between Baseline and Other Blood Samples up to Unblinding Visit Using an Enzyme-linked Immunosorbent Assay (ELISA) | Serologic conversion between baseline and other blood samples up to unblinding visit using an ELISA and/or SARS-CoV- 2 immunoglobulin assay that is dependent on the SARS-CoV-2 nucleocapsid (N) protein will be reported. | Between baseline and unblinding visit (up to 6 months) | 
| Double Blind Phase: Number of Participants With Asymptomatic Infection Detected By Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) | Number of participants with asymptomatic infection as assessed by RT-PCR will be reported. | Up to 2 years and 3 months | 
| Double Blind Phase: Number of Participants with First Occurrence of SARS-CoV-2 Infection (Serologically and/or Molecularly Confirmed) | Number of participants with first occurrence of SARS-CoV-2 infection (serologically and/or molecularly confirmed) with onset at least 14 days after second vaccination (Day 71) to end of Study (2.3 years) will be reported. | At least 14 days after the second vaccination (Day 71) to end of study (2 years and 3 months) | 
| Double Blind Phase and Open-label Phase: Number of Participants with Serious Adverse Events (SAEs) | SAE is any untoward medical occurrence that at any dose may result 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 2 years and 3 months | 
| Double Blind Phase and Open-label Phase: Number of Participants with Adverse Events of Special Interest (AESIs) | AESIs are significant AEs that are judged to be of special interest because of clinical importance, known or suspected class effects, or based on nonclinical signals. | Up to 2 years and 3 months | 
| Double Blind Phase and Open-label Phase: 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 the last vaccination (Up to 34 weeks) | 
| Double Blind Phase and Open-label Phase: Number of Participants with Medically-attended Adverse Events (MAAEs) Leading to Study Discontinuation | 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. | Up to 2 years and 3 months | 
| Double Blind Phase: Number of Participants with Solicited Local Adverse Events (AEs) During 7 Days Following Each Vaccination | Participants will be asked to note in the e-Diary occurrences of injection site pain/tenderness, erythema, and swelling at the study vaccine injection site daily for 7 days post each vaccination (day of each vaccination and the subsequent 7 days). | Up to Day 8 (7 days after first vaccination on Day 1), up to Day 64 (7 days after second vaccination on Day 57) | 
| Double Blind Phase: Number of Participants with Solicited Systemic AEs During 7 Days Following Each Vaccination | Participants will be instructed on how to record daily temperature using a thermometer provided for home use. Participants should record the temperature in the e-Diary in the evening of the day of each vaccination, and then daily for the next 7 days approximately at the same time each day. If more than 1 measurement is made on any given day, the highest temperature of that day will be recorded in the e-Diary. Fever is defined as endogenous elevation of body temperature >= 38.0 degree Celsius or >=100.4-degree Fahrenheit, as recorded in at least 1 measurement. Participants will also be instructed on how to note signs and symptoms in the e-Diary on a daily basis for 7 days post each vaccination (day of each vaccination and the subsequent 7 days), for the following events: fatigue, headache, nausea, myalgia. | Up to Day 8 (7 days after first vaccination on Day 1), up to Day 64 (7 days after second vaccination on Day 57) | 
| Double Blind Phase: Number of Participants with Unsolicited Adverse Events (AEs) During 28 Days Post-vaccination | Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary. | Up to Day 29 (28 days after first vaccination on Day 1), up to Day 85 (28 days after second vaccination on Day 57) | 
| Double Blind Phase: SARS-CoV-2 Binding Antibodies Assessed by ELISA | SARS-CoV-2 binding antibodies as assessed ELISA to measure humoral immune response will be reported. | Up to 2 years and 3 months |