A Study to Evaluate the Antiviral Activity and Safety of HH-003 in Chronic Hepatitis B Subjects With Low-level Viremia

A Multicenter, Randomized, Controlled Phase IIa Study to Evaluate the Antiviral Activity and Safety of HH-003 in Nucleos(t)Ide Analogues-treated Chronic Hepatitis B Subjects With Low-Level Viremia

This is a multicenter, randomized, controlled Phase IIa study of HH-003 to evaluate the antiviral activity and safety in nucleos(t)ide analogues-treated chronic hepatitis B subjects with low-level viremia. HH-003 is a human monoclonal antibody targeting the pre-S1 domain of the HBV large envelope protein. It blocks engagement of preS1 with sodium taurocholate co-transporting polypeptide (NTCP), the cellular receptor for HBV.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic HBV Infection
• Intervention / Treatment: Drug: Nucleoside/nucleotide reverse transcriptase inhibitors (NrtIs); Drug: HH-003 and NrtIs; Drug: HH-003, NrtIs and PEG-IFN-α

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100015
      • Beijing Ditan Hospital,Capital Medical University
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital,Capital Medical University
    • Beijing, Beijing, China, 100069
      • Beijing Youan Hospital,Capital Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Mengchao Hepatobiliary Hospital of Fujian Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
  • Henan
    • Zhengzhou, Henan, China, 450006
      • The Sixth Peoples Hospital Of Zhengzhou
  • Jilin
    • Changchun, Jilin, China, 130061
      • The First Hospital of Jilin University
  • Shandong
    • Jinan, Shandong, China, 250102
      • Shandong Public Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent form;
• Male or female aged from 18 to 60 years (inclusively);
• 18 kg/m^2≤BMI≤30 kg/m^2, body weight≥50 kg for men and ≥45 kg for women;
• Subjects who have chronic HBV infection greater than or equal to 6 months at screening;
• 10 IU/mL≤HBsAg≤3000 IU/mL; HBV DNA≤2000 IU/mL; ALT≤3×ULN;
• Subjects who have been on nucleoside reverse transcriptase inhibitors therapy for more than 1 year prior to screening.

Exclusion Criteria:

• Females who are pregnant or lactating at screening;
• History of alcoholic liver disease, moderate fatty liver, autoimmune liver disease, other hereditary liver disease, drug-induced liver disease or other clinically significant chronic liver disease induced by non-HBV infection;
• History of cirrhosis at any time prior to or at time of screening, or having progressive liver fibrosis at screening ;
• History or evidence of hepatocellular carcinoma at any time prior to or at time of screening;
• Exclusionary laboratory results at screening: total bilirubin >2xULN or direct bilirubin >1.5xULN，hemoglobin <120 g/L for males or <110 g/L ro females，platelets count<100,000/mm^3 (100×10^9/L), and absolute neutrophils count <1,500/mm^3 (1.5×10^9/L).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NrtIs	Drug: Nucleoside/nucleotide reverse transcriptase inhibitors (NrtIs); Subjects will receive NrtIs therapy for 24 weeks.
Experimental: HH-003+NrtIs	Drug: HH-003 and NrtIs; Subjects will receive HH-003 20 mg/kg intravenously Q2W and NrtIs therapy for 24 weeks.
Experimental: HH-003+NrtIs+PEG-IFN-α	Drug: HH-003, NrtIs and PEG-IFN-α; Subjects will receive HH-003 20 mg/kg intravenously Q2W, NrtIs therapy and PEG-IFN-α 180μg SC QW for 24 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of subjects with HBV DNA negativation	Week 24
Changes from baseline in serum HBsAg	From treatment start up to Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of subjects achieving maintained virologic response (MVR)	From treatment start up to 48 weeks
Duration of MVR	From treatment start up to 48 weeks
Percentage of subjects with ALT normalization	From treatment start up to 48 weeks
Changes from baseline in serum HBeAg in subjects with positive HBeAg	From treatment start up to 48 weeks

Collaborators and Investigators

• Sponsor: Huahui Health

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2022
• Primary Completion (Actual): April 24, 2023
• Study Completion (Estimated): March 31, 2024

Study Registration Dates

• First Submitted: February 9, 2023
• First Submitted That Met QC Criteria: February 9, 2023
• First Posted (Actual): February 21, 2023

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Sepsis; Hepatitis, Chronic; Hepatitis; Chronic Disease; Hepatitis B; Hepatitis B, Chronic; Viremia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Reverse Transcriptase Inhibitors
• Other Study ID Numbers: HH003-203

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No