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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04505722
Recruitment Status : Active, not recruiting
First Posted : August 10, 2020
Last Update Posted : October 12, 2021
Sponsor:
Information provided by (Responsible Party):
Janssen Vaccines & Prevention B.V.

Tracking Information
First Submitted Date  ICMJE July 31, 2020
First Posted Date  ICMJE August 10, 2020
Last Update Posted Date October 12, 2021
Actual Study Start Date  ICMJE September 7, 2020
Actual Primary Completion Date January 22, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 4, 2021)
  • 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) to end of study (2 years and 1 month) ]
    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 sign and 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 (Main Study) [ Time Frame: 28 Days after double-blind vaccination (Day 29) to end of study (2 years and 1 month) ]
    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 sign and symptoms or severe COVID-19 defined in 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 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-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 who will be enrolled in safety subset 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-booster vaccination (day of vaccination and the subsequent 7 days), 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 are 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 (2 years 1 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 (2 years 1 months) ]
    Number of participants with AESI will be 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) ]
    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.
  • 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) ]
    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.
  • 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 (2 years and 1 month) ]
    Severe defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 30 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.
  • 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 (2 years and 1 month) ]
    Severe defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate >= 30 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.
Original Primary Outcome Measures  ICMJE
 (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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 4, 2021)
  • Number of Participants with First Occurrence of Molecularly Confirmed Severe/Critical Coronavirus Disease (COVID-19) with Seronegative Status (Main Study) [ Time Frame: 14 Days after double-blind vaccination (Day 15) to end of study (2 years and 1 month) ]
    Severe defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate greater than or equal to (>=) 30 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.
  • Number of Participants with First Occurrence of Molecularly Confirmed Severe/Critical Coronavirus Disease (COVID-19) with Seronegative Status (Main Study) [ Time Frame: 28 Days after double-blind vaccination (Day 29) to end of study (2 years and 1 month) ]
    Severe defined as one sign or symptom from a list of signs and symptoms, such as respiratory rate greater than or equal to (>=) 30 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.
  • 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) to end of study (2 years and 1 months) ]
    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.
  • 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) up to end of study (2 years and 1 month) ]
    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.
  • 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 15) up to end of study (2 years and 1 month) ]
    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 sign and symptoms or severe COVID-19 defined in 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) up to end of study (2 years and 1 month) ]
    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 14 days post vaccination will be 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) to end of study (2 years and 1 month) ]
    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 (Main Study) [ Time Frame: 14 Days after double-blind vaccination (Day 15) to end of study (2 years and 1 month) ]
    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 (Main Study) [ Time Frame: 14 Days after double-blind vaccination (Day 15) to end of study (2 years and 1 month) ]
    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 Mild COVID-19 (Main Study) [ Time Frame: 28 Days after double-blind vaccination (Day 29) to end of study (2 years and 1 month) ]
    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 (Main Study) [ Time Frame: 14 Days after double-blind vaccination (Day 15) to end of study (2 years and 1 month) ]
    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 Defined by the US Food and Drug Administration (FDA) Harmonized case Definition (Main Study) [ Time Frame: 28 Days after double-blind vaccination (Day 29) to end of study (2 years and 1 month) ]
    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.
  • 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) to end of study (2 years and 1 month) ]
    BOD will be evaluated based on the first occurrence of molecularly confirmed COVID-19, including mild, moderate or severe/critical COVID-19 case.
  • BOD Based on First Occurrence of Molecularly Confirmed Symptomatic COVID-19 (Main Study) [ Time Frame: 28 Days after double-blind vaccination (Day 29) to end of study (2 years and 1 month) ]
    BOD will be evaluated based on the first occurrence of molecularly confirmed COVID-19, including mild, moderate or severe/critical COVID-19 case.
  • Serologic Conversions Between Baseline (Day 1; Pre-vaccination), and Day 29, between Day 29 and Day 71, between Day 71 and Month 6/Unblinding Visit and Month 18 After Double-blind vaccination using an ELISA (Main Study) [ Time Frame: Between baseline (Day 1; pre-vaccination), and Day 29, between Day 29 and Day 71, between Day 71 and Month 6 and Month 18 after double-blind vaccination (up to 78 Weeks) ]
    Serologic conversion between baseline (Day 1; Pre-vaccination), and Day 29, between Day 29 and Day 71, between Day 71 and Month 6/unblinding Visit and Month 18 after double-blind vaccination using an Enzyme-linked Immunosorbent Assay (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 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 will be 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) to end of study (2 years and 1 month) ]
    Number of participants with first occurrence of SARS-CoV-2 infection (serologically and/or molecularly confirmed) with onset at least 28 days after vaccination (Day 29) to end of Study (2 years and 1 month) will be reported.
  • Number of Participants with SAEs (Main Study) [ Time Frame: Up to 104 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 AESI (Main Study) [ Time Frame: Up to 104 Weeks ]
    Number of participants with AESIs will be 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: Day 1 after double-blind vaccination (Up to 6 months); at Month 6 after open-label vaccination (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 (Main Study) [ 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 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 will be enrolled in safety subset 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 Following Vaccination (Main Study) [ Time Frame: Up to Day 8 (7 Days after double-blind vaccination on Day 1) ]
    Participants who will be enrolled in safety subset 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 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 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) (Main Study) [ 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 (Main Study) [ 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.
  • Number of Participants with Symptomatic Severe/Critical Disease (Open-label Booster Vaccination Phase) [ Time Frame: Up to 1 year and 1 month ]
    Number of participants with symptomatic severe/critical disease will be reported.
  • Number of Participants with Hospitalization (Open-label Booster Vaccination Phase) [ Time Frame: Up to 1 year and 1 month ]
    Number of participants with hospitalization will be reported.
  • Number of Participants with Death (Open-label Booster Vaccination Phase) [ Time Frame: Up to 1 year and 1 month ]
    Number of participants with death will be reported.
  • Serological Response to Vaccination Measured by VNA (Open-label Booster Vaccination Phase) [ Time Frame: Day 393 (28 days after booster vaccination) ]
    Serological response to vaccination as measured by VNA 28 days after single-dose booster vaccination will be reported.
  • Antibody Titers Against Original SARS-CoV-2 Strain Measured by VNA (Open-label Booster Vaccination Phase) [ Time Frame: Day 393 (28 days after booster vaccination) ]
    Antibody titers against original SARS-CoV-2 strain as measured by VNA 28 days after single-dose booster vaccination will be reported.
  • Number of Participants with Binding Antibody Against Wuhan Reference Strain and Variants of Interest Measured by Wild Type VNA (wtVNA)/Pseudovirus (ps)VNA (Open-label Booster Vaccination Phase) [ Time Frame: Day 393 (28 days after booster vaccination) ]
    Number of participants with binding antibody against Wuhan reference strain and variants of interest as measured by wtVNA/psVNA will be reported.
  • Number of Participants with Neutralizing Antibody Against Wuhan Reference Strain and Variants of Interest Measured by wtVNA/psVNA (Open-label Booster Vaccination Phase) [ Time Frame: Day 393 (28 days after booster vaccination) ]
    Number of participants with binding antibody against Wuhan reference strain and variants of interest as measured by wtVNA/psVNA will be reported.
  • Number of Participants With SARS-CoV-2 Infection (Open-label Booster Vaccination Phase) [ Time Frame: Up to 1 year and 1 month ]
    Number of participants with SARS-COV-2 infection serologically and/or molecularly confirmed will be reported.
  • Platelet Count (Open-label Booster Vaccination Phase) [ Time Frame: Day 365 (Day of booster vaccination); Day 393 (28 days after booster vaccination) ]
    Platelet count on the day of booster vaccination and 28 days after booster vaccination will be reported.
  • Number of Participants with Thromboembolic Events (Open-label Booster Vaccination Phase) [ Time Frame: Day 365 (Day of booster vaccination); Day 393 (28 days after booster vaccination) ]
    Number of participants with thromboembolic events will be reported.
Original Secondary Outcome Measures  ICMJE
 (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 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) [ 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  ICMJE A Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-Mediated COVID-19 in Adult Participants
Official Title  ICMJE 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 enroll 44,325 participants in order to 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Participants With or Without Stable Co-morbidities Associated With Progression to Severe COVID-19 at Different Stages of the Protocol
Intervention  ICMJE
  • 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  ICMJE
  • 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 *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 25, 2021)
44325
Original Estimated Enrollment  ICMJE
 (submitted: August 7, 2020)
60000
Estimated Study Completion Date  ICMJE January 2, 2023
Actual Primary Completion Date January 22, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Chile,   Colombia,   Mexico,   Peru,   South Africa,   United States
Removed Location Countries Philippines,   Ukraine
 
Administrative Information
NCT Number  ICMJE NCT04505722
Other Study ID Numbers  ICMJE 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  ICMJE
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
Responsible Party Janssen Vaccines & Prevention B.V.
Study Sponsor  ICMJE Janssen Vaccines & Prevention B.V.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Janssen Vaccines & Prevention B.V. Clinical Trial Janssen Vaccines & Prevention B.V.
PRS Account Janssen Vaccines & Prevention B.V.
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP