Phase III Clinical Trial of Hepalatide in Patients With Chronic Hepatitis D

Official title

Double-blinded Placebo-controlled Multi-center Phase III Clinical Trial of Hepalatide in Patients With Chronic Hepatitis D

Overview

This study adopts a multicenter, randomized, double-blind, placebo-parallel controlled design to evaluate the efficacy and safety of L47 in the treatment of chronic hepatitis D. A total of 150 subjects are planned to be enrolled. After passing the screening, they will be randomly assigned to the L47 group or the placebo group at a ratio of 2:1, with liver cirrhosis and subjects' regional distribution as stratification factors. The two groups will receive hepratide (2.1 mg/day) or placebo, respectively. Upon completion of the 48-week double-blind treatment phase, all subjects in each group can enter the open-label treatment follow-up phase, where they may voluntarily choose to receive L47 (2.1 mg/day) treatment or undergo follow-up observation only, until week 144. Subjects who discontinue treatment prematurely during the trial may also enter the open-label treatment follow-up phase. An interim analysis will be conducted after the subjects complete 24 weeks of trial treatment, with the comprehensive response rate at week 24 as the primary endpoint. The analysis will be performed by an independent statistical team. And the interim analysis results will be reviewed by the Independent Data Monitoring Committee (IDMC) . All subjects will complete the 48-week double-blind clinical trial. Throughout the entire study period, the safety of subjects will be closely monitored and evaluated, including the monitoring of adverse events (AEs) and other safety indicators.

Interventions

• Drug Hepalatide 2.1mg
  Continuous treatment with hepalatide 2.1mg sc, qd, for 48 weeks
• Drug Placebo of Hepalatide
  Continuous treatment with placebo of hepalatide for 48 weeks

Primary outcome measures

• Proportion of subjects who achieved response [Time frame: 48 weeks of treatment]

Secondary outcome measures (11)

• Proportion of subjects with a ≥ 2 log₁₀ decrease in HDV RNA from baseline [Time frame: 48 weeks of treatment]
• Proportion of subjects with a ≥ 2 log₁₀ decrease in HDV RNA from baseline and normalized ALT [Time frame: Continuous treatment for 48 weeks]
• Proportion of subjects with HDV RNA below the limit of detection (LOD) [Time frame: Continuous treatment for 48 weeks]
• Changes in HDV RNA relative to baseline [Time frame: Continuous treatment for 48 weeks]
• Proportion of subjects with normalized ALT [Time frame: Continuous treatment for 48 weeks]
• Changes in ALT relative to baseline [Time frame: Continuous treatment for 48 weeks]
• Changes in HBV-related parameters (HBV DNA, HBeAg, qHBsAg, etc.) [Time frame: Continuous treatment for 48 weeks]
• Changes in histological response of the liver [Time frame: Continuous treatment for 48 weeks]
• Change in Model for End-Stage Liver Disease (MELD) score [Time frame: Continuous treatment for 48 weeks]
• Change in Child-Turcotte-Pugh score [Time frame: Continuous treatment for 48 weeks]
• Occurrence of liver-related endpoint events [Time frame: continuous treatment for 48 weeks]

Eligibility criteria

Inclusion criteria

• Positive HBsAg or HBV DNA for at least 6 months (diagnosed as chronic hepatitis B), with stable nucleos(t)ide analogue (NA) treatment for ≥3 months prior to screening and documented HBV DNA suppression;
• Positive anti-HDV antibody (IgG and/or IgM) and at least two quantifiable HDV RNA measurements ≥3 months apart, with quantifiable HDV RNA at enrollment;
• 1×ULN< ALT<10×ULN；
• No plan for pregnancy within 2 years; female subjects must not be pregnant or lactating, and all subjects must agree to use effective contraception during treatment and for 3 months after the last dose;
• No participation in other clinical trials within 3 months prior to screening;
• Good compliance with the study protocol;
• Ability to understand and willingness to sign the informed consent form (ICF).

Exclusion criteria

• Child-Pugh class C or Child-Pugh score ≥10;
• Subjects with any of the following conditions:

• History of severe decompensated liver disease, including moderate to severe ascites (grade 2 or 3), hepatic encephalopathy, gastrointestinal variceal bleeding, hepatorenal syndrome, etc., with an expected survival of less than 2 years;
• History of severe cardiac disease (including unstable or uncontrolled heart disease within the past 6 months, or New York Heart Association \[NYHA\] functional class III-IV);
• Uncontrolled epilepsy, severe psychiatric disorders, or a history of severe psychiatric disorders;
• History of organ transplantation;
• Diabetes mellitus or hypertension that is not adequately controlled;
• Presence of autoimmune diseases, immune-related extrahepatic manifestations (including vasculitis, purpura, polyarteritis nodosa, peripheral neuropathy, and glomerulonephritis), thyroid diseases, malignancies, or receipt of immunosuppressive therapy;
• Presence of serious underlying diseases such as severe infection, heart failure, chronic obstructive pulmonary disease, or other serious diseases;
• History of alcohol abuse or drug addiction.
• Total bilirubin > 51 μmol/L, or serum albumin < 28 g/L, or prothrombin time prolonged by > 6 seconds;
• Creatinine clearance<60mL/min；
• Co-infection with hepatitis A, C, or E virus, or HIV infection;
• Use of interferon within 3 months prior to screening;
• Positive pregnancy test in female subjects;
• Abnormal hematology results: white blood cell count (WBC) < 3×10\^9/L, neutrophil count 1.5×10\^9/L, or platelet count 60×10\^9/L；
• Current use of prohibited medications that cannot be discontinued;
• Use of L47 or Myrcludex B within 3 months prior to screening;
• Subjects receiving standardized nucleos(t)ide analogue (NA) therapy with a treatment duration of less than 12 weeks;
• Other significant abnormalities in laboratory tests or auxiliary examinations that, in the opinion of the investigator, make the subject unsuitable for participation in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• First Hospital of Jilin University — Changchun

Identifiers

NCT: NCT07309380 · L47-HD-II/III-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗