Design and analysis considerations for early phase clinical trials in hepatitis B (HBV) cure research: the ACTG A5394 study in persons with both HIV and HBV

Minhee Kang; Jennifer C Price; Marion G Peters; Sharon R Lewin; Mark Sulkowski

doi:10.1016/j.jve.2023.100344

Design and analysis considerations for early phase clinical trials in hepatitis B (HBV) cure research: the ACTG A5394 study in persons with both HIV and HBV

J Virus Erad. 2023 Aug 24;9(3):100344. doi: 10.1016/j.jve.2023.100344. eCollection 2023 Sep.

Authors

Minhee Kang¹, Jennifer C Price², Marion G Peters³, Sharon R Lewin^{4

5

6}, Mark Sulkowski⁷

Affiliations

¹ Center for Biostatistics in AIDS Research in the Department of Biostatistics, Harvard T.H. Chan School of Public Health, United States.
² Division of Gastroenterology, University of California San Francisco School of Medicine, United States.
³ Department of Medicine, Feinberg School of Medicine, Northwestern University, United States.
⁴ Department of Infectious Diseases, The University of Melbourne, Australia.
⁵ Victorian Infectious Diseases Service, Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity, Australia.
⁶ Department of Infectious Diseases, Alfred Health and Monash University, Australia.
⁷ Division of Infectious Diseases, Johns Hopkins University School of Medicine, United States.

Abstract

With growing interest and efforts to achieve a hepatitis B (HBV) cure, HBV therapeutics have increasingly entered the clinical testing phase. In designing an early phase clinical trial aimed at HBV cure, the heterogeneity in participants and the choice of a biomarker endpoint that signals a cure requires careful consideration. We describe the key elements to consider during the development of HBV clinical trials aimed at a functional cure, and how we have addressed them in the design of a phase II AIDS Clinical Trials Group (ACTG) study, A5394 (NCT05551273). The trial we present is for persons with both HIV and HBV, a unique population that has much to gain from an HBV cure. Our decisions on the design elements are specific to the study agent and the targeted population, but our deliberations may be informative in the emerging field of early phase HBV trials aimed at cure.

Keywords: Clinical trial design; Cure; HBV; HIV; Placebo; TLR agonist.

Abstract

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