Clinical trial NCT04614948: A Study of Ad26.COV2.S for the Prevention of SARS-CoV-2-mediated COVID-19 in Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Participants With or Without Stable Co-morbidities Associated With Progression to Severe COVID-19
Lead sponsor: Janssen Vaccines & Prevention B.V.
Sponsor class: INDUSTRY
First posted: 2020-11-04
Enrollment: 31835
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

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 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

Primary outcomes:
measure: Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 in Seronegative Participants With Onset at Least 14 Days After the Second Vaccination
timeFrame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)
Secondary outcomes:
measure: Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of Serostatus With Onset At Least 1 Day After the First Day 1 Vaccination
timeFrame: From at least 1 day after first vaccination on Day 1 (Day 2) up to end of double blind phase (7.2 months)
measure: Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 Regardless of Serostatus With Onset at Least 14 Days After the Second Vaccination
timeFrame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)
measure: Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 in Seronegative Participants With Onset at Least 1 Day After the First Day 1 Vaccination
timeFrame: From at least 1 day after first vaccination on Day 1 (Day 2) up to end of double blind phase (7.2 months)
measure: Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 With Onset at Least 14 Days After the First Day 1 Vaccination
timeFrame: From at least 14 days after first vaccination on Day 1 (Day 15) up to end of double blind phase (7.2 months)
measure: Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed Moderate to Severe/Critical COVID-19 With Onset at Least 28 Days After the First Day 1 Vaccination
timeFrame: From at least 28 days after the first vaccination on Day 1 (Day 29) up to end of double blind phase (7.2 months)
measure: Double Blind Phase: Number of Participants With First Occurrence of COVID-19 Requiring Medical Intervention With Onset at Least 14 Days After the Second Vaccination
timeFrame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)
measure: Double Blind Phase: Area Under the Curve (AUC) of SARS-CoV-2 Viral Load as Assessed by Quantitative RT-PCR in Participants With Molecularly Confirmed Symptomatic COVID-19 With Onset at Least 14 Days After Second Vaccination
timeFrame: From Day 71 up to end of the COVID-19 episode (up to 90 days)
measure: Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed Mild COVID-19 With Onset at Least 14 Days After the Second Vaccination
timeFrame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)
measure: Double Blind Phase: Number of Participants With First Occurrence of Molecularly Confirmed COVID-19 Defined by the US FDA Harmonized Case Definition With Onset at Least 14 Days After the Second Vaccination
timeFrame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)
measure: Double Blind Phase: Number of Participants With Burden of Disease (BOD) Based on First Occurrence of Molecularly Confirmed Symptomatic COVID-19 With Onset at Least 14 Days After the Second Vaccination
timeFrame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)
measure: Double Blind Phase: Number of Participants With Serologic Conversion Between Day 71 up to Unblinding Visit Using an Enzyme-linked Immunosorbent Assay (ELISA)
timeFrame: From Day 71 up to unblinding visit (7.2 months)
measure: Double Blind Phase: Number of Participants With Asymptomatic Infection Detected By Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) With Onset at Least 14 Days After the Second Vaccination
timeFrame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)
measure: Double Blind Phase: Number of Participants With First Occurrence of SARS-CoV-2 Infection (Serologically and/or Molecularly Confirmed) With Onset at Least 14 Days After the Second Vaccination
timeFrame: From at least 14 days after second vaccination on Day 57 (Day 71) up to end of double blind phase (7.2 months)
measure: Double Blind Phase: Number of Participants With Serious Adverse Events (SAEs)
timeFrame: From Day 1 up to end of double blind phase (7.2 months)
measure: Double Blind Phase: Number of Participants With Adverse Events of Special Interest (AESIs)
timeFrame: From Day 1 up to end of double blind phase (7.2 months)
measure: Double Blind Phase: Number of Participants With Medically-Attended Adverse Events (MAAEs)
timeFrame: From Day 1 up to 7.2 months
measure: Double-Blind: Number of Participants With MAAEs Leading to Study Discontinuation
timeFrame: From Day 1 up to end of double blind phase (7.2 months)
measure: Double Blind Phase: Number of Participants With Solicited Local Adverse Events (AEs) During 7 Days Following Each Vaccination
timeFrame: 7 days after first vaccination on Day 1 (up to Day 8), 7 days after second vaccination on Day 57 (up to Day 64)
measure: Double Blind Phase: Number of Participants With Solicited Systemic AEs During 7 Days Following Each Vaccination
timeFrame: 7 days after first vaccination on Day 1 (up to Day 8), 7 days after second vaccination on Day 57 (up to Day 64)
measure: Double Blind Phase: Number of Participants With Unsolicited Adverse Events (AEs) During 28 Days Post Each Vaccination
timeFrame: 28 days after first vaccination on Day 1 (up to Day 29), 28 days after second vaccination on Day 57 (up to Day 85)
measure: Double Blind Phase: SARS-CoV-2 Binding Antibodies Assessed by ELISA
timeFrame: At Baseline (Day 1), Days 29, 57 and 71
Other outcomes:
Locations:
city: Vestavia Hills
country: United States
facility: Achieve Clinical Research, LLC
state: Alabama
city: Phoenix
country: United States
facility: Hope Research Institute
state: Arizona
city: Phoenix
country: United States
facility: Central Phoenix Medical Clinic
state: Arizona
city: Tucson
country: United States
facility: Quality of Life Medical & Research Center, LLC
state: Arizona
city: Tucson
country: United States
facility: Synexus Clinical Research US Inc
state: Arizona
city: Little Rock
country: United States
facility: Woodland International Research Group
state: Arkansas
city: Cerritos
country: United States
facility: Synexus Clinical Research US Inc
state: California
city: Chula Vista
country: United States
facility: eStudySite
state: California
city: Long Beach
country: United States
facility: Ark Clinical Research
state: California
city: Los Angeles
country: United States
facility: Anthony Mills Medical, Inc
state: California
city: Sacramento
country: United States
facility: Benchmark Research
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research
state: California
city: Wheat Ridge
country: United States
facility: Paradigm Clinical Research Centers, Inc.
state: Colorado
city: Atlantis
country: United States
facility: JEM Research LLC
state: Florida
city: Coral Gables
country: United States
facility: Prestige Clinical Research Center, Inc.
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Hallandale Beach
country: United States
facility: Velocity Clinical Research, Hallandale Beach
state: Florida
city: Jupiter
country: United States
facility: Health Awareness inc.
state: Florida
city: Lake Worth
country: United States
facility: Altus Research, Inc
state: Florida
city: Melbourne
country: United States
facility: Compass Research, Melbourne
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group
state: Florida
city: North Miami
country: United States
facility: Behavioral Clinical Research , Inc
state: Florida
city: Orlando
country: United States
facility: Clinical NeuroScience Solutions Inc
state: Florida
city: Port Orange
country: United States
facility: Progressive Medical Research
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Research
state: Florida
city: West Palm Beach
country: United States
facility: Palm Beach Research Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Eatonton
country: United States
facility: Accel Research Sites
state: Georgia
city: Chicago
country: United States
facility: The University Of Chicago Medicine
state: Illinois
city: Chicago
country: United States
facility: Great Lakes Clinical Trials
state: Illinois
city: South Bend
country: United States
facility: The South Bend Clinic Center for Research
state: Indiana
city: Newton
country: United States
facility: Heartland Research Associates, LLC
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Lake Charles
country: United States
facility: Centex Studies, Inc.
state: Louisiana
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Elkridge
country: United States
facility: Centennial Medical Group
state: Maryland
city: Rockville
country: United States
facility: Optimal Research
state: Maryland
city: Rockville
country: United States
facility: Meridian Clinical Research, LLC
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health Systems
state: Michigan
city: Grand Rapids
country: United States
facility: Cherry Street Services, Inc.
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Berlin
country: United States
facility: Hassman Research Institute, LLC.
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: Medpharmics, LLC
state: New Mexico
city: Endwell
country: United States
facility: Meridian Clinical Research, LLC
state: New York
city: Endwell
country: United States
facility: Regional Clinical Research, Inc.
state: New York
city: Rochester
country: United States
facility: Allergy Asthma Immunology of Rochester, PC (AAIR) - Research Center
state: New York
city: Staten Island
country: United States
facility: Richmond Behavioral Associates
state: New York
city: Charlotte
country: United States
facility: American Health Network, LLC
state: North Carolina
city: Wilmington
country: United States
facility: Wilmington Health Associates
state: North Carolina
city: Cincinnati
country: United States
facility: CTI Clinical Trial and Consulting Services
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Nashville
country: United States
facility: Centennial Medical Center
state: Tennessee
city: Houston
country: United States
facility: Centex Studies, Inc.
state: Texas
city: Houston
country: United States
facility: Centex Studies, Inc.
state: Texas
city: Houston
country: United States
facility: Texas Center for Drug Development Inc
state: Texas
city: McAllen
country: United States
facility: Centex Studies, Inc.
state: Texas
city: San Antonio
country: United States
facility: Endeavor Clinical Trials, LLC
state: Texas
city: Webster
country: United States
facility: Tranquility Clinical Research
state: Texas
city: Salt Lake City
country: United States
facility: JBR Clinical Research
state: Utah
city: Norfolk
country: United States
facility: Alliance for Multispeciality Research
state: Virginia
city: Alken
country: Belgium
facility: Anima
city: Antwerpen
country: Belgium
facility: Institute of Tropical Medicine Antwerp
city: Gent
country: Belgium
facility: Center for Vaccinology (CEVAC)
city: Leuven
country: Belgium
facility: UZ Leuven
city: Mechelen
country: Belgium
facility: Az Sint-Maarten
city: Namur
country: Belgium
facility: Private Practice RESPISOM Namur
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao S A
city: Rio de Janeiro
country: Brazil
facility: Ministerio da Saude - Hospital dos Servidores do Estado - RJ
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Infectologia Evandro Chagas (INI) - FIOCRUZ
city: Sao Paulo
country: Brazil
facility: Instituto de infectologia Emilio Ribas
city: Sao Paulo
country: Brazil
facility: Centro de Referencia E Treinamento Dst/Aids
city: Armenia
country: Colombia
facility: Fundacion Cardiomet CEQUIN
city: Barranquilla
country: Colombia
facility: IPS Centro Cientifico Asisitencial Jose Luis Accini S.A.S.
city: Bogota
country: Colombia
facility: Asistencia Cientifica de Alta Complejidad S.A.S
city: Cali
country: Colombia
facility: Centro Medico Imbanaco de Cali S.A.
city: Santa Marta
country: Colombia
facility: T Y C Inversiones S A S Grupsalud
city: Montpellier
country: France
facility: CHU de Montpellier Hopital Saint Eloi
city: Paris Cedex 12
country: France
facility: Hopital Saint-Antoine
city: Paris
country: France
facility: Hopital Cochin
city: Pessac
country: France
facility: Groupe Hospitalier Sud Hôpital Haut-Leveque Service d'hematologie
city: Saint-Etienne Cedex 2
country: France
facility: CHU Saint Etienne Hopital Nord
city: Toulouse Cedex 09
country: France
facility: Hopital Purpan
city: Toulouse
country: France
facility: Hopital Rangueil
city: Vandoeuvre les Nancy
country: France
facility: Hôpital de Brabois Adultes
city: München
country: Germany
facility: Klinikum rechts der Isar der TU Munchen
city: Bacolod
country: Philippines
facility: Riverside Medical Center
city: Iloilo City
country: Philippines
facility: West Visayas State University Medical Center
city: Makati
country: Philippines
facility: Tropical Disease Foundation
city: Manila
country: Philippines
facility: Makati Medical Center
city: Manila
country: Philippines
facility: Medical Center Manila
city: Cape Town
country: South Africa
facility: TREAD Research Tygerberg Hospital
city: Cape Town
country: South Africa
facility: Centre of Tuberculosis Research Innovation
city: Johannesburg
country: South Africa
facility: Worthwhile Clinical trials
city: Kempton Park
country: South Africa
facility: Peermed Clinical Trial Centre
city: Moloto
country: South Africa
facility: Dr AA Mahomed Medical Centre
city: Pretoria
country: South Africa
facility: VX Pharma
city: Somerset West
country: South Africa
facility: Dr J.M. Engelbrecht Trial Site
city: Western Cape
country: South Africa
facility: Be Part Yoluntu Centre
city: Badalona
country: Spain
facility: Hosp. Univ. Germans Trias I Pujol
city: Barcelona
country: Spain
facility: Hosp. Quiron Barcelona
city: Barcelona
country: Spain
facility: Hosp Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Madrid
country: Spain
facility: Hosp. Univ. de La Princesa
city: Madrid
country: Spain
facility: Clinica Univ. de Navarra
city: Madrid
country: Spain
facility: Hosp. Univ. de La Paz
city: Madrid
country: Spain
facility: Hosp. Quiron Madrid Pozuelo
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Brecon
country: United Kingdom
facility: Powys Teaching Local Health Board - Bronllys Hospital
city: Brighton
country: United Kingdom
facility: Brighton & Sussex University Hospitals NHS Trust
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Trust
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Dundee
country: United Kingdom
facility: Ninewells Hospital
city: Hampstead
country: United Kingdom
facility: Royal Free Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: Guy's and St Thomas' Hospital
city: London
country: United Kingdom
facility: Imperial College London and Imperial College Healthcare NHS Trust
city: Manchester
country: United Kingdom
facility: Central Manchester University Hospitals NHS Foundation Trust
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle upon Tyne Hospitals NHS Foundation Trust
city: Oxford
country: United Kingdom
facility: University of Oxford
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
affiliation: Janssen Vaccines & Prevention B.V.
name: Janssen Vaccines & Prevention B.V. Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Hardt K, Vandebosch A, Sadoff J, Le Gars M, Truyers C, Lowson D, Van Dromme I, Vingerhoets J, Kamphuis T, Scheper G, Ruiz-Guinazu J, Faust SN, Spinner CD, Schuitemaker H, Van Hoof J, Douoguih M, Struyf F; ENSEMBLE2 study group. Efficacy, safety, and immunogenicity of a booster regimen of Ad26.COV2.S vaccine against COVID-19 (ENSEMBLE2): results of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Infect Dis. 2022 Dec;22(12):1703-1715. doi: 10.1016/S1473-3099(22)00506-0. Epub 2022 Sep 13.