Design and analysis considerations for early phase clinical trials in HBV cure research: ACTG A5394 example in persons with both HIV and HBV

With growing interests and efforts to achieve HBV cure, HBV therapeutics have increasingly entered the clinical phase. In designing an early phase clinical trial aimed at HBV cure, heterogeneity in HBV patients and choosing a biomarker endpoint that signals cure require careful considerations. We describe the key elements to consider during the development of HBV clinical trials aimed at functional cure, and how we 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 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.