IP-cure-B: evaluate novel immunomodulatory strategies for improving the cure rate of HBV

Over a five-year period, the objectives of the IP-cure-B project (H2020) are to conduct a proof-of-concept clinical trial, sponsored by ANRS MIE, to evaluate new immunomodulatory strategies aimed at enhancing innate immunity and reshaping the immune environment of the infected liver, with the goal of improving adaptive immunity and the response to therapeutic vaccine stimulation.

This is an exploratory, open-label, multicentre, randomised Phase II study designed to determine whether, in patients with chronic hepatitis B who are non-cirrhotic, HBeAg-negative and virologically controlled, discontinuation of NUC treatment, or discontinuation of NUC treatment following administration of SLGN, can increase the rate of HBsAg decline compared with standard treatment for chronic hepatitis B. All currently approved NUC treatments will be permitted, namely tenofovir/TDF, tenofovir/TAF and entecavir. Exploratory analyses will help determine whether changes in the liver's immune environment are responsible for the decline in HBsAg.

Participants are being recruited at several expert hepatology sites across Europe in four countries: Germany, Spain, France and Italy.

Participants are randomised to one of the following groups: "control" (Arm A), "NUC treatment discontinuation" (Arm B), or "NUC treatment discontinuation + SLGN" (Arm C). Participants in the control arm will receive NUC treatment alone throughout the trial. Participants in Arms B and C will be followed for 48 weeks after treatment discontinuation. Clinical and biological parameters will be monitored throughout the study. The safety of participants randomised to each arm will be continuously monitored, and temporary treatment discontinuation rules will be defined in the protocol so that ad hoc meetings of the Data Safety Monitoring Board (DSMB) can be convened in the event of safety concerns.