A Study of Hepalatide Combined With TAF and PEG-IFN as Finite Treatment of Chronic Hepatitis B Patients

Chronic Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05244057
• Other study ID #: L47-HB-FIN-1(New Finite)
• Status: Recruiting
• Phase: Phase 2
• Start date: August 23, 2022
• Est. completion date: August 2024

Study information

• Verified date: December 2023
• Source: Shanghai HEP Pharmaceutical Co., Ltd.
• Contact: Xiaolu Tang
• Phone: 86-21-68412368 ext 609
• Email: tangxiaolu_hep[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 all treatments and followed with further 24 weeks follow-up.

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 (24 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 76 weeks (including screening period).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Hepalatide
4.2mg, s.c., qd for 48 weeks
• Placebo of Hepalatide
s.c., qd for 48 weeks
• Tenofovir Alafenamide Tablets
25mg, p.o., qd for 48 weeks
• Pegylated Interferon alfa 2a
90ug, s.c., qw for 48 weeks

Locations

Country	Name	City	State
China	Shanghai Tong Ren Hospital	Shanghai	Shanghai

Sponsors (3)

Lead Sponsor	Collaborator
Shanghai HEP Pharmaceutical Co., Ltd.	Shanghai East Hospital, Shanghai Tong Ren Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of subjects with sustained viral response at 48 weeks off treatment	HBV DNA<20 IU/ml	96 Weeks
Primary	Proportion of subjects with negative conversion of HBsAg	Proportion of subjects with negative conversion of HBsAg treatment at 48 weeks off treatment	96 Weeks
Secondary	Number of subjects with retreatment with NAs	Number of subjects with retreatment with NAs at 48 weeks off treatment	96 Weeks
Secondary	Number of subjects with virological relapse(VR) at 48 weeks off treatment	VR: reappearance of HBV DNA > 2000 IU/ml from undetectable status	96 Weeks
Secondary	Number of subjects with clinical relapse(CR) at 48 weeks off treatment	CR: the presence of VR with the elevation of alanine transaminase (ALT) more than two times upper limit of normal (ULN)	96 Weeks
Secondary	HBsAg is down from baseline at 48 weeks off treatment	HBsAg is down from baseline log10	96 Weeks
Secondary	Number of subjects with Serological conversion of HBsAg	Number of subjects with Serological conversion of HBsAg at 48 weeks off treatment	96 Weeks
Secondary	Change in liver stiffness at 24 weeks off treatment	The findings of Liver stiffness measurement(LSM) of Fibroscan/FibroTouch at week 48 off treatment compared to baseline	96 Weeks