A Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-Mediated COVID-19 in Adult Participants

Phase 3

Completed

Conditions: Participants With or Without Stable Co-morbidities Associated With Progression to Severe COVID-19 at Different Stages of the Protocol

Interventions: Biological: Ad26.COV2.S
Other: Placebo

Registration Number: NCT04505722

Lead Sponsor: Janssen Vaccines & Prevention B.V.

Brief Summary: The study will evaluate the efficacy of Ad26.COV2.S in the prevention of molecularly confirmed moderate to severe/critical COVID-19, as compared to placebo, in adult participants.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 44325

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). Note: Participants with visual impairment are eligible for study participation and may have caregiver assistance in completing the electronic clinical outcome assessment (eCOA) questionnaires

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 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 (including investigational drugs for prophylaxis of COVID-19) within 30 days 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 (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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Ad26.COV2.S	Participants will receive IM injection of placebo on Day 1. At Month 6/unblinding visit, post Emergency Use Authorization (EUA), conditional licensure, or approval for the single dose regimen, participants initially receiving placebo will be offered to receive a single dose of Ad26.COV2.S vaccine IM at a dose level of 5\10\^10 vp. At Year 1 (booster visit), participants who previously received any COVID-19 vaccination (as primary regimen or additional dose) will be offered a single booster dose of Ad26.COV2.S at the 5\10\^10 vp dose level.
Ad26.COV2.S	Ad26.COV2.S	Participants will receive intramuscular (IM) injection of Ad26.COV2.S at a dose level of 5\10\^10 virus particles (vp) as single dose vaccine on Day 1. At Year 1 (booster visit), participants who previously received any coronavirus disease-2019 (COVID-19) vaccination (as primary regimen or additional dose) will be offered a single booster dose of Ad26.COV2.S at the 5\10\^10 vp dose level.
Placebo	Placebo	Participants will receive IM injection of placebo on Day 1. At Month 6/unblinding visit, post Emergency Use Authorization (EUA), conditional licensure, or approval for the single dose regimen, participants initially receiving placebo will be offered to receive a single dose of Ad26.COV2.S vaccine IM at a dose level of 5\10\^10 vp. At Year 1 (booster visit), participants who previously received any COVID-19 vaccination (as primary regimen or additional dose) will be offered a single booster dose of Ad26.COV2.S at the 5\10\^10 vp dose level.

Primary Outcome Measures

Name	Time	Method
Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical Coronavirus Disease (COVID-19) With Seronegative Status With Onset at Least 14 Days After Double-blind Vaccination on Day 1 (Day 15): Double-blind Phase	From 14 days after double-blind vaccination on Day 1 (Day 15) up to Month 6	Molecularly confirmed moderate to severe/critical COVID-19 was defined as a severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive reverse transcription/polymerase chain reaction (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. Moderate included one sign or symptom such as respiratory rate \>= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms such as heart rate \>= 90 beats per minute (beats/minute) and symptoms such as cough from a list of signs and symptoms and severe/critical included one of the following signs and symptoms: respiratory rate \>=30 breaths/minute, heart rate \>=125 beats/minute, oxygen saturation (SpO2) \<= 93% on room air at sea level respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to the ICU, death defined as per FDA guidance.
Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 With Seronegative Status With Onset at Least 28 Days After Double-blind Vaccination on Day 1 (Day 29): Double-blind Phase	From 28 days after double-blind vaccination on Day 1 (Day 29) up to Month 6	Molecularly confirmed moderate to severe/critical COVID-19 was 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. Moderate included one sign or symptom such as respiratory rate \>=20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms such as heart rate \>= 90 beats/minute and symptoms such as cough from a list of signs and symptoms and severe/critical included one of the following signs and symptoms: respiratory rate \>=30 breaths/minute, heart rate \>=125 beats/minute, SpO2 less than or equal to (\<=) 93 percent (%) on room air at sea level respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to the Intensive Care Unit (ICU), death defined as per Food and Drug Administration (FDA) guidance.
Number of Participants With Unsolicited AEs Up to 28 Days After Booster Vaccination (Open-label Booster Vaccination Phase)	Up to Day 393 (28 Days after booster vaccination on Day 365 [Year 1])	Unsolicited AEs were all AEs for which the participant is not specifically questioned in the participant diary.
Number of Participants With Solicited Local Adverse Events (AEs) Up to 7 Days After Booster Vaccination (Open-label Booster Vaccination Phase)	Up to Day 372 (7 Days after booster vaccination on Day 365 [Year 1])	Participants who received the booster dose were 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-booster vaccination (day of vaccination and the subsequent 7 days).
Number of Participants With Solicited Systemic AEs Up to 7 Days After Booster Vaccination (Open-label Booster Vaccination Phase)	Up to Day 372 (7 Days after booster vaccination on Day 365 [Year 1])	Participants recorded the temperature in the e-Diary in the evening of the day of vaccination, and then daily for the next 7 days approximately at the same time each day. If more than 1 measurement was made on any given day, the highest temperature of that day was recorded in the e-Diary. Fever was defined as endogenous elevation of body temperature \>= 38.0 degree Celsius or \>=100.4-degree Fahrenheit, as recorded in at least 1 measurement. Participants also noted the signs and symptoms in the e-Diary on a daily basis for 7 days post-booster vaccination (day of vaccination and the subsequent 7 days), if feasible, for the following events: fatigue, headache, nausea, myalgia.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Asymptomatic Infection Detected by RT-PCR at the Time of the Month 6/Unblinding Visit (Double Blind Phase)	Month 6	Number of participants with asymptomatic infection detected by RT-PCR at the time of the Month 6/unblinding visit were reported.
Number of Participants With First Occurrence of Molecularly Confirmed Severe/Critical COVID-19 With Seronegative Status With Onset at Least 28 Days After Double-blind Vaccination on Day 1 (Day 29): Double-blind Phase	From 28 days after double-blind vaccination on Day 1 (Day 29) up to Month 6	Severe/critical COVID-19 was 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 and one of the following signs and symptoms: respiratory rate \>=30 breaths/minute, heart rate \>=125 beats/minute,SpO2 \<=93% on room air at sea level respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to the ICU, death defined as per FDA guidance.
Area Under the Curve (AUC) of 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 (Double Blind Phase)	From Day 15 to end of the COVID-19 episode (Day 189)	AUC of SARS-CoV-2 Viral Load was assessed in confirmed COVID-19 cases using RT-PCR. Nasal swabs were used to detect and/or quantify SARS-CoV-2.
Number of Participants With First Occurrence of Molecularly Confirmed Severe/Critical COVID-19 With Seronegative Status With Onset at Least 14 Days After Double-blind Vaccination on Day 1 (Day 15): Double-blind Phase	From 14 days after double-blind vaccination on Day 1 (Day 15) up to Month 6	Molecularly confirmed severe/critical COVID-19 was 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 and one of the following signs and symptoms: respiratory rate \>=30 breaths/minute, heart rate \>=125 beats/minute,SpO2 \<=93% on room air at sea level respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to the ICU, death defined as per FDA guidance. Seronegative is defined as N-serology seronegative at the time of boosting or at the Year 1 visit if not boosted.
Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of Their Serostatus (Double Blind Phase)	28 days after double-blind vaccination on Day 1 (Day 29)	Molecularly confirmed moderate to severe/critical COVID-19 was 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. Moderate included one sign or symptom such as respiratory rate \>= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms such as heart rate \>= 90 beats per minute (beats/minute) and symptoms such as cough from a list of signs and symptoms and severe/critical included one of the following signs and symptoms: respiratory rate \>=30 breaths/minute, heart rate \>=125 beats/minute,SpO2 \<=93% on room air at sea level respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to the ICU, death defined as per FDA guidance.
Number of Participants With BOD Based on First Occurrence of Molecularly Confirmed Symptomatic COVID-19 (Double Blind Phase)	28 Days after double-blind vaccination on Day 1 (Day 29)	BOD is a weighted version of the mild, moderate, and severe/critical vaccine efficacies and was evaluated based on the first occurrence of molecularly confirmed COVID-19, including mild, moderate or severe/critical COVID-19 case.
Number of Participants With First Occurrence of Molecularly Confirmed, Moderate to Severe/Critical COVID-19 for Seronegative Participants (Double Blind Phase)	1 day after double-blind vaccination on Day 1 (Day 2)	Molecularly confirmed moderate to severe/critical COVID-19 was 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. Moderate included one sign or symptom such as respiratory rate \>= 20 breaths per minute and symptoms such as shortness of breath or two signs or symptoms such as heart rate \>= 90 beats per minute (beats/minute) and symptoms such as cough from a list of signs and symptoms and severe/critical included one of the following signs and symptoms: respiratory rate \>=30 breaths/minute, heart rate \>=125 beats/minute,SpO2 \<=93% on room air at sea level respiratory failure, evidence of shock, significant acute renal, hepatic, or neurologic dysfunction, admission to the ICU, death defined as per FDA guidance. Seronegative is defined as N-serology seronegative at the time of boosting or at the Year 1 visit if not boosted.
Number of Participants With First Occurrence of COVID-19 Requiring Medical Intervention (Double Blind Phase)	28 Days after double-blind vaccination on Day 1 (Day 29)	Number of participants with first occurrence of COVID-19 requiring medical intervention (such as a composite endpoint of hospitalization, ICU admission, mechanical ventilation, and ECMO, linked to objective measures such as decreased oxygenation, X-ray or CT findings) or linked to any molecularly confirmed, COVID-19 at least 28 days post vaccination were reported.
Number of Participants With First Occurrence of Molecularly Confirmed Mild COVID-19 (Double Blind Phase)	28 Days after double-blind vaccination on Day 1 (Day 29)	Molecularly confirmed mild Covid-19 was 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 and one of the following signs and symptoms: fever (\>=38°C or \>=100.4°F), sore throat, malaise (loss of appetite, generally unwell, fatigue, physical weakness), headache, muscle pain (myalgia), gastrointestinal symptoms, cough, chest congestion, runny nose, wheezing, skin rash, eye irritation or discharge, chills, new or changing olfactory or taste disorders, red or bruised looking feet or toes, or shaking chills or rigors.
Number of Participants With Burden of Disease (BOD) Based on First Occurrence of Molecularly Confirmed Symptomatic COVID-19 (Double Blind Phase)	14 Days after double-blind vaccination on Day 1 (Day 15)	BOD is a weighted version of the mild, moderate, and severe/critical vaccine efficacies and was evaluated based on the first occurrence of molecularly confirmed COVID-19, including mild, moderate or severe/critical COVID-19 case.
Number of Participants With SARS-CoV-2 Seroconversion Based on Antibodies to N Protein Using ELISA and/or SARS-CoV-2 Immunoglobulin Assay (Double Blind Phase)	From Day 29 until end of double-blind phase at Month 6	Number of participants with SARS-CoV-2 seroconversion based on antibodies to nucleocapsid (N) protein using enzyme-linked immunosorbent assay (ELISA) and/or SARS-CoV- 2 immunoglobulin assay that is dependent on the SARS-CoV-2 N protein was reported.
Number of Participants With First Occurrence of SARS-CoV-2 Infection (Serologically and/or Molecularly Confirmed) (Double Blind Phase)	28 days after double-blind vaccination on Day 1 (Day 29)	Number of participants with first occurrence of SARS-CoV-2 infection (serologically and/or molecularly confirmed) were reported.
Number of Participants With First Occurrence of Molecularly Confirmed Mild COVID-19 (Double Blind Phase	14 Days after double-blind vaccination on Day1 (Day 15)	Molecularly confirmed mild Covid-19 was 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 and one of the following signs and symptoms: fever (\>=38°C or \>=100.4°F), sore throat, malaise (loss of appetite, generally unwell, fatigue, physical weakness), headache, muscle pain (myalgia), gastrointestinal symptoms, cough, chest congestion, runny nose, wheezing, skin rash, eye irritation or discharge, chills, new or changing olfactory or taste disorders, red or bruised looking feet or toes, or shaking chills or rigors.
Number of Participants With Adverse Events of Special Interest (AESI) (Double Blind Phase)	Baseline (Day 1) up to 35 weeks	Number of participants with AESIs were reported. 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. Thrombosis with Thrombocytopenia Syndrome (TTS), a syndrome characterized by a combination of both a thrombotic event and thrombocytopenia, is considered to be an AESI in this study. A suspected TTS case is defined as: Thrombotic events: suspected deep vessel venous or arterial thrombotic events; Thrombocytopenia, defined as platelet count below 150,000/micro liter.
Number of Participants With First Occurrence of Molecularly Confirmed COVID-19 Defined by the US Food and Drug Administration (FDA) Harmonized Case Definition (Double Blind Phase)	28 Days after double-blind vaccination on Day 1 (Day 29)	Molecularly confirmed COVID-19 was 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 the study 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.
Number of Participants With MAAEs Leading to Study Discontinuation (Double Blind Phase)	Up to 35 weeks	MAAEs were 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 were not considered medically-attended visits. New onset of chronic diseases was collected as part of the MAAEs.
Number of Participants With Solicited Local Adverse Events (AEs) During 7 Days Following Vaccination (Double Blind Phase)	Up to Day 8 (7 Days after double-blind vaccination on Day 1)	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Participants who were enrolled in safety subset were 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-vaccination (day of vaccination and the subsequent 7 days).
Number of Participants With Solicited Systemic AEs During 7 Days Following Vaccination (Double Blind Phase)	Up to Day 8 (7 Days after double-blind vaccination on Day 1)	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with pharmaceutical/biological agent under study. Participants who were enrolled in safety subset were instructed on how to record daily temperature using a thermometer provided for home use. Participants recorded the temperature in the e-Diary in the evening of the day of vaccination, and then daily for the next 7 days approximately at the same time each day. If more than 1 measurement was made on any given day, the highest temperature of that day was recorded in the e-Diary. Fever was defined as endogenous elevation of body temperature \>= 38.0 degree Celsius or \>=100.4-degree Fahrenheit, as recorded in at least 1 measurement. Participants also noted the signs and symptoms in the e-Diary on a daily basis for 7 days post vaccination (day of vaccination and the subsequent 7 days), for the following events: fatigue, headache, nausea, myalgia.
Number of Participants With Binding Antibodies to SARS- CoV-2S Protein as Measured by ELISA (Booster Phase)	29 days after booster vaccination on Day 365 (Day 394)	Number of participants with binding antibodies to SARS- CoV-2S protein as measured by ELISA was reported.
Number of Participants With Serious Adverse Events (SAEs) (Double Blind Phase)	Baseline (Day 1) up to 35 weeks	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. 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.
Number of Participants With Medically-Attended Adverse Events (MAAEs) (Double Blind Phase)	Up to 6 months after double-blind vaccination on Day 1 (up to 6 months)	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. MAAEs were 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.
Number of Participants With Unsolicited AEs During 28 Days Post-vaccination (Double Blind Phase)	Up to Day 29 (28 Days after double-blind vaccination on Day 1)	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Unsolicited AEs were all AEs for which the participant is not specifically questioned in the participant diary.
Binding Antibodies to SARS-CoV-2 S Protein Assessed by ELISA (Double Blind Phase)	Baseline (Day 1), Day 29, and Day 71	Binding antibodies to SARS-CoV-2 S protein as assessed by enzyme-linked immunosorbent assay (ELISA) to measure humoral immune response was reported. The lower limit of quantification (LLOQ) and upper limit of quantification (ULOQ) were 50.3 EU/mL and 58,158.10 EU/mL, respectively. A sample was considered positive if the value was strictly greater than the LLOQ (\>LLOQ).
Number of Participants With Antibody Titers to Ad26.COV2.S (Booster Phase)	28 days after booster vaccination on Day 365 (up to Day 393)	Number of participants with antibody titers to Ad26.COV2.S to measure immune response were reported.

Trial Locations

Locations (205): Synexus Clinical Research US Inc
🇺🇸
Murray, Utah, United States
University of Alabama Birmingham
🇺🇸
Birmingham, Alabama, United States
Alabama Vaccine Research Clinic at UAB
🇺🇸
Birmingham, Alabama, United States
Optimal Research
🇺🇸
Rockville, Maryland, United States
VA Medical Center
🇺🇸
Columbia, South Carolina, United States
Central Phoenix Medical Clinic
🇺🇸
Phoenix, Arizona, United States
Quality of Life Medical & Research Center, LLC
🇺🇸
Tucson, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Central Arkansas Veterans Healthcare System
🇺🇸
Little Rock, Arkansas, United States
Anaheim Clinical Trials, LLC
🇺🇸
Anaheim, California, United States
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Synexus Clinical Research US Inc
🇺🇸Murray, Utah, United States