Evaluation of Ethnicity's Impact on Viral Outcomes Post-Cessation of Tenofovir Alafenamide and Entecavir in HBeAg-Negative Chronic Hepatitis B Patients

The primary objective of this study is to investigate the contribution of **ethnicity** to the off-treatment viral outcomes following controlled nucleos(t)ide analogue cessation in patients with HBeAg negative **chronic hepatitis B infection**. This is clinically relevant as it may provide insights into personalized treatment strategies based on ethnic differences, potentially improving patient outcomes and optimizing treatment protocols.

Secondary objectives include:

• Comparing the occurrence of HBsAg loss at week 72 after treatment cessation and the time to achieve HBsAg loss between Caucasian and non-Caucasian patients.
• Estimating the cost-effectiveness of treatment cessation and making long-term projections.

The clinical trial focuses on individuals diagnosed with **chronic hepatitis B infection**, specifically those who are HBeAg negative at the start of nucleos(t)ide analogue treatment. The study population includes both male and female participants, aged between 18 and 75 years. Participants are required to have been under continuous nucleos(t)ide analogue treatment, with HBV DNA levels below the local limit of quantification for at least 36 months at cessation or ≤ 2log IU/mL for at least 48 months at cessation. Additionally, participants must have ALT levels ≤ 2x the upper limit of normal on two sequential measurements at least six months apart, one of which must be at screening. The trial does not include vulnerable populations. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is designed to evaluate the impact of ethnicity on viral outcomes following the cessation of nucleos(t)ide analogue treatment in patients with **chronic hepatitis B** infection. This is a phase 4, randomized, double-blind, controlled trial. The trial is expected to commence recruitment on October 10, 2024, and conclude by December 31, 2025. The study will involve a series of visits, starting with an inclusion visit where participants will be screened based on specific criteria, including age (18-75 years), confirmed chronic hepatitis B status, and specific treatment history. Participants must have been under continuous nucleos(t)ide analogue treatment with **HBV DNA** levels below the local limit of quantification for at least 36 months or ≤2log IU/mL for at least 48 months, and **ALT** levels ≤2x Upper Limit Normal on two sequential measurements.

Following the inclusion visit, participants will undergo regular follow-up visits to monitor their health status and treatment response. The primary endpoint is the occurrence of viral control, defined as HBV DNA ≤2000 IU/mL and ALT ≤2xULN, 72 weeks after treatment cessation. The secondary endpoint is the loss of **HBsAg** at week 72 post-treatment cessation. The trial will involve oral administration of the investigational products, including Vemlidy, Tenofovir disoproxil, and Entecavir, with a maximum treatment period of 240 days. Participants are expected to be involved in the study for the entire duration unless they meet conditions for early termination, such as adverse reactions or withdrawal of consent. The study aims to provide valuable insights into the management of chronic hepatitis B, particularly in relation to ethnic differences in treatment outcomes.

The clinical trial involves the administration of several **experimental medications** for the treatment of chronic hepatitis B infections. The first medication is Vemlidy, which contains the active substance **tenofovir alafenamide**. It is provided in the form of film-coated tablets, with each tablet containing 25 mg of the active ingredient. The medication is administered orally, with a maximum daily dose of 25 mg. The treatment period can extend up to 240 days.

Another medication used in the trial is Tenofovir disoproxil Viatris, which contains **tenofovir disoproxil** as the active substance. This medication is also available as film-coated tablets, each containing 245 mg of the active ingredient. The oral administration of this medication allows for a maximum daily dose of 245 mg, with a treatment duration of up to 240 days.

Baraclude, containing the active substance **entecavir**, is also part of the trial. It is available in two dosages: 1 mg and 0.5 mg film-coated tablets. The maximum daily dose for Baraclude is 1 mg, administered orally, with a treatment period of up to 240 days.

Entecavir Krka is another formulation of **entecavir** used in the trial, available in 1 mg and 0.5 mg film-coated tablets. The administration is oral, with a maximum daily dose of 1 mg, and the treatment can last up to 240 days.

Viread, another formulation containing **tenofovir disoproxil**, is included in the trial. It is provided as 245 mg film-coated tablets, with oral administration. The maximum daily dose is 245 mg, and the treatment period is up to 240 days.

Throughout the trial, participant compliance with the dosing schedule is monitored to ensure adherence to the prescribed treatment regimen. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the trial data provided.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the occurrence of viral control, defined as **HBV DNA** ≤2000 IU/mL and **ALT** ≤2xULN, measured 72 weeks after treatment cessation. The secondary endpoint is the loss of **HBsAg** at week 72 following treatment cessation. These endpoints will be evaluated to determine the effectiveness of the treatment regimen in patients with chronic hepatitis B infection.