A Study of TAF in Combination With PEG-IFN and Hepalatide in Subjects With Chronic Hepatitis B

Hepatitis B, Chronic Clinical Trial

Official title:

A Phase II Randomized, Double-blind, Placebo-controlled, Multi-center Study of Finite Therapy of TAF in Combination With PEG-IFN and Hepalatide in Subjects With Chronic Hepatitis B

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05133856
• Other study ID #: L47-HB-FIN-1
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 2021
• Est. completion date: June 2024

Study information

• Verified date: November 2021
• Source: Shanghai HEP Pharmaceatical Co., Ltd.
• Contact: Fei Cai
• Phone: 86-21-68412368
• Email: caifei_hep[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is designed to assess efficacy of hepalatide in Combination with Pegylated Interferon and TAF compared to Pegylated Interferon in Combination with TAF in patients with Chronic Hepatitis B .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 +Pegylated Interferon +TAF treatment for 48 weeks , followed by a safety follow-up for 24 weeks.

Description:

Hepalatide is a liver-targeted antiviral therapeutic for subcutaneous injection designed to treat chronic hepatitis B virus (HBV) infection. Pegylated interferon and TAF are approved drugs for the treatment of chronic HBV infection . The primary hypothesis of this study is that combination regimen of hepalatide+NA+Pegylated interferon is more efficacious than NA+Pegylated interferon treatment , 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: Not yet recruiting
• Enrollment: 30
• Est. completion date: June 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• 1. 18 years = age = 60 years, both sexes.

2. HBsAg (+) or HBV DNA (+) for ? 6 months

3. HBeAg(-)

4. on stable treatment for NAs for ? 2 years.

5. HBV DNA <LLQD (lower limit of quantitative detection) at screening.

6. ULN<ALT<10×ULN.

7. total serum bilirubin <2×ULN.

8. 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.

9. have not participant in another clinical trial within 3 months

10. have good compliance with the study protocol.

11. the subject understands and agrees to sign the informed consent form

Exclusion Criteria:

• 1. contraindications to pegylated interferon therapy, such as major depression, epilepsy, autoimmune disease, uncontrolled thyroid abnormal thyroid function, etc.

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

3. decompensated liver disease: PT > 1.2 x ULN, serum albumin < 35 g/L

4. liver function Child-Pugh grade B-C or score >6

5. any of the following.

1. history of decompensated liver disease (ascites, hepatic encephalopathy, variceal hemorrhage, hepatorenal syndrome, etc.)

2. history of severe heart disease (including unstable or uncontrolled heart disease within 6 months)

3. uncontrolled epilepsy, severe mental illness or history of severe mental illness

4. history of organ transplantation.

5. diabetes mellitus and hypertension that are not effectively controlled

6. autoimmune diseases, immune-related extrahepatic manifestations (vasculitis, purpura, nodular arteritis, peripheral neuropathy and glomerulonephritis) , thyroid disease, malignancy, and immunosuppressive therapy.

7. with underlying diseases such as malignancy, severe infections, heart failure and chronic obstructive pulmonary disease, and other serious diseases diseases.

8. History of alcohol or drug abuse.

6. creatinine clearance <60mL/min.

7. co-infected with hepatitis A, C, D or E virus, HIV infection.

8. subjects who must be treated with anti-HBV nucleoside (acid) analogs other than TAF during the treatment period.

9. subjects who have used interferon within 6 months prior to the screening

10. subjects with positive anti-HBV Pre-S1 antibody.

11. Abnormal blood tests: white blood cell count < 3×10^9 /L, neutrophil count < 1.5×10^9/L , platelets < 60×10^9 /L .

12. Positive pregnancy test in women.

13. patients who are taking drugs prohibited by the test and cannot be discontinued

14. patients with known allergy to the test drug or the underlying treatment drug

15. other laboratory or ancillary tests are clearly abnormal and unsuitable for participation in the test.

Related Conditions & MeSH terms

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

Intervention

Drug:
• hepalatide
4.2 mg, once daily, subcutaneously
• Pegylated Interferon
90 µg,once week ,subcutaneously
• TAF
25 mg,once daily, ,orally
• Placebo
4.2 mg, once daily, subcutaneously

Locations

Country	Name	City	State
China	Shanghai Tong Ren Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai HEP Pharmaceatical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained virologic response	Serum HBV DNA <20 IU/mL	week 72
Primary	HBsAg seroclearance	Hepatitis B Surface Antigen (HBsAg)<0.05index	week 72
Secondary	NA recurrence rate	Percentage of participants requiring NA re-treatment	week 72
Secondary	Virological relapse	Central laboratory test HBV DNA >2000IU/ml twice in a month after drug discontinuation	week 72
Secondary	Clinical relapse	After participants have achieved virologic response and drug discontinuation ,central laboratory test ALT>2×ULN,HBV DNA>2000IU/ml	week 72
Secondary	HBsAg reduction from baseline	Changes in hepatitis B surface antigen (HBsAg) (defined as decline in HBsAg levels) from baseline	week 72
Secondary	HBsAg serologic conversion	HBsAg serologic conversion	week 72
Secondary	Change in liver elasticity from baseline	Change in liver elasticity from baseline	week 72