A Study to Evaluate the Antiviral Activity and Safety of HH-003 Injection in Subjects With HBeAg-Negative Chronic Hepatitis B Treated With Nucleos(t)Ide Reverse Transcriptase Inhibitors

A Multicenter, Randomized, Controlled Phase IIa Study to Evaluate the Antiviral Activity and Safety of HH-003 Injection in Subjects With HBeAg-Negative Chronic Hepatitis B Treated With Nucleos(t)Ide Reverse Transcriptase Inhibitors

This is a multicenter, randomized, controlled Phase IIa study of HH-003 injection, HH-003 injection is a monoclonal antibody targeting Hepatitis B virus. This study aims to evaluate the antiviral activity and safety in subjects with with HBeAg-negative Chronic Hepatitis B treated with nucleos(t)ide reverse transcriptase inhibitors.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: NrtIs; Drug: HH-003; Drug: HH-003+NrtIs

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital, Southern Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent form;
• Male or female aged from 18 to 65years (inclusively);
• 18 kg/m^2≤BMI≤32 kg/m^2, body weight≥45 kg for men and ≥40 kg for women;
• At screening, etiological, clinical, or pathological evidence indicates chronic hepatitis B virus infection for at least 6 months; and negative HBeAg for more than 6 months; 10 IU/mL≤HBsAg≤3000 IU/mL; HBV DNA≤20 IU/mL; ALT≤1×ULN;
• Participants who have been on the treatment of nucleos(t)ide reverse transcriptase inhibitors (limited to entecavir [ETV], tenofovir disoproxil fumarate [TDF], or tenofovir alafenamide fumarate [TAF]) for at least 3 years (as judged by the investigator) at screening.

Exclusion Criteria:

• Females who are pregnant or lactating at screening;
• History of alcoholic liver disease, non-alcoholic steatohepatitis, autoimmune liver disease, other hereditary liver disease, drug-induced liver disease or other clinically significant chronic liver disease induced by non-HBV infection;
• History or presence of progressive liver fibrosis or cirrhosis, including but not limited to liver stiffness measurement [LSM] ≥ 9 kPa at screening, progressive liver fibrosis or cirrhosis (e.g., S ≥ 3 in GS score or METAVIR ≥ F3) by liver histopathology examination, according to the Consensus on the diagnosis and therapy of hepatic fibrosis [2019]; or the presence of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, or esophageal and gastric varices.
• History or presence of hepatocellular carcinoma, or alpha-fetoprotein (AFP) ≥ 50 ng/mL at screening; or suspicion of hepatocellular carcinoma indicated by liver ultrasound, CT, or MRI.
• Use of antiviral therapy with interferon within 1 year prior to screening
• Any of the following lab test 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), Serum albumin < 35 g/L; international normalized ratio (INR) of prothrombin time > 1.3; or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2.

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: NrtIs; Subjects will receive NrtIs therapy for 24 weeks.
Experimental: HH-003+NrtIs	Drug: HH-003+NrtIs; Subjects will receive HH-003 20 mg/kg intravenously Q2W for 24 weeks. Subjects will receive NrtIs therapy for 24 weeks.
Experimental: HH-003	Drug: HH-003; Subjects will receive HH-003 20 mg/kg intravenously Q2W for 24 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of participants achieving sustained viral response	From baseline to Week 24
Changes from baseline in serum HBsAg levels	From treatment start to Week 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of participants with undetectable HBV DNA in those with positive HBV DNA at baseline	From treatment start to Week 24
Proportion of participants achieving sustained viral response	From baseline to Week 48
Duration of sustained viral response	From treatment start to Week 48
Changes from baseline in serum HBsAg levels	From treatment start up to Week 48
Proportion of participants with HBV pgRNA negativation in those with positive HBV pgRNA at baseline	From baseline to Week 24
Proportion of participants with normal ALT levels	From treatment start to Week 48

Collaborators and Investigators

• Sponsor: Huahui Health

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2021
• Primary Completion (Actual): December 5, 2022
• Study Completion (Actual): May 17, 2023

Study Registration Dates

• First Submitted: April 20, 2023
• First Submitted That Met QC Criteria: April 20, 2023
• First Posted (Actual): May 3, 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; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: HH003-202

Drug and device information, study documents

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