Participants With or Without Stable Co-morbidities Associated With Progression to Severe COVID-19 Clinical Trial
— ENSEMBLE 2Official 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
| Verified date | May 2024 |
| Source | Janssen Vaccines & Prevention B.V. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| 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 |
| 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 |
| Lead Sponsor | Collaborator |
|---|---|
| Janssen Vaccines & Prevention B.V. |
United States, Belgium, Brazil, Colombia, France, Germany, Philippines, South Africa, Spain, United Kingdom,
| 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 |