A Follow-up Study of Peginterferon Alfa-2b Combined With TDF in Patients With Chronic Hepatitis B

Official title

A Multicenter, Prospective, Follow-up Study to Evaluate the Long-term Benefits of Peginterferon Alpha-2b Injection Combined With TDF in Patients With Chronic Hepatitis B

Overview

Studies have shown that chronic hepatitis B patients with low levels of HBsAg after nucleos(t)ide analog therapy have a higher chance of functional cure with sequential or combined pegylated interferon therapy, with about 30-50% of patients achieving HBsAg clearance and discontinuing therapy. There are some clinical practices on the long-term benefits of discontinuing antiviral therapy, but there is a lack of evidence-based clinical studies, especially on the relapse rate, duration of relapse, and factors influencing relapse after achieving functional cure. Furthermore, there is no guideline or expert consensus on the follow-up management strategy for patients who haven't achieved functional cure but whose HBsAg levels have been substantially reduced by treatment and are at low levels. Therefore, this study is planned to enroll participants who have completed the TB1901IFN to evaluate the long-term benefit of Peginterferon in combination with tenofovir disoproxil fumarate（TDF） and relapse in patients who have achieved functional cure, for participant with low-level HBsAg at the end of treatment, peginterferon combined with tenofovir alafenamide fumarate （TAF）therapy will be administered to explore the efficacy and safety of starting treatment after a period of drug discontinuation. Participants will be divided into 3 cohorts based on functional achievement and/or HBsAg levels after completion of TB1901IFN

Interventions

• Drug Peginterferon α-2b Injection; Tenofovir Alafenamide Fumarate
  Peginterferon α-2b Injection, subcutaneous injection, once a week. Tenofovir Alafenamide Fumarate, Oral administration, once a day.

Primary outcome measures

• The incidence of Hepatocellular Carcinoma(HCC). [Time frame: 5 years after the completion of the TB1901IFN study.]
• The incidence all-cause mortality. [Time frame: 5 years after the completion of the TB1901IFN study.]
• Relapse within 5 years of discontinuation in participants who achieved functional cure. [Time frame: 5 years after the completion of the TB1901IFN study.]
• Rate of functional cure of re-initiation of combination therapy after discontinued for more than 24 weeks in participants who had a favorable outcome on prior therapy and obtained low levels of S antigen. [Time frame: After completing the 72-week combined re-treatment.]

Eligibility criteria

Inclusion criteria

• Participants who completion of the TB1901IFN study ("completion" is defined as completion of more than 80% of trial medications (including peginterferon alfa and tenofovir disoproxil fumarate), or meeting criteria for early discontinuation and completion of consolidation therapy, as well as completion of discontinuation follow-up and 24-week post-discontinuation visit);
• Voluntary enrollment, understand and sign the informed consent form.

For cohort 1 only; - Subjects who have achieved functional cure (defined as the disappearance of HBsAg at the completion of TB1901IFN, with or without the appearance of HBsAb);

For cohort 2 only:

• At the completion of TB1901IFN, the S antigen level has decreased by ≥1 log compared to the baseline, with an S antigen level of less than 100 IU/ml, or the S antigen level has decreased by ≥1.5 log compared to the baseline, with an S antigen level of less than 1500 IU/ml;
• Willing to accept the treatment of peginterferon combined with TAF;

For cohort 3 only:

\- Participants who have not achieved functional cure upon completion of TB1901IFN (defined as HBsAg ≥ 0.05 IU/ml)；

Exclusion criteria

\- Suspected or confirmed HCC patients.

For Cohort 2 only:

• Suspected or confirmed liver cirrhosis.
• Pregnant, breastfeeding women, or those who plan to conceive during the combined medication treatment period.
• Evidence of acute severe liver injury: e.g. ALT > 10 times of the upper limit of normal (ULN), or a significant increase in ALT accompanied by a significant increase in bilirubin;
• Evidence of decompensated liver disease: serum total bilirubin > 2ULN, serum albumin < 35 g/L, prothrombin time extended by more than 3 seconds beyond ULN, prothrombin activity < 60%; or a history of decompensated liver cirrhosis;
• Kidney disease: acute or chronic nephritis, renal insufficiency, nephrotic syndrome, etc., or serum creatinine > 1ULN;
• Neutrophil count < 1.5×10\^9/L, platelet count < 90×10\^9/L;
• Severe retinopathy or other severe ophthalmic diseases;
• Other conditions deemed by the investigator to be unsuitable for participation in the cohort 2.

For cohort 3 only:

\- Participants who plan to enter Cohort 2.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Factorial

Masking

Open label

Primary purpose

Treatment

Study locations

China · 30 centers

• Peking University First Hospital — Beijing
• Beijing Youan Hospital, Capital Medical University — Beijing
• The fifth medical center of PLA General Hospital — Beijing
• The Second Xiangya Hospital of Central South University — Changsha
• Xiangya Hospital Central South University — Changsha
• Public Health Clinical Center of Chengdu — Chengdu
• Sichuan Provincial People's Hospital — Chengdu
• Mengchao Hepatobiliary Hosipital of Fujian Medical University — Fuzhou
• … and 22 more centers

Identifiers

NCT: NCT06707922 · TB2111IFN

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗