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

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

— ENSEMBLE 2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04614948
• Other study ID #: CR108916
• Secondary ID: 2020-003643-29VA
• Status: Completed
• Phase: Phase 3
• Start date: November 12, 2020
• Est. completion date: June 18, 2023

Study information

• Verified date: May 2024
• Source: Janssen Vaccines & Prevention B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31831
• Est. completion date: June 18, 2023
• Est. primary completion date: June 18, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Contraceptive (birth control) use should be consistent with local regulations regarding the acceptable methods of contraception for those participating in clinical studies
• All participants of childbearing potential must: have a negative highly sensitive urine pregnancy test at screening; and have a negative highly sensitive urine pregnancy test immediately prior to each study vaccine administration
• Participant agrees to not donate bone marrow, blood, and blood products from the first study vaccine administration until 3 months after receiving the last dose of study vaccine
• Must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study
• Must be able to read, understand, and complete questionnaires in the electronic clinical outcome assessment (eCOA) (that is, the coronavirus disease-2019 [COVID 19] signs and symptoms surveillance question, the e-Diary, and the electronic patient-reported outcomes (ePROs)

Exclusion Criteria:

• Participant has a clinically significant acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or temperature greater than or equal to (>=) 38.0 degree Celsius (100.4-degree Fahrenheit) within 24 hours prior to the planned first dose of study vaccine; randomization at a later date is permitted at the discretion of the investigator and after consultation with the sponsor
• Participant has a known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or their excipients
• Participant received or plans to receive: (a) licensed live attenuated vaccines - within 28 days before or after planned administration of study vaccine; and (b) other licensed (not live) vaccines - within 14 days before or after planned administration of study vaccine
• Participant previously received a coronavirus vaccine
• Participant received an investigational drug within 30 days (including investigational drugs for prophylaxis of COVID-19) or used an invasive investigational medical device within 30 days or received investigational immunoglobulin (Ig) or investigational monoclonal antibodies within 3 months, or received convalescent serum for COVID-19 treatment within 4 months or received an investigational vaccine (including investigational Adenoviral-vectored vaccines) within 6 months before the planned administration of the first dose of study vaccine or is currently enrolled or plans to participate in another investigational study during the course of this study

Related Conditions & MeSH terms

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

Intervention

Biological:
• Ad26.COV2.S
Ad26.COV2.S vaccine will be administered on Day 1 and Day 57 in the double-blind phase. At unblinding visit Ad26.COV2.S vaccine will be administered to participants at Day 57 who have not yet received second vaccination and in newly enrolled participants as either single dose on Day 1 or two doses on Day 1 and Day 57. Single dose of Ad26.COV2.S vaccine will also be administered to participants initially receiving placebo. Single booster dose of Ad26.COV2.S vaccine will be given to participants in the open label phase who have received only a single vaccination with Ad26.COV2.S.

Other:
• Placebo
Placebo will be administered as IM injection on Day 1 and Day 57.

Locations

Country	Name	City	State
Belgium	Anima	Alken
Belgium	Institute of Tropical Medicine Antwerp	Antwerpen
Belgium	Center for Vaccinology (CEVAC)	Gent
Belgium	UZ Leuven	Leuven
Belgium	Az Sint-Maarten	Mechelen
Belgium	Private Practice RESPISOM Namur	Namur
Brazil	Hospital Nossa Senhora da Conceicao S A	Porto Alegre
Brazil	Instituto Nacional de Infectologia Evandro Chagas (INI) - FIOCRUZ	Rio de Janeiro
Brazil	Ministerio da Saude - Hospital dos Servidores do Estado - RJ	Rio de Janeiro
Brazil	Centro de Referencia E Treinamento Dst/Aids	Sao Paulo
Brazil	Instituto de infectologia Emilio Ribas	Sao Paulo
Colombia	Fundacion Cardiomet CEQUIN	Armenia
Colombia	IPS Centro Cientifico Asisitencial Jose Luis Accini S.A.S.	Barranquilla
Colombia	Asistencia Cientifica de Alta Complejidad S.A.S	Bogota
Colombia	Centro Medico Imbanaco de Cali S.A.	Cali
Colombia	T Y C Inversiones S A S Grupsalud	Santa Marta
France	CHU de Montpellier, Hopital Saint-Eloi	Montpellier
France	Hopital Cochin	Paris
France	Hopital Saint-Antoine	Paris Cedex 12
France	Groupe Hospitalier Sud Hôpital Haut-Leveque Service d'hematologie	Pessac
France	CHU Saint Etienne Hopital Nord	Saint-Etienne Cedex 2
France	Hopital Rangueil	Toulouse
France	Hopital Purpan	Toulouse Cedex 09
France	Hôpital de Brabois Adultes	Vandoeuvre les Nancy
Germany	Klinikum rechts der Isar der TU Munchen	München
Philippines	Riverside Medical Center	Bacolod
Philippines	West Visayas State University Medical Center	Iloilo City
Philippines	Tropical Disease Foundation	Makati
Philippines	Makati Medical Center	Manila
Philippines	Medical Center Manila	Manila
South Africa	Centre of Tuberculosis Research Innovation	Cape Town
South Africa	TREAD Research Tygerberg Hospital	Cape Town
South Africa	Worthwhile Clinical trials	Johannesburg
South Africa	Peermed Clinical Trial Centre	Kempton Park
South Africa	Dr AA Mahomed Medical Centre	Moloto
South Africa	VX Pharma	Pretoria
South Africa	Dr J.M. Engelbrecht Trial Site	Somerset West
South Africa	Be Part Yoluntu Centre	Western Cape
Spain	Hosp. Univ. Germans Trias I Pujol	Badalona
Spain	Hosp. Clinic de Barcelona	Barcelona
Spain	Hosp. Quiron Barcelona	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Clinica Univ. de Navarra	Madrid
Spain	Hosp. Quiron Madrid Pozuelo	Madrid
Spain	Hosp. Univ. de La Paz	Madrid
Spain	Hosp. Univ. de La Princesa	Madrid
Spain	Clinica Univ. de Navarra	Pamplona
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Powys Teaching Local Health Board - Bronllys Hospital	Brecon
United Kingdom	Brighton & Sussex University Hospitals NHS Trust	Brighton
United Kingdom	University Hospitals Bristol NHS Trust	Bristol
United Kingdom	Cambridge University Hospitals NHS Foundation Trust	Cambridge
United Kingdom	Ninewells Hospital	Dundee
United Kingdom	Royal Free Hospital	Hampstead
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	Imperial College London and Imperial College Healthcare NHS Trust	London
United Kingdom	Guy's and St Thomas' Hospital	London,
United Kingdom	Central Manchester University Hospitals NHS Foundation Trust	Manchester
United Kingdom	Newcastle upon Tyne Hospitals NHS Foundation Trust	Newcastle upon Tyne
United Kingdom	University of Oxford	Oxford
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield
United Kingdom	Southampton General Hospital	Southampton
United States	Medpharmics, LLC	Albuquerque	New Mexico
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	JEM Research LLC	Atlantis	Florida
United States	Hassman Research Institute, LLC.	Berlin	New Jersey
United States	Synexus Clinical Research US Inc	Cerritos	California
United States	Medical University of South Carolina	Charleston	South Carolina
United States	American Health Network, LLC	Charlotte	North Carolina
United States	Great Lakes Clinical Trials	Chicago	Illinois
United States	The University Of Chicago Medicine	Chicago	Illinois
United States	eStudySite	Chula Vista	California
United States	CTI Clinical Trial and Consulting Services	Cincinnati	Ohio
United States	Prestige Clinical Research Center, Inc.	Coral Gables	Florida
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	Henry Ford Health Systems	Detroit	Michigan
United States	Accel Research Sites	Eatonton	Georgia
United States	Centennial Medical Group	Elkridge	Maryland
United States	Meridian Clinical Research, LLC	Endwell	New York
United States	Regional Clinical Research, Inc.	Endwell	New York
United States	Cherry Street Services, Inc.	Grand Rapids	Michigan
United States	Velocity Clinical Research, Hallandale Beach	Hallandale Beach	Florida
United States	Centex Studies, Inc.	Houston	Texas
United States	Centex Studies, Inc.	Houston	Texas
United States	Texas Center for Drug Development Inc	Houston	Texas
United States	Health Awareness inc.	Jupiter	Florida
United States	Centex Studies, Inc.	Lake Charles	Louisiana
United States	Altus Research, Inc	Lake Worth	Florida
United States	University of Kentucky	Lexington	Kentucky
United States	Woodland International Research Group	Little Rock	Arkansas
United States	Ark Clinical Research	Long Beach	California
United States	Anthony Mills Medical, Inc	Los Angeles	California
United States	Centex Studies, Inc.	McAllen	Texas
United States	Compass Research, Melbourne	Melbourne	Florida
United States	Suncoast Research Group	Miami	Florida
United States	Coastal Carolina Research Center	Mount Pleasant	South Carolina
United States	Centennial Medical Center	Nashville	Tennessee
United States	Jersey Shore University Medical Center	Neptune	New Jersey
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Heartland Research Associates, LLC	Newton	Kansas
United States	Alliance for Multispeciality Research	Norfolk	Virginia
United States	Behavioral Clinical Research , Inc	North Miami	Florida
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Clinical NeuroScience Solutions Inc	Orlando	Florida
United States	Central Phoenix Medical Clinic	Phoenix	Arizona
United States	Hope Research Institute	Phoenix	Arizona
United States	Progressive Medical Research	Port Orange	Florida
United States	Allergy Asthma Immunology of Rochester, PC (AAIR) - Research Center	Rochester	New York
United States	Meridian Clinical Research, LLC	Rockville	Maryland
United States	Optimal Research	Rockville	Maryland
United States	Benchmark Research	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Meridien Research	Saint Petersburg	Florida
United States	JBR Clinical Research	Salt Lake City	Utah
United States	Endeavor Clinical Trials, LLC	San Antonio	Texas
United States	Artemis Institute for Clinical Research	San Diego	California
United States	The South Bend Clinic Center for Research	South Bend	Indiana
United States	Richmond Behavioral Associates	Staten Island	New York
United States	Quality of Life Medical & Research Center, LLC	Tucson	Arizona
United States	Synexus Clinical Research US Inc	Tucson	Arizona
United States	Achieve Clinical Research, LLC	Vestavia Hills	Alabama
United States	Tranquility Clinical Research	Webster	Texas
United States	Palm Beach Research Center	West Palm Beach	Florida
United States	Paradigm Clinical Research Centers, Inc.	Wheat Ridge	Colorado
United States	Wilmington Health Associates	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Vaccines & Prevention B.V.

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Colombia,  France,  Germany,  Philippines,  South Africa,  Spain,  United Kingdom, 

Outcome

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