Table 3.

Consensus Among Stakeholders for Finite Therapy of Chronic Hepatitis B Investigational Studies

Area of Interest	Consensus
Design of studies	Designing new finite duration therapeutic regimens to achieve functional cure is complex owing to the differing MOAs and heterogeneity based on patient characteristics; early patient input will enhance acceptability of new drugs and trial design; combining new regimens from different industry partners is encouraged.
Patient selection	Initial studies of finite and curative investigational therapies should focus on enrollment of patients without cirrhosis and with minimal fibrosis for the safety of trial participants, especially when finite treatments are assessed; special populations should be added after safety and efficacy is established.
Outcomes	Functional cure is defined as HBsAg loss, with or without detection of antibody to HBsAg (anti-HBs >10 IU/mL), and HBV DNA below the LLOQ sustained for ≥24 wk off all treatment; partial cure is defined as HBsAg positivity, and HBV DNA below the LLOQ sustained for ≥24 wk off all treatment and should be included as a secondary end point.
Biomarkers	New treatment regimens should achieve on-treatment suppressed HBV DNA and RNA and significant reductions in HBsAg (ideally HBsAg negativity) to increase the chances of achieving functional cure and to minimize risks of virologic and clinical relapse; HBsAg level at EOT is the most promising biomarker associated with lower chance of disease relapse and higher likelihood of HBsAg loss after stopping therapy; EOT HBsAg <100 IU/mL, HBcrAg <4 log10 U/mL, and HBV RNA negativity may improve accuracy in identifying patients who could benefit from stopping treatment.
Predefined stopping criteria	Predefined stopping criteria should include low or negative HBsAg, negative HBV DNA, and normal or slightly elevated ALT.
Predefined retreatment criteria	The threshold for retreating study participant needs to be carefully predefined in the protocol based on latest data to allow adequate time to see an off-treatment response while ensuring patient safety; off-treatment monitoring must be frequent (every 2–4 wk), with rapid turnaround of liver and virologic (HBV DNA, quantitative HBsAg) tests.
Duration of investigational therapies	The duration and complexity of any treatment regimens should be acceptable to the patient population (duration ideally ≤48 wk).
Follow-up after stopping therapy	Patients should be followed up for at least 48 wks; long-term follow-up studies are recommended to assess durability or response, additional HBsAg loss, and late relapse.

Abbreviations: ALT, alanine aminotransferase; anti-HBs, antibody to HBsAg; EOT, end of treatment; HBsAg, hepatitis B surface antigen; LLOQ, lower limit of quantitation; MOAs, mechanisms of action.