Study of Hepalatide in Chronic Hepatitis D(CHD) Patients

Study Overview
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Brief Summary
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A phase 2a clinical Study of Hepalatide for Injection in Subjects with Chronic Hepatitis D

Detailed Description
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This is a four-arm parallel-group, randomized, placebo-controlled, double-blind, multicenter Phase IIa clinical trial. The CHD subjects who meet the eligibility criteria will be randomly assigned 1:1:1:1 to receive either the placebo or investigational drug (2.1 mg, 4.2 mg, or 6.3 mg), with 6 subjects per group . The placebo or the corresponding dose of the investigational drug will be given for 4 consecutive weeks, followed by a 4-week follow-up period. Subjects will be given entecavir for the treatment of hepatitis B infection during and after the end of the trial.

Official Title
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Double-blinded, Placebo-controlled, Munticenter, Phase IIa Clinical Trial of Hepalatide in Patients With Chronic Hepatitis D

Conditions
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Chronic Hepatitis D Infection

Intervention / Treatment
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* Drug: Hepalatide
* Drug: Hepalatide Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18-65 years old (both inclusive); HBsAg (+) and/or HBV DNA (+) for at least 6 months (clinically diagnosed as chronic hepatitis B); HDV-antibody (IgG/IgM) (+) and HDV RNA (+); 1×ULN <ALT<10×ULN； Patients with hepatitis B eligible to receive treatment with NAs according to current guidelines for the diagnosis and treatment of hepatitis B; Patients who do not plan a pregnancy within two years (women who are not pregnant or lactating) and agree to take effective contraceptive measures throughout the treatment period and within 3 months after the last dose; Patients who did not participate in any other clinical trials within 3 months; Patients with good compliance with the study protocol; Patients who understand and agree to sign an informed consent form. Exclusion Criteria: Decompensated liver disease: Direct bilirubin > 1.2× ULN, prothrombin time > 1.2× ULN, and serum albumin < 35 g/L; Patients with abnormal results of routine hematology test: White blood cell count (WBC) < 3×109/L, neutrophil count < 1.5×109/L and platelet count < 60×109/L; Severely decompensated hepatic fiborosis or decompensated cirrhosis: Definitely diagnosed decompensated cirrhosis by imaging examinations such as a Color Doppler ultrasound and CT of the abdomen or clinically diagnosed decompensated cirrhosis by the investigator, or a Metavir fibrosis score of 4 on a liver biopsy sample, or a Child-Pugh score > 7 for liver function assessment; Patients who have any of the following conditions: A history of decompensated liver disease (ascites, jaundice, hepatic encephalopathy, variceal bleeding); A history of serious cardiovascular disease (including unstable or uncontrolled cardiovascular disease within 6 months); Serious mental illness or a history of serious mental illness; A history of organ transplantation; Uncontrolled epilepsy, mental illness, or poorly controlled diabetes or hypertension; Autoimmune disease, immune-related extrahepatic manifestations (vasculitis, purpura, arteritis nodosa, peripheral neuropathy, and glomerulonephritis), thyroid disease, malignant tumor, and receiving immunosuppressive therapy; Underlying diseases such as severe infection, heart failure, chronic obstructive pulmonary disease, and other severe diseases; A history of alcohol or drug abuse. Creatinine clearance < 60 mL/min; HAV/HCV/HEV/HIV co-infection; Resistance to or poor response to Entecavir; An allergic reaction to Entecavir; Patients who have used interferon within 3 months before the screening period; Previously received L47 or Bulevirtide; Women who have a positive pregnancy test; Patients who have other significantly abnormal results of laboratory or auxiliary tests and are unsuitable for this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hepalatide 2.1mg<br>2.1 mg/day subcutaneously (s.c.) for 4 week | Drug: Hepalatide<br>* Either the placebo or hepalatide (2.1 mg, 4.2 mg, or 6.3 mg) will be given for 4 consecutive weeks. s.c., once daily.<br>* Other names: L47;|
| Experimental: Hepalatide 4.2mg<br>4.2 mg/day subcutaneously (s.c.) for 4 week | Drug: Hepalatide<br>* Either the placebo or hepalatide (2.1 mg, 4.2 mg, or 6.3 mg) will be given for 4 consecutive weeks. s.c., once daily.<br>* Other names: L47;|
| Experimental: Hepalatide 6.3mg<br>6.3 mg/day subcutaneously (s.c.) for 4 week | Drug: Hepalatide<br>* Either the placebo or hepalatide (2.1 mg, 4.2 mg, or 6.3 mg) will be given for 4 consecutive weeks. s.c., once daily.<br>* Other names: L47;|
| Placebo Comparator: Placebo 2.1mg/4.2mg/6.3mg<br>Placebo 2.1 mg/4.2mg/6.3mg, once a day subcutaneously (s.c.) for 4 week | Drug: Hepalatide Placebo<br>* Either the placebo or hepalatide (2.1 mg, 4.2 mg, or 6.3 mg) will be given for 4 consecutive weeks. s.c., once daily.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hepatitis D Virus(HDV) RNA level | HDV RNA level at week4 | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Alanine transaminase(ALT) from baseline | Changes in ALT values at Week 4 compared to baseline | Week 4 | 
| Change in HDV RNA from baseline | Changes in HDV RNA levels at Week 4 compared to baseline | Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic hepatitis D, hepalatide, hepatitis D virus