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: Recruiting
• First Posted: August 10, 2020
• Last Update Posted: December 3, 2020
• 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
• Last Update Posted Date: December 3, 2020
• Actual Study Start Date: September 7, 2020
• Estimated Primary Completion Date: March 10, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 2, 2020)

Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical Coronavirus Disease (COVID-19) with Seronegative Status [ Time Frame: 14 Days post-vaccination (Day 15) to end of study (2.1 Years) ]

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.

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: October 2, 2020)

• Number of Participants with First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of their Serostatus [ Time Frame: 1 Day post-vaccination (Day 2) to end of study (2.1 Years) ]
  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 Regardless of Their Serostatus [ Time Frame: 14 Days post-vaccination (Day 15) to end of study (2.1 Years) ]
  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) [ Time Frame: 1 Day post-vaccination (Day 2) to end of study (2.1 Years) ]
  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 [ Time Frame: 14 Days post-vaccination (Day 15) to end of study (2.1 Years) ]
  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.
• 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: 14 Days post-vaccination (Day 15) to end of study (2.1 Years) ]
  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: 14 Days post-vaccination (Day 15) to end of study (2.1 Years) ]
  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: 14 Days post-vaccination (Day 15) to end of study (2.1 Years) ]
  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 [ Time Frame: 14 Days post-vaccination (Day 15) to end of study (2.1 Years) ]
  BOD will be evaluated based on the first occurrence of molecularly confirmed COVID-19, including mild, moderate or severe/critical COVID-19 case.
• Serologic Conversion Between Baseline and (Day 1; Pre-vaccination), Day 71, 6 Months and 1- Year Post-vaccination using an Enzyme-linked Immunosorbent Assay (ELISA) [ Time Frame: Between baseline (Day 1; pre-vaccination) and Day 71, 6 Months, 1-Year post-vaccination (up to 52 Weeks) ]
  Serologic conversion between baseline and (Day 1; pre-vaccination), Day 71, 6 Months, 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 First Occurrence of SARS-CoV-2 Infection (Serologically and/or Molecularly Confirmed) [ Time Frame: 14 Days post-vaccination (Day 15) to end of study (2.1 Years) ]
  Number of participants with first occurrence of SARS-CoV-2 infection (serologically and/or molecularly confirmed) with onset at least 14 days after vaccination (Day 15) to end of Study (2.1 Years) 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 Following 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 Following 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.

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 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: 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 enroll up to 60,000 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: 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 dose level of 5*10^10 virus particles (vp) as single dose vaccine on Day 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.
  Intervention: Biological: Ad26.COV2.S
• Placebo Comparator: Placebo
  Participants will receive IM injection of placebo on Day 1.
  Intervention: Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 7, 2020): 60000
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 10, 2023
• Estimated Primary Completion Date: March 10, 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)

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) or used an invasive investigational medical device within 30 days or received investigational immunoglobulin 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: Study Contact; 844-434-4210; JNJ.CT@sylogent.com

• 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

• Responsible Party: Janssen Vaccines & Prevention B.V.
• Study Sponsor: Janssen Vaccines & Prevention B.V.
• 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: November 2020