Trial Evaluating Investigational Janssen COVID-19 Vaccine
September 23, 2020
People 18 years of age and older who are interested in participating in this trial can visit coronaviruspreventionnetwork.org or ClinicalTrials.gov and search identifier NCT04505722 for details. Please do not contact the NIAID media phone number or email to enroll in this trial.
A fourth Phase 3 clinical trial evaluating an investigational vaccine for coronavirus disease 2019 (COVID-19) has begun enrolling adult volunteers. The trial is designed to evaluate if the investigational Janssen COVID-19 vaccine (JNJ-78436725) can prevent symptomatic COVID-19 after a single dose regimen. Up to 60,000 volunteers will be enrolled in the trial at up to nearly 215 clinical research sites in the United States and internationally.
The Janssen Pharmaceutical Companies of Johnson & Johnson developed the investigational vaccine (also known as Ad.26.COV2.S) and is leading the clinical trial as regulatory sponsor. Janssen, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response, are funding the trial.
U.S. and international trial sites part of the NIAID-supported COVID-19 Prevention Network (CoVPN) will participate in the trial. The CoVPN is composed of existing NIAID-supported clinical research networks with infectious disease expertise and designed for rapid and thorough evaluation of vaccine candidates and monoclonal antibodies for the prevention of COVID-19.
“Four COVID-19 vaccine candidates are in Phase 3 clinical testing in the United States just over eight months after SARS-CoV-2 was identified. This is an unprecedented feat for the scientific community made possible by decades of progress in vaccine technology and a coordinated, strategic approach across government, industry and academia,” said NIAID Director Anthony S. Fauci, M.D. “It is likely that multiple COVID-19 vaccine regimens will be required to meet the global need. The Janssen candidate has showed promise in early-stage testing and may be especially useful in controlling the pandemic if shown to be protective after a single dose.”
The Janssen vaccine candidate is a recombinant vector vaccine that uses a human adenovirus to express the SARS-CoV-2 spike protein in cells. Adenoviruses are a group of viruses that cause the common cold. However, the adenovirus vector used in the vaccine candidate has been modified so that it can no longer replicate in humans and cause disease. Janssen uses the same vector in the first dose of its prime-boost vaccine regimen against Ebola virus disease (Ad26.ZEBOV and MVA-BN-Filo) that was recently granted marketing authorization by the European Commission.
Preclinical findings published in Nature show that the investigational Janssen COVID-19 vaccine induced neutralizing antibody responses in rhesus macaques and provided complete or near-complete protection against virus infection in the lungs and nose following SARS-CoV-2 challenge. The safety, reactogenicity and immunogenicity of the investigational vaccine are being evaluated in a Phase 1/2a trial in the United States and Belgium enrolling adult volunteers. Positive interim results from the Phase 1/2a clinical study demonstrated that the safety profile and immunogenicity after a single vaccination were supportive of further development.
“Scientific partners from government, industry and academia are working hand-in-hand to develop safe, effective vaccines to put this pandemic in our rear-view mirror,” said NIH Director Francis S. Collins, M.D., Ph.D. “While administrative steps are being streamlined to speed the process, safety and effectiveness measures are just as rigorous than ever.”
The Phase 3 trial is being conducted in collaboration with Operation Warp Speed (OWS), a multi-agency collaboration overseen by HHS and the Department of Defense that aims to accelerate the development, manufacturing and distribution of medical countermeasures for COVID-19. OWS and CoVPN also are assisting with additional COVID-19 preventive candidate vaccines, including mRNA-1273, an investigational vaccine co-developed by NIAID and the Cambridge, Massachusetts-based biotechnology company Moderna, Inc., and AZD1222, a vaccine candidate being developed by United Kingdom-based biopharmaceutical company AstraZeneca.
“To have just one candidate vaccine in Phase 3 trials less than a year after a virus was first reported would be a remarkable accomplishment; to have four candidates at that stage is extraordinary,” said HHS Secretary Alex Azar. “By building a portfolio of candidate vaccines, Operation Warp Speed is maximizing the chances that we will have substantial supplies of a safe and effective vaccine—and maybe multiple vaccine options—by January 2021.”
The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership helped to ensure the protocols of all NIH- and OWS-supported Phase 3 trials of investigational vaccines use the same assays and are designed to evaluate the same primary objective: whether the vaccine can prevent symptomatic COVID-19. This approach enables transparent evaluation of the relative performance of each vaccine approach across trials.
Paul A. Goepfert, M.D., director of the Alabama Vaccine Research Clinic at the University of Alabama in Birmingham; Beatriz Grinsztejn, M.D., Ph.D., director of the Laboratory of Clinical Research on HIV/AIDS at the Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation in Rio de Janeiro, Brazil; and Glenda E. Gray, M.B.B.Ch., president and chief executive officer of the South African Medical Research Council and co-principal investigator of the HIV Vaccine Trials Network (HVTN), will serve as principal investigators for the Phase 3 trial of the investigational Janssen COVID-19 vaccine.
Volunteers must provide informed consent to participate in the trial. After providing a baseline nasopharyngeal and blood sample, participants will be assigned at random to receive either a single dose of the investigational vaccine or a saline placebo. The trial is blinded, meaning neither investigators nor participants will know who is receiving the investigational vaccine. Participants will be followed closely for safety and will be asked to provide additional blood samples at specified time points after the injection and over two years. Scientists will analyze the blood samples to detect and quantify immune responses to COVID-19. Of note, specialized assays will be used that can distinguish between immunity as a result of natural infection and vaccine-induced immunity.
The trial is designed primarily to determine if the investigational vaccine can prevent moderate to severe COVID-19 after a single dose. It also aims to understand if the vaccine can prevent COVID-19 requiring medical intervention and if the vaccine can prevent milder cases of COVID-19 and asymptomatic SARS-CoV-2 infection.
An independent Data and Safety Monitoring Board (DSMB) will provide oversight to ensure the safe and ethical conduct of the study. All Phase 3 clinical trials of candidate vaccines supported through Operation Warp Speed are overseen by a common DSMB developed in consultation with ACTIV.
About the COVID-19 Prevention Network: The COVID-19 Prevention Network (CoVPN) was formed by the National Institute of Allergy and Infectious Diseases (NIAID) at the U.S. National Institutes of Health to respond to the global pandemic. Through the CoVPN, NIAID is leveraging the infectious disease expertise of its existing research networks and global partners to address the pressing need for vaccines and antibodies against SARS-CoV-2. CoVPN will work to develop and conduct studies to ensure rapid and thorough evaluation of vaccines and antibodies for the prevention of COVID-19. The CoVPN is headquartered at the Fred Hutchinson Cancer Research Center. For more information about the CoVPN, visit: coronaviruspreventionnetwork.org.
About HHS, ASPR, and BARDA: HHS works to enhance and protect the health and well-being of all Americans, providing for effective health and human services and fostering advances in medicine, public health, and social services. The mission of ASPR is to save lives and protect Americans from 21st century health security threats. Within ASPR, BARDA invests in the innovation, advanced research and development, acquisition, and manufacturing of medical countermeasures – vaccines, drugs, therapeutics, diagnostic tools, and non-pharmaceutical products needed to combat health security threats. To date, BARDA-supported products have achieved 55 FDA approvals, licensures or clearances. To learn more about federal support for the nationwide COVID-19 response, visit www.coronavirus.gov.
About Operation Warp Speed: OWS is a partnership among components of the Department of Health and Human Services and the Department of Defense, engaging with private firms and other federal agencies, and coordinating among existing HHS-wide efforts to accelerate the development, manufacturing, and distribution of COVID-19 vaccines, therapeutics, and diagnostics.
About the National Institute of Allergy and Infectious Diseases: NIAID conducts and supports research—at NIH, throughout the United States, and worldwide—to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.
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Please visit clinicaltrials.gov and search identifier NCT04505722 to see all study locations. Of 214 total sites, approximately 89 sites are in the United States, 31 are in South Africa, 29 are in Brazil, and 65 are in Colombia, Mexico, Chile, Peru and Argentina.
A working group led by experts from NIAID, CoVPN and the Department of Defense is using county-level COVID-19 public health data with incidence trajectory modeling, and information about essential facilities, to identify high-incidence areas and emerging hot zones so that sites near these locations are prioritized for enrollment.
Healthy adults 18 years and older are eligible to participate in the trial. Randomization will be stratified based on age: those who are 18 to 59 years and those who are 60 years and older. Randomization will also be stratified based on presence or absence of co-morbidities associated with an increased risk of progression to severe COVID-19.
People with medically stable chronic diseases are also eligible to participate in the trial, including people with HIV who are on antiretroviral therapy. Women who are pregnant may not participate in the trial.
The trial will use a staggered enrollment strategy. Most sites will begin enrolling adults of any age without co-morbidities that are associated with increased risk of progression to severe COVID-19. Once 2,000 adults under the age of 60 are enrolled, there will be a pause to review safety data before continuing enrollment in this group and expanding to adults in this age category with co-morbidities. Once 2,000 adults 60 years or older are enrolled, there will be a pause to review safety data before continuing enrollment in this group and expanding to adults in this age category with co-morbidities.
The NIAID-funded COVID-19 Prevention Network (CoVPN) is working with stakeholders to reach priority populations, including Native Americans, Black Americans (including African Americans), the Latinx community, people who are at higher risk of exposure to SARS-CoV-2 infection due to occupation, people with pre-existing health conditions, people living in assisted living facilities and communities experiencing health disparities. This community engagement effort encompasses community education, recruitment and retention and builds on the long history of community engagement in the HIV Prevention Trials Network and the HIV Vaccine Trials Network. The CoVPN has also established an active Community Advisory Board that is assisting with messaging and outreach to highly impacted communities.
To facilitate effective outreach, the CoVPN also has established several expert panels. These include the Native and Indigenous, Black/African American, Latinx, older adult/veteran expert panels, and others that are still being formed. The panels include 10-15 scientific experts from within their respective communities who are providing their insight and expertise on the protocol, as well issues related to ethics, the significance and potential impact of the research in their communities, and they will make recommendations for broader community engagement as appropriate. The panels were established after the Moderna Phase 3 protocol was already finalized, but they will have more input on future studies.
People can say yes or no when invited to join a study. All study volunteers must go through a process called informed consent that ensures they understand potential risks and benefits of being in a study. They also may leave a study at any time. The COVID-19 Prevention Network (CoVPN) makes every effort to ensure that people understand the study fully before they decide whether to join. The Phase 3 trial of Ad.26.COV2.S follows U.S. federal regulations on research, as well as international ethical standards.
The “Operation Warp Speed” program aims to accelerate the typical vaccine development process by initiating large-scale manufacturing alongside highly coordinated clinical research to ensure timely scale up once safe and effective candidates are identified. The program will not cut corners on vaccine safety or trial integrity.
The DSMB is an independent advisory group with expertise in ethics, statistics, vaccine development, patient care and clinical trials that advise a group composed of the study sponsor, NIAID and BARDA. The DSMB reviews interim and final data on safety and efficacy and makes recommendations to the sponsor regarding whether a protocol should be amended, or the study should proceed based on its review. The DSMB can recommend the study be terminated at any time if deemed necessary.
The trial protocol and related materials also have been reviewed by the U.S. Food and Drug Administration and an Institutional Review Board (IRB). The purpose of an IRB is to ensure the rights and welfare of human research participants.
The U.S. Food and Drug Administration has published guidance for industry for the development and licensure of vaccines to prevent COVID-19. The document notes that FDA would expect that a COVID-19 vaccine candidate for licensure would prevent disease or decrease the severity of disease in at least 50% of people who are vaccinated (50% vaccine efficacy). The document also provides considerations for the issuance of an Emergency Use Authorization.
Investigators anticipate that the trial will take approximately 2 months to enroll. It is difficult to predict exactly how long it will take to generate enough data to determine the safety and efficacy of the vaccine candidate since that depends on the actual incidence, distribution and control of SARS-CoV-2. The trial is event-driven, meaning that trial statisticians estimate 154 cases of COVID-19 among trial participants will be needed for a high probability of detecting a statistically significant percent reduction in disease incidence in the vaccinated group compared to the unvaccinated placebo group.
The trial is primarily designed to evaluate if the experimental vaccine can prevent cases of COVID-19 that are classified as moderate or severe/critical. As a secondary goal, the trial also will examine if the vaccine can prevent mild cases.
Moderate COVID-19 is defined as having SARS-CoV-2 infection and at least one of the following symptoms: shortness of breath or low oxygen, pneumonia or evidence of deep vein blood clots; or at least two of the following symptoms: increased heart rate, chills, sore throat, cough, malaise, headache, muscle pain, gastrointestinal symptoms, new loss of sense of smell or taste, or red or bruised looking feet or toes.
Severe/critical COVID-19 is defined as having SARS-CoV-2 infection and any of the following:
- Clinical signs of severe systemic illness
- Respiratory failure (defined as needing high-flow oxygen, noninvasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation, known as ECMO)
- Evidence of shock
- Significant acute renal, hepatic or neurologic dysfunction or
- Admission to an intensive care unit or death
Mild COVID-19 is defined as having SARS-CoV-2 infection and one of the following symptoms: fever, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, cough, chest congestion, runny nose, wheezing, skin rash, eye irritation or discharge, chills, new loss of sense of smell or taste, red or bruised looking feet or toes or chills.