A Phase II Study of Hepalatide in Subjects With Chronic Hepatitis B

Hepatitis B, Chronic Clinical Trial

Official title:

A Phase II Randomized, Double-blind, Placebo-controlled, Multi-center, Dose-effect Relationship Study of Hepalatide for Injection Combined With Pegylated Interferon in Subjects With Chronic Hepatitis B

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04426968
• Other study ID #: L47-HB-II-02
• Status: Completed
• Phase: Phase 2
• Start date: June 18, 2021
• Est. completion date: November 29, 2023

Study information

• Verified date: December 2022
• Source: Shanghai HEP Pharmaceutical Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Phase II Randomized, Double-blind, Placebo-controlled, Multi-center, Dose-effect Relationship Study of Hepalatide for Injection Combined with Pegylated Interferon in Subjects with Chronic Hepatitis B

Description:

The study is a 4-arm parallel design, randomized, double-blind, placebo-controlled, multicenter, dose-effect relationship, phase II clinical trial. The study is designed to assess efficacy and safety of 3 Doses of hepalatide in Combination with Pegylated Interferon Compared to Pegylated Interferon Alone in patients with Chronic Hepatitis B .Subjects will be randomly assigned to the 2.1mg, 4.2mg, and 6.3mg dose groups , 32 subjects in each group . The subjects in each dose group will be randomly and double-blindly administered the corresponding dose of trial drug or placebo in a ratio of 3:1. The subjects in each dose group who received placebo treatment combine as the placebo group. All subjects will receive Pegylated Interferon treatment for 28 weeks as the basic treatment,trial drug or placebo treatment for 24 weeks continuously , followed by a safety follow-up for 4 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: November 29, 2023
• Est. primary completion date: November 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Age from 18 to 60 years inclusively at the time of signing Informed Consent Form.

2. HBsAg or/and HBV DNA Positive for at least 6 months before Screening.

3. Subjects did not receive interferon treatment and did not receive nucleotide/nucleoside analogue within 6 months

4. HBeAg positive or negative

5. HBV DNA=20,000 IU/ml (HBeAg positive) or HBV DNA=2,000 IU/ml (HBeAg negative)

6. 2×ULN =ALT=10×ULN

7. Serum total bilirubin<2×ULN

8. Subjects had no history of decompensated liver disease(Ascites, jaundice, hepatic encephalopathy, varicose hemorrhage), serious heart disease (including unstable or uncontrolled heart disease within 6 months),serious mental illness (especially depression),organ transplantation .subjects have no uncontrolled epilepsy, mental illness, diabetes and hypertension,no autoimmune disease, immune related extrahepatic manifestations (vasculitis, purpura, nodular arteritis, peripheral neuropathy and glomerulonephritis), thyroid disease, malignant tumor, immunosuppressive therapy; no basic diseases and other serious diseases such as serious infection, retinal disease, heart failure and chronic obstructive pulmonary disease; no alcohol and drug abuse.

9. Subjects must agree to use a highly effective contraception for 2 years , female subjects are not pregnant or breastfeeding

10. Subjects did not donate blood or as clinical trial subjects within 3 months before screening

11. Subjects have good compliance with the protocol

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

Exclusion Criteria:

1. Decompensated liver disease: direct bilirubin > 1.2 × ULN,

2. Prothrombin time > 1.2 × ULN, serum albumin < 35 g / L

3. Severe liver fibrosis or cirrhosis: METAVIR score of liver biopsy is 4 points; or or Child-Pugh score> 7

4. Hemocytopenia: neutrophil < 1 × 10^9 / L, platelet < 50 × 10^9 / L, hemoglobin < 100g / L (female) or hemoglobin < 110g / L (male) points

5. HAV,HCV,HDV,HEV or HIV infection

6. Pegylated interferon therapy is contraindicated

7. Allergic to interferon, Such as severe depression, epilepsy, autoimmune diseases, uncontrolled thyroid dysfunction and so on

8. severe retinopathy or eye disease(Eye diseases due to high blood pressure or diabetes, CMV retinitis, macular degeneration)

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

10. Hamilton Depression Scale (HAMD, 17 items) score > 17 points

11. Female subjects pregnancy test positive

12. Other laboratories or auxiliary examinations are obviously abnormal

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Drug:
• Hepalatide 2.1mg
2.1 mg/day subcutaneously (s.c.) for 24 week
• Hepalatide 4.2mg
4.2mg/day subcutaneously (s.c.) for 24 week
• Hepalatide 6.3mg
6.3mg/day subcutaneously (s.c.) for 24 week
• placebo 2.1mg
2.1 mg/day subcutaneously (s.c.) for 24 week
• placebo 4.2mg
4.2 mg/day subcutaneously (s.c.) for 24 week
• placebo 6.3mg
6.3 mg/day subcutaneously (s.c.) for 24 week
• Pegylated Interferon
180 ug/week subcutaneously (s.c.) for 28 week

Locations

Country	Name	City	State
China	The fifth medical center of PLA	Beijing	Beijing
China	Jilin Hepatobiliary Disease Hospital	Changchun
China	The first hospital of Jilin University	Changchun
China	Chizhou People's Hospital	Chizhou
China	The First Hospital Affiliated to the Army Medical University	Chongqing
China	The First Affiliated Hospital of Nanchang University	Nanchang
China	The Second Hospital of Nanjing	Nanjing
China	Qingyuan People's Hospital	Qingyuan
China	Shanghai Tongren Hospital	Shanghai
China	The Sixth People's Hospital of Shenyang	Shenyang
China	Henan Provincial People's Hospital	Zhengzhou
China	Henan Provincial Infectious Disease Hospital	Zhenzhou

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai HEP Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Virological suppression	HBV DNA <2,000 IU/ml	24weeks
Other	No response	HBsAg >20,000 IU/ml and HBV DNA lower than baseline <2log10 IU/ml	24weeks
Other	Partial virological response	HBV DNA >20 IU/ml and =2log10 IU/ml lower than baseline	24weeks
Other	HBsAg is down from baseline	HBsAg is down from baseline log10	24weeks
Other	HBeAg turned negative	HBeAg <0.05 index	24weeks
Other	HBeAg is down from baseline	HBeAg is down from baseline log10	24weeks
Other	ALT recurrence	ALT=1.25×ULN	24weeks
Other	Histological response	Liver tissue inflammatory necrosis score reduced by =2 points with no increased liver fibrosis score; liver fibrosis score reduced by =1 point	24weeks
Primary	initial virological response	HBV DNA<20 IU/ml	24weeks
Secondary	HBV DNA down from baseline	HBV DNA down from baseline log10	24weeks