Controlled Human Infection Model for Hepatitis C Virus Vaccine Development: Trial Design Considerations.

The design of a clinical trial for a controlled human infection model (CHIM) to accelerate hepatitis C virus (HCV) vaccine development requires careful consideration. The design of a potential approach to HCV CHIM is outlined, involving initial sentinel cohorts to establish the safety and curability of the viral inoculum followed by larger cohorts to establish the spontaneous clearance rate for each inoculum. The primary endpoint would be HCV clearance by 24 weeks post-inoculation, recognizing that the prevention of chronic infection would be the primary goal of HCV vaccine candidates. Additional considerations are discussed, including the populations to be enrolled, the required monitoring approach, indications for antiviral therapy, and the required sample size for different CHIM approaches. Finally, safety considerations for CHIM participants are discussed.
Competing Interests: Potential conflicts of interest . J. B. reports funding through the Canadian Institutes of Health Research and Gilead Sciences. They also report honoraria payment for giving a presentation from Gilead Sciences. They report participation in a Data and Safety Monitoring Board (DSMB) with AbbVie, Gilead Sciences, and Cepheid Sciences and a board role with the International Network on Hepatitis and Health for Substance Abusers. D. L. T. reports research funding support from the National Institutes of Health (NIH) and National Institute on Drug Abuse (NIDA); royalties or licenses with UpToDate; consulting fees from Merck and Co, Excision Bio, and Evrys; honoraria payments from Masur et al Infectious Diseases Board Review; and participation on a DSMB with Merck and Co; and holds a leadership role with the Conference on Retroviruses and Opportunistic Infections (CROI) Program Committee and the African Mission Healthcare. G. J. D. reports clinical trial grants from Gilead Sciences, AbbVie, and Merck. They also report being an associate editor with the Journal of Hepatology. J. J. F. reports receiving a Canadian Institutes of Health Research Planning and Dissemination Grant (1183426). They report receiving grants and consulting fees from AbbVie and Gilead and is the past president of the Canadian Association for the Study of the Liver. M. S. reports receiving the NIH midcareer mentoring award, K24DA034621. They report receiving research grants to Johns Hopkins University from Janssen, Vir, Assembly Bio, and AbbVie, and also received consulting fee payments from AbbVie, Assembly Bio, Aligos Antios, Arbutus, Gilead, Precision Bio, and GSK for participation in a Scientific Advisory Board related to hepatitis V virus (HBV) and HCV. They also participated in a DSMB related to HIV and HBV with Gilead and Immunocore and is the American editor for the Journal of Viral Hepatitis. B. H. and M. G. G. report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
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