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

• ClinicalTrials.gov Identifier: NCT04505722
• Recruitment Status: Completed
• First Posted: August 10, 2020
• Results First Posted: April 15, 2022
• Last Update Posted: May 6, 2023
• Sponsor: Janssen Vaccines & Prevention B.V.
• Information provided by (Responsible Party): Janssen Vaccines & Prevention B.V.

Tracking Information

• First Submitted Date: July 31, 2020
• First Posted Date: August 10, 2020
• Results First Submitted Date: January 25, 2022
• Results First Posted Date: April 15, 2022
• Last Update Posted Date: May 6, 2023
• Actual Study Start Date: September 7, 2020
• Actual Primary Completion Date: March 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 25, 2022)

• Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical Coronavirus Disease (COVID-19) With Seronegative Status (Main Study) [ Time Frame: 14 Days after double-blind vaccination (Day 15) ]
  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 (Main Study) [ Time Frame: 28 Days after double-blind vaccination (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/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 Solicited Local Adverse Events (AEs) Up to 7 Days After Booster Vaccination (Open-label Booster Vaccination Phase) [ Time Frame: Up to Day 372 (7 Days after booster vaccination on Day 365 [Year 1]) ]
  Participants who receive the booster dose was 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) [ Time Frame: 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.
• Number of Participants With Unsolicited AEs Up to 28 Days After Booster Vaccination (Open-label Booster Vaccination Phase) [ Time Frame: 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 Serious Adverse Events (SAEs) From Booster Vaccination Until End of the Study (Open-label Booster Vaccination Phase) [ Time Frame: From booster vaccination (Year 1) up to end of the study (up to 2 years 3 months) ]
  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 Adverse Events of Special Interest (AESI) From Booster Vaccination Until End of the Study (Open-label Booster Vaccination Phase) [ Time Frame: From booster vaccination (Year 1) up to end of the study (up to 2 years 3 months) ]
  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 Moderate to Severe/Critical Coronavirus Disease (COVID-19) With Seronegative Status (Open-label Booster Vaccination Phase) [ Time Frame: 14 Days after unblinding visit to 1 year follow up of the last booster vaccination (up to Day 546) ]
  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 First Occurrence of Molecularly Confirmed Moderate to Severe/Critical Coronavirus Disease (COVID-19) With Seronegative Status (Open-label Booster Vaccination Phase) [ Time Frame: 28 Days after unblinding visit to 1 year follow up of the last booster vaccination (up to Day 560) ]
  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 First Occurrence of Molecularly Confirmed Severe/Critical Coronavirus Disease (COVID-19) With Seronegative Status (Open-label Booster Vaccination Phase) [ Time Frame: 14 days after booster vaccination (Day 379) to end of study (up to 2 years and 3 month) ]
  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.
• Number of Participants With First Occurrence of Molecularly Confirmed Severe/Critical Coronavirus Disease (COVID-19) With Seronegative Status (Open-label Booster Vaccination Phase) [ Time Frame: 28 days after booster vaccination (Day 393) to end of study (up to 2 years and 3 month) ]
  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.

Original Primary Outcome Measures (submitted: August 7, 2020)

Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical Coronavirus Disease (COVID-19) with Seronegative Status [ Time Frame: Up to 2.1 years ]

Moderate defined as one sign and one symptom from a list of signs, such as respiratory rate >90 and symptoms such as shortness of breath or cough or 2 symptoms from a list of symptoms or Severe COVID-19 defined in FDA guidance.

Current Secondary Outcome Measures (submitted: April 11, 2022)

• Number of Participants With First Occurrence of Molecularly Confirmed Severe/Critical COVID-19 With Seronegative Status (Main Study) [ Time Frame: 14 Days after double-blind vaccination (Day 15) ]
  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.
• Number of Participants With First Occurrence of Molecularly Confirmed Severe/Critical COVID-19 With Seronegative Status (Main Study) [ Time Frame: 28 Days after double-blind vaccination (Day 29) ]
  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.
• Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of Their Serostatus (Main Study) [ Time Frame: 1 Day after double-blind vaccination (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.
• Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of Their Serostatus (Main Study) [ Time Frame: 14 days after double-blind vaccination (Day 15) ]
  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 First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of Their Serostatus (Main Study) [ Time Frame: 28 days after double-blind vaccination (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 First Occurrence of COVID-19 Requiring Medical Intervention (Main Study) [ Time Frame: 14 days after double-blind vaccination (Day 15) ]
  Number of participants with first occurrence of COVID-19 requiring medical intervention (such as a composite endpoint of hospitalization, ICU admission, mechanical ventilation, and extracorporeal membrane oxygenation [ECMO], linked to objective measures such as decreased oxygenation, X-ray or computed tomography [CT] findings) or linked to any molecularly confirmed, COVID-19 at least 14 days post vaccination were reported.
• Number of Participants With First Occurrence of COVID-19 Requiring Medical Intervention (Main Study) [ Time Frame: 28 Days after double-blind vaccination (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.
• 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 (Main Study) [ Time Frame: 14 Days after double-blind vaccination (Day 15) ]
  The viral load of SARS-CoV-2 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 Mild COVID-19 (Main Study) [ Time Frame: 14 Days after double-blind vaccination (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 First Occurrence of Molecularly Confirmed Mild COVID-19 (Main Study) [ Time Frame: 28 Days after double-blind vaccination (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 First Occurrence of Molecularly Confirmed COVID-19 Defined by the US Food and Drug Administration (FDA) Harmonized Case Definition (Main Study) [ Time Frame: 14 Days after double-blind vaccination (Day 15) ]
  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 First Occurrence of Molecularly Confirmed COVID-19 Defined by the US Food and Drug Administration (FDA) Harmonized Case Definition (Main Study) [ Time Frame: 28 Days after double-blind vaccination (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 Burden of Disease (BOD) Based on First Occurrence of Molecularly Confirmed Symptomatic COVID-19 (Main Study) [ Time Frame: 14 Days after double-blind vaccination (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 Participant With BOD Based on First Occurrence of Molecularly Confirmed Symptomatic COVID-19 (Main Study) [ Time Frame: 28 Days after double-blind vaccination (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 SARS-CoV-2 Seroconversion Based on Antibodies to N Protein Using ELISA and/or SARS-CoV-2 Immunoglobulin Assay (Main Study) [ Time Frame: From Day 29 until end of double-blind phase (up to 284 days after first vaccination) ]
  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 Asymptomatic Infection Detected by RT-PCR at the Time of the Month 6/Unblinding Visit (Main Study) [ Time Frame: 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 SARS-CoV-2 Infection (Serologically and/or Molecularly Confirmed) (Main Study) [ Time Frame: 28 Days after double-blind vaccination (Day 29) ]
  Number of participants with first occurrence of SARS-CoV-2 infection (serologically and/or molecularly confirmed) were reported.
• Number of Participants With Serious Adverse Events (SAEs) (Main Study) [ Time Frame: Up to 35 weeks ]
  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 Adverse Events of Special Interest (AESI) (Main Study) [ Time Frame: 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 Medically-Attended Adverse Events (MAAEs) (Main Study) [ Time Frame: Up to 6 months after double-blind vaccination on Day 1 ]
  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 MAAEs Leading to Study Discontinuation (Main Study) [ Time Frame: 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 (Main Study) [ Time Frame: Up to Day 8 (7 Days after double-blind vaccination on Day 1) ]
  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 (Main Study) [ Time Frame: Up to Day 8 (7 Days after double-blind vaccination on Day 1) ]
  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 Unsolicited AEs During 28 Days Post-vaccination (Main Study) [ Time Frame: Up to Day 29 (28 Days after double-blind vaccination on Day 1) ]
  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 (Main Study) [ Time Frame: 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).

Original Secondary Outcome Measures (submitted: August 7, 2020)

• Number of Participants with First Occurrence of Molecularly confirmed Moderate to Severe/Critical COVID-19 Regardless of their Serostatus [ Time Frame: Up to 2.1 years ]
  Moderate defined as one sign and one symptom from a list of signs, such as respiratory rate >90 and symptoms such as shortness of breath or cough or 2 symptoms from a list of symptoms or Severe COVID-19 defined in FDA guidance.
• Number of Participants with First Occurrence of Molecularly confirmed Moderate to Severe/Critical Coronavirus Disease COVID-19 with Seronegative Status [ Time Frame: Day 2 (1 day post-vaccination) ]
  Moderate defined as one sign and one symptom from a list of signs, such as respiratory rate >90 and symptoms such as shortness of breath or cough or 2 symptoms from a list of symptoms or Severe COVID-19 defined in FDA guidance.
• Number of Participants with First Occurrence of COVID-19 Requiring Medical Intervention [ Time Frame: Day 29 (28 days post- vaccination) ]
  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 or CT findings) or linked to any molecularly confirmed, COVID-19 at least 28 days post vaccination will be reported.
• 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 [ Time Frame: Day 29 (28 days post vaccination) ]
  The viral load of 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.
• Number of Participants with First Occurrence of Molecularly confirmed Mild COVID-19 [ Time Frame: Day 29 (28 days post vaccination) ]
  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.
• Number of Participants with First Occurrence of Molecularly confirmed COVID-19 Defined by the US Food and Drug Administration (FDA) Harmonized case Definition [ Time Frame: Day 29 (28 days post vaccination) ]
  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.
• Number of Participants with First Occurrence of Molecularly Confirmed COVID-19 with any Severity (Moderate, Mild, Severe/Critical) [ Time Frame: Day 29 (28 days post vaccination) ]
  Number of participants with first occurrence of molecularly confirmed COVID-19 with any severity (Moderate, Mild, severe/Critical) will be reported.
• Serologic Conversion Between Baseline and 1- year Post-vaccination using an Enzyme-linked Immunosorbent Assay (ELISA) [ Time Frame: Between baseline and 1-year post-vaccination (up to 52 weeks) ]
  Serologic conversion between baseline and 1 year post-vaccination using an ELISA and/or SARS-CoV- 2 immunoglobulin assay that is dependent on the SARS-CoV-2 nucleocapsid (N) protein will be reported.
• Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Up to 104 weeks ]
  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.
• Number of Participants with Medically-Attended Adverse Events (MAAEs) [ Time Frame: Up to 6 months ]
  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.
• Number of Participants with Medically-Attended Adverse Events (MAAEs) Leading to Study Discontinuation [ Time Frame: Up to 104 weeks ]
  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.
• Number of Participants with Solicited Local Adverse Events (AEs) During 7 Days after Vaccination [ Time Frame: Up to Day 8 (7 Days after first vaccination on Day 1) ]
  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-vaccination (day of vaccination and the subsequent 7 days).
• Number of Participants with Solicited Systemic AEs During 7 Days After Vaccination [ Time Frame: Up to Day 8 (7 Days after first vaccination on Day 1) ]
  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 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-vaccination (day of vaccination and the subsequent 7 days), for the following events: fatigue, headache, nausea, myalgia.
• Number of Participants with Unsolicited Local Adverse Events (AEs) During 28 Days Post-vaccination [ Time Frame: Up to Day 29 (28 days after first vaccination on Day 1) ]
  Unsolicited AEs are all AEs for which the participant is not specifically questioned in the participant diary.
• SARS-CoV-2 Neutralizing Antibody Titers as Assessed by Virus Neutralization Assay (VNA) [ Time Frame: Up to 104 weeks ]
  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
• SARS-CoV-2 Binding Antibodies Assessed by ELISA [ Time Frame: Up to 104 weeks ]
  SARS-CoV-2 binding antibodies as assessed by enzyme-linked immunosorbent assay (ELISA) to measure humoral immune response will be reported.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-Mediated COVID-19 in Adult Participants
• Official Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Participants With or Without Stable Co-morbidities Associated With Progression to Severe COVID-19 at Different Stages of the Protocol

Intervention

• Biological: Ad26.COV2.S
  Ad26.COV2.S will be administered at a single dose of 5*10^10 virus particles (vp) on Day 1 (or Month 6 for placebo recipients) and as a single booster dose at Year 1.
  Other Names:

  • JNJ-78436735
  • Ad26COVS1
• Other: Placebo
  Participants will receive Placebo.

Study Arms

• Experimental: 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.
  Intervention: Biological: Ad26.COV2.S
• Experimental: 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.
  Interventions:

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

Publications *

• Sadoff J, Gray G, Vandebosch A, Cardenas V, Shukarev G, Grinsztejn B, Goepfert PA, Truyers C, Van Dromme I, Spiessens B, Vingerhoets J, Custers J, Scheper G, Robb ML, Treanor J, Ryser MF, Barouch DH, Swann E, Marovich MA, Neuzil KM, Corey L, Stoddard J, Hardt K, Ruiz-Guinazu J, Le Gars M, Schuitemaker H, Van Hoof J, Struyf F, Douoguih M; ENSEMBLE Study Group. Final Analysis of Efficacy and Safety of Single-Dose Ad26.COV2.S. N Engl J Med. 2022 Mar 3;386(9):847-860. doi: 10.1056/NEJMoa2117608. Epub 2022 Feb 9.
• Sadoff J, Struyf F, Douoguih M. A plain language summary of how well the single-dose Janssen vaccine works and how safe it is. Future Virol. 2021 Nov;16(11):725-739. doi: 10.2217/fvl-2021-0199. Epub 2021 Nov 1.
• Sadoff J, Gray G, Vandebosch A, Cardenas V, Shukarev G, Grinsztejn B, Goepfert PA, Truyers C, Fennema H, Spiessens B, Offergeld K, Scheper G, Taylor KL, Robb ML, Treanor J, Barouch DH, Stoddard J, Ryser MF, Marovich MA, Neuzil KM, Corey L, Cauwenberghs N, Tanner T, Hardt K, Ruiz-Guinazu J, Le Gars M, Schuitemaker H, Van Hoof J, Struyf F, Douoguih M; ENSEMBLE Study Group. Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19. N Engl J Med. 2021 Jun 10;384(23):2187-2201. doi: 10.1056/NEJMoa2101544. Epub 2021 Apr 21.
• Williams TC, Burgers WA. SARS-CoV-2 evolution and vaccines: cause for concern? Lancet Respir Med. 2021 Apr;9(4):333-335. doi: 10.1016/S2213-2600(21)00075-8. Epub 2021 Jan 29. No abstract available.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 25, 2021): 44325
• Original Estimated Enrollment (submitted: August 7, 2020): 60000
• Actual Study Completion Date: March 31, 2023
• Actual Primary Completion Date: March 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Brazil, Chile, Colombia, Mexico, Peru, South Africa, United States
• Removed Location Countries: Philippines, Ukraine

Administrative Information

• NCT Number: NCT04505722
• Other Study ID Numbers: CR108876; VAC31518COV3001 ( Other Identifier: Janssen Vaccines & Prevention B.V. )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Vaccines & Prevention B.V.
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Vaccines & Prevention B.V.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Vaccines & Prevention B.V. Clinical Trial; Janssen Vaccines & Prevention B.V.

• PRS Account: Janssen Vaccines & Prevention B.V.
• Verification Date: May 2023