Clinical trial NCT06707922: 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
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Chronic Hepatitis B
Keywords: Peginterferon Alfa
Tenofovir Disoproxil Fumarate
Relapse
Retreatment
Lead sponsor: Xiamen Amoytop Biotech Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Peking University First Hospital
First posted: 2024-11-27
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: The incidence of Hepatocellular Carcinoma(HCC).
timeFrame: 5 years after the completion of the TB1901IFN study.
measure: The incidence all-cause mortality.
timeFrame: 5 years after the completion of the TB1901IFN study.
measure: Relapse within 5 years of discontinuation in participants who achieved functional cure.
timeFrame: 5 years after the completion of the TB1901IFN study.
measure: 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.
timeFrame: After completing the 72-week combined re-treatment.
Secondary outcomes:
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Beijing Youan Hospital, Capital Medical University
city: Beijing
country: China
facility: The fifth medical center of PLA General Hospital
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
city: Changsha
country: China
facility: Xiangya Hospital Central South University
city: Chengdu
country: China
facility: Public Health Clinical Center of Chengdu
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
city: Fuzhou
country: China
facility: Mengchao Hepatobiliary Hosipital of Fujian Medical University
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
city: Guangzhou
country: China
facility: Guangzhou Eighth People's Hospital
city: Guanzhou
country: China
facility: The Third Affiliated Hospital,SUN YAT-SEN University
city: Harbin
country: China
facility: The Fourth Affiliated Hospital of Harbin Medical University
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
city: Shanghai
country: China
facility: Huashan Hospital ,Fudan University
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
city: Shenyang
country: China
facility: The Sixth People's Hospital of Shenyang
city: Shenzhen
country: China
facility: Peiking University Shenzhen Hospital
city: Shenzhen
country: China
facility: The Third People's Hospital of shenzhen
city: Taiyuan
country: China
facility: The First Hospital of Shanxi Medical University
city: Tianjin
country: China
facility: First Teaching Hospital of Tianjin University of Traditional Chinese Medicine
city: Tianjin
country: China
facility: Tianjin Third Central Hospital
city: Urumqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
city: Urumqi
country: China
facility: Traditional Chinese Medical hospital of Xinjiang Uygur Autonomous Region
city: Wuhan
country: China
facility: Tongji Hospital,Tongji Medical College Huazhong University of Science and Technology
city: Xi'an
country: China
facility: Tangdu Hospital,Air Force Medical University
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
city: Xiamen
country: China
facility: The First Affiliated Hospital of Xiamen University
city: Xiamen
country: China
facility: Xiamen Hospital of Traditional Chinese Medicine
city: Yanji
country: China
facility: Yanbian University Hospital/Yanbian Hospital
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
Study officials:
affiliation: Peking University First Hospital
name: Guiqiang Wang, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: