Clinical trial NCT05244057: A Study of Hepalatide Combined With TAF and PEG-IFN as Finite Treatment of Chronic Hepatitis B Patients
Official title: A Phase II of Randomized, Double-blind, Placebo-controlled, Multi-center Study of Hepalatide for Injection Combined With Pegylated Interferon and TAF as Finite Treatment in Chronic Hepatitis B Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Keywords: hepalatide, Hepatitis B，finite treatment,
Lead sponsor: Shanghai HEP Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Tong Ren Hospital
name: Shanghai East Hospital
First posted: 2022-02-17
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is designed to assess efficacy of a finitie treatment in Chronic Hepatitis B patients who had stable treatment of NAs for ≧ 2 years， which is compared hepalatide in combination with Pegylated Interferon + TAF with Pegylated Interferon +TAF. Subjects will be randomly assigned to the hepalatide or placebo groups , 15 subjects in each group . Subjects will receive hepalatide+Pegylated Interferon +TAF treatment for 48 weeks or placebo +PegylatedInterferon +TAF treatment for 48 weeks , Then, stopping hepalatide and Pegylate Interferon treatments and followed with further 8 weeks follow-up.

Detailed description: Hepalatide is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection. The aim of this study is to assess efficacy of a finitie treantment , that combination regimen of hepalatide+half dose Pegylated interferon + TAF , as measured by the primary efficacy endpoint. This study will be conducted in 3 periods: Screening Period (4weeks), Treatment Period (48 weeks) and Follow-up (FU) Period (8 weeks). Safety assessments will include adverse events (AEs), serious AEs, clinical safety laboratory tests, electrocardiograms (ECGs), vital signs, ophthalmologic examinations and physical examinations. Total duration of individual participation will be up to 60 weeks (including screening period).

Eligibility criteria: Inclusion Criteria:

* 1. HBsAg or/and HBV DNA Positive for at least 6 months

  2. HBeAg negative

  3. Received NAs stabilization therapy for at least 2 years

  4. ALT≤ 2×ULN

  5. HBV DNA\< LLQD(lower limit of quantitative detection) in Screening

  6. Serum total bilirubin\<2×ULN

  7. no childbirth plan within 2 years and agree to take effective contraceptive measures throughout the treatment period and within 3 months after the last dose, and that the woman is not pregnant or breastfeeding.

  8. have not participant in another clinical trial within 3 months before screening

  9. Subjects have good compliance with the protocol

  10. Subjects understood and agreed to sign the informed consent form.

Exclusion Criteria:

* 1. Contraindications of Peginterferon such as depressive disorder, epilepsy, autoimmune diseases, uncontrolled thyroid dysfunction, etc

  2. Subjects with cirrhosis, e.g., definite cirrhosis on imaging such as abdominal ultrasound and CT; liver biopsy with Metavir fibrosis score = 4; clinical diagnosis of cirrhosis by the investigator.

  3. Decompensated liver disease

  4. Child-Pugh score of B-C or over 6 points.

  5. Subjects with any of the following circumstances
* History of decompensated liver disease
* History of serious heart disease (including unstable or uncontrolled heart disease within 6 months)
* Uncontrolled seizures, severe psychiatric disorders, or a history of psychiatric disorders
* with history of organ transplantation
* with poorly controlled diabetes and hypertension
* with autoimmune diseases, immune-related extrahepatic manifestations, thyroid disease, malignant tumors, or in immunosuppressive therapy
* underlying diseases such as malignant tumor, severe infection, heart failure and chronic obstructive pulmonary disease and other serious diseases.
* with history of alcohol or drug abuse

  6. Creatinine clearance \<60 mL/min.

  7. HAV, HCV, HDV, HEV or HIV co-infection

  8. Subjects who must be treated with Nucleosides (acids) other than TAF during treatment period

  9. Subjects who used interferon in the 6 months prior to the screening period

  10. Positive for anti-HBV Pre-S1 antibody.

  11. Hemocytopenia: White blood cells \< 3 × 10\^9 / L, neutrophil \< 1.5 × 10\^9 / L, platelet \< 60 × 10\^9 / L,

  12. Female subjects pregnancy test positive

  13. known to be allergic to the investigational drug or the underlying treatment drug

  14. Other laboratories or auxiliary examinations are obviously abnormal

Primary outcomes:
measure: Proportion of subjects with negative conversion of HBsAg
timeFrame: 56 Weeks
Secondary outcomes:
measure: Number of subjects with virological relapse(VR) at 8 weeks off treatment
timeFrame: 56 Weeks
measure: Number of subjects with clinical relapse(CR) at 8 weeks off treatment
timeFrame: 56 Weeks
measure: HBsAg is down from baseline at 8 weeks off treatment
timeFrame: 56 Weeks
measure: Number of subjects with Serological conversion of HBsAg
timeFrame: 56 Weeks
measure: Change in liver stiffness at 8 weeks off treatment
timeFrame: 56 Weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Tong Ren Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Tong Ren Hospital
name: Qin Zhang
role: PRINCIPAL_INVESTIGATOR
References: