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

Not Applicable

• Conditions: Chronic Hepatitis B
• Interventions: Drug: Peginterferon α-2b Injection; Tenofovir Alafenamide Fumarate

• Registration Number: NCT06707922
• Lead Sponsor: Xiamen Amoytop Biotech Co., Ltd.

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2022-03-18
• Status Verified: 2024-11
• Study First Submitted: 2024-11-24
• Study First Submitted QC: 2024-11-26
• Study First Posted: 2024-11-27
• Last Update Submitted: 2024-11-29
• Last Update Posted: 2024-12-04
• Primary Completion: 2029-05-31
• Study Completion: 2029-07-31

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 350

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)；

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Cohort 2	Peginterferon α-2b Injection; Tenofovir Alafenamide Fumarate	Participants with S antigen decrease≥1log and the S antigen level \<100IU/ml at enrollment, or who with S antigen decrease ≥1.5log and the S antigen level \<1500IU/ml after TB1901IFN treatment, will initially treated with 72-week pulse treatment of peginterferon in combination with TAF, and then followed up to 5 years.

Primary Outcome Measures

Name	Time	Method
The incidence of Hepatocellular Carcinoma(HCC).	5 years after the completion of the TB1901IFN study.
The incidence all-cause mortality.	5 years after the completion of the TB1901IFN study.
Relapse within 5 years of discontinuation in participants who achieved functional cure.	5 years after the completion of the TB1901IFN study.	Relapse was defined as the occurrence of two consecutive time, interval greater than one month, HBsAg≥0.05 IU/ml at any time during the follow-up period
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.	After completing the 72-week combined re-treatment.