Chronic Hepatitis B
Conditions
Keywords
hepalatide, Hepatitis B，finite 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).
Interventions
DRUGHepalatide
6.3mg, s.c., qd for 48 weeks
s.c., qd for 48 weeks
25mg, p.o., qd for 48 weeks
90ug, s.c., qw for 48 weeks
Sponsors
Shanghai Tong Ren Hospital
Shanghai East Hospital
Shanghai HEP Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of subjects with negative conversion of HBsAg | 56 Weeks | Proportion of subjects with negative conversion of HBsAg treatment at 8 weeks off treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with virological relapse(VR) at 8 weeks off treatment | 56 Weeks | VR: reappearance of HBV DNA \> 2000 IU/ml from undetectable status |
| Number of subjects with clinical relapse(CR) at 8 weeks off treatment | 56 Weeks | CR: the presence of VR with the elevation of alanine transaminase (ALT) more than two times upper limit of normal (ULN) |
| HBsAg is down from baseline at 8 weeks off treatment | 56 Weeks | HBsAg is down from baseline log10 |
| Number of subjects with Serological conversion of HBsAg | 56 Weeks | Number of subjects with Serological conversion of HBsAg at 8 weeks off treatment |
| Change in liver stiffness at 8 weeks off treatment | 56 Weeks | The findings of Liver stiffness measurement(LSM) of Fibroscan/FibroTouch at week 8 off treatment compared to baseline |
Countries
China
Outcome results
None listed