In a recent special communication report published in JAMA Network is openIn this article, researchers describe the Coronavirus Disease 2019 (COVID-19) Prevention Network (CoVPN) and its contribution to clinical efficacy evaluations of COVID-19 vaccines in Phase 3 trials.
COVID-19 has caused unprecedented illness and death around the world. The continued emergence of new SARS-CoV-2 variants has challenged severe acute respiratory syndrome effectiveness Vaccines and therapeutic agents such as monoclonal antibodies. The effects of the pandemic call for a concerted global effort to assess efficacy and safety, to aid clinical evaluations and the development of more effective and broader COVID-19 vaccines.
To facilitate the rapid development of effective SARS-CoV-2 vaccines through clinical testing and licensing of potential candidates, partnerships between government, private foundations, and academia are required to improve global vaccine research. To address these needs, CoVpN was created by NIAID (National Institute of Allergy and Infectious Diseases).
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In this study, researchers describe CoVPN in helping to coordinate the implementation of Phase III clinical vaccine efficacy trials in the development of COVID-19 vaccines.
The beginning of CoVPN
Created in April 2020, CoVPN operates in alignment with the OWS (Process Wrapper Speed) model and was formally scheduled for May 2020. The goal of CoVPN was to quickly design and run Phase III vaccine efficacy clinical trials with coordinated protocols, endpoints, and correlations with development of new vaccines for COVID-19 based on the efficacy results of several vaccine candidate prototypes under research in the United States (US).
The network aims to integrate trial sites and laboratories to compellingly evaluate all vaccine prototypes to rapidly scale clinical evaluations using existing healthcare resources. In addition, CoVPN aims to partner with several NIAID-funded trial networks, such as the HIV Vaccine Trials Network, the Infectious Disease Clinical Research Consortium, and the Acquired Immune Deficiency Syndrome (AIDS) and HIV Clinical Trials Group. . Preventive Trials Network.
As a result of CoVPN’s efforts, the five Phase 3 clinical trial sites included 16 countries across sub-Saharan regions of Africa, the United States, and South America, across five continents. In addition, in the United States, the sites of several NIAID-funded networks, such as the Native Nations, Veterans Affairs, and Department of Defense sites, are included.
CoVPN’s contribution to Phase III vaccine efficacy trials
All of the COVID-19 vaccines in the US government’s portfolio have used the SARS-CoV-2S (Spike) protein. Four studies used the spike 2/SP subunit of the pre-fusion protein structure, while the COVID-19 vaccine (Oxford/AstraZeneca) used the entire S protein as an immunogen. CoVPN has facilitated the evaluation of various vaccine platforms to diversify manufacturing supply capabilities and vaccine development based on efficacy and safety results in trial outcomes.
The five phase 3 trials were designed by the joint efforts of the statisticians at CoVPN, the WHO Solidarity Vaccine Trial Expert Group (WHO), the NIAID DSMB (Data Safety Monitoring Board), and the US Food and Drug Administration (FDA). . Concerted efforts enabled the inclusion of large sample sizes to obtain high efficacy and safety datasets and to evaluate the efficacy of vaccine candidates for SARS-CoV-2 symptomatic infections of varying severity.
The SAP (Statistical Analysis Plan) drafted by CoVPN statisticians has collaborated with the COVID-19 Response Team Statistics to provide key trial protocols for curated analyzes and non-CoVPN directed trials. Furthermore, CoVPN statisticians had access to the results of all five clinical trials, providing the opportunity to answer questions that could not be answered by any of the individual studies.
Phase III clinical trials differed in their main efficacy evaluation windows, study designs, vaccination regimens, and launch dates. Moderna’s COVE (Coronavirus Vaccine Efficacy and Safety) study and AstraZeneca’s AZD1222 study used a two-dose regimen, with doses given four weeks apart, with the efficacy window opening two weeks after the second vaccination in both clinical trials. The Janssen/Johnson & Johnson’s ENSEMBLE study evaluated a single dose of Ad26.COV2.S vaccine. The efficacy of Ad26.COV2.S vaccine was measured 2 weeks after the vaccine dose.
Novovax’s PREVENT-19 (protein perfusion subunit vaccine The Novavax COVID-19 Pilot Efficacy Study evaluated the efficacy of the NVX-CoV2373 vaccine given in two doses three weeks apart, with the efficacy window opened for one week after a second. The Sanofi Pasteur VAT0008 study assessed the efficacy of a two-dose vaccine, with doses administered three weeks apart from 21, with efficacy measurements beginning two weeks after the second vaccination.
Coordination of community outreach and fair registration efforts was aided by a check log hosted on the CoVPN website. This enabled potential participants to register and recruit on CoVPN sites in the US. Among the CoVPN-supported trials, only the PREVENT-19 trial included a blinded crossover study design. In the COVE, ENSEMBLE, and ADZ1222 studies, individuals could unblind and seek approved vaccines.
In conclusion, based on the results, CoVPN enabled Phase III vaccine efficacy trials to be conducted among geographically and demographically diverse samples, with robust statistical analysis, and alignment of clinical and laboratory endpoints across different vaccine platforms. In addition, CoVPN enabled coordinated immune correlates assessments of protection and assisted in the coordinated development of a COVID-19 vaccine candidate effective against various SARS-CoV-2 variants of concern.