This is a Phase 1 Study in Which Healthy Volunteers and Participants with Chronic HBV Infection Will Receive HT-101 or Placebo and Will Be Assessed for Safety, Tolerability, Pharmacokinetics (PK), and Antiviral Activity

Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Characteristics of HT-101 Injection in Healthy Subjects and Patients with Chronic Hepatitis B Virus Infection: a Randomized, Double-blind, Placebo-controlled, Single and Multiple Doses, and Dose Escalation Phase 1 Clinical Study

Phase 1 Study of HT-101 in Healthy Subjects and Patients With Chronic Hepatitis B The trial consisted of two components. Part A involved a single ascending dose study where healthy participants were administered one dose of HT-101 or placebo subcutaneously (SC). Part B involved a multiple ascending dose study where participants with chronic hepatitis B virus infection were administered two dose of HT-101 or placebo every 4 weeks subcutaneously (SC).

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: HT-101; Drug: HT-101; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital
    • Beijing, Beijing, China, 100015
      • Beijing Ditan Hospital Capital Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221132
      • The Affiliated Hospital of Xuzhou Medical University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Bethune Hospital of Jilin University
    • Yanji, Jilin, China, 133000
      • Yanbian University Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200083
      • Shanghai Public Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria: Subjects were eligible for inclusion into the study if they met each of the following criteria:

Part A SAD: Healthy Participant

• Male participants weighed ≥ 50.0 kg, female participants weighed ≥ 45.0 kg;
• Participants who promise having used effective contraception for at least 1 month before screening, and have no plans for pregnancy or donating sperm or eggs, and will voluntarily use effective physical means of contraception (including the partner) during the study and for 3 months after the end of the study;

Part B MAD: Patient with CHB

• Male subjects weighed ≥ 50.0 kg, female subjects weighed ≥ 45.0 kg, with a body mass index (BMI) between 19.0 and 28.0 kg/m^2 (inclusive);
• Chronic HBV infection for >/= 6 months;
• The quantitation level of HBsAg was > 200 IU/mL and < 5000 IU/mL; The quantitation level of HBV DNA < 2×10^4 IU/mL;
• Subjects promised to use effective contraception for at least 1 month before screening, and have no fertility, donate sperm or eggs and voluntarily take highly effective physical contraception (including partners) during the trial and within 3 months after the end of the trial;

Exclusion Criteria:Subjects were excluded from the study if one or more of the following criteria were applicable

• Participants with history of drug allergy or specific allergy;
• Participants who had psychiatric conditions or diseases in cardiovascular, respiratory, endocrine, kidney, liver, digestive tract, skin, immune, blood, nerve and other systems;
• Participants with history of active pathological bleeding, or bleeding tendency;
• Participants with abnormal results of physical examination, vital sign examination, ECG examination, laboratory test in the screening period which were judged as clinically significant by clinicians;
• Participants with significant liver fibrosis or cirrhosis;
• Participants with symptoms or a history of hepatic decompensation;
• Participants with a history or suspected risk of liver cancerr;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A; Single ascending Dose of HT-101 or placebo in Healthy participants subcustaneously.	Drug: HT-101; Single dose of HT-101 administered subcutaneously.; Drug: HT-101; Multiple dose of HT-101 administered subcutaneously.; Drug: Placebo; Placebo, containing no active ingredient, administered subcutaneouly
Experimental: Part B; Multiple Ascending Dose of HT-101 or placebo in patients with Chronic hepatitis B virus subcustaneously.	Drug: HT-101; Single dose of HT-101 administered subcutaneously.; Drug: HT-101; Multiple dose of HT-101 administered subcutaneously.; Drug: Placebo; Placebo, containing no active ingredient, administered subcutaneouly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs) and serious adverse events (SAEs)	Number of subjects with adverse events (AEs) and serious adverse events (SAEs) assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.	From enrollment to the end of treatment at 24 weeks
Clinically significant abnormalities	Number of subjects with clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory parameters graded by CTCAE v5.0.	From enrollment to the end of treatment at 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (Cmax)	Cmax of HT-101 and its metabolite in plasma. First administration (Healty participants and Patients with CHB): Predose 0.5 hours; Postdose 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours and 48 hours. Second administration (Patients with CHB): Predose 0.5 hours; postdose 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours and 48 hours.	From predose 0.5 hours to postdose 48 hours.
Time to Reach Maximum Plasma Concentration (Tmax)	Tmax of HT-101 and its metabolite in plasma. First administration (Healty participants and Patients with CHB): Predose 0.5 hours; Postdose 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours and 48 hours. Second administration (Patients with CHB): Predose 0.5 hours; postdose 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours and 48 hours.	From predose 0.5 hours to postdose 48 hours.
Area Under the Plasma Concentration Versus Time Curve (AUC)	AUC of HT-101 and its metabolite from time 0 to last measurable time. First administration (Healty participants and Patients with CHB): Predose 0.5 hours; Postdose 0.5 hours,1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours and 48 hours. Second administration (Patients with CHB): Predose 0.5 hours; postdose 0.5 hours,1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours and 48 hours.	From predose 0.5 hours to postdose 48 hours.
Apparent Terminal Elimination Half-life (T1/2)	T1/2 of HT-101 in plasma. First administration (Healty participants and Patients with CHB): Predose 0.5 hours; Postdose 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours and 48 hours. Second administration (Patients with CHB): Predose 0.5 hours; postdose 0.5 hours, 1hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours and 48 hours.	From predose 0.5 hours to postdose 48 hours.
Apparent Plasma Clearance (CL/F)	CL/F of HT-101 in plasma. First administration (Healty participants and Patients with CHB): Predose 0.5 hours; Postdose 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours and 48 hours. Second administration (Patients with CHB): Predose 0.5 hours; postdose 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours and 48 hours.	From predose 0.5 hours to postdose 48 hours.
apparent volume of distribution（Vd/F）	Vd/F of HT-101. First administration (Healty participants and Patients with CHB): Predose 0.5 hours; Postdose 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours and 48 hours. Second administration (Patients with CHB): Predose 0.5 hours; postdose 0.5 hours, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 10 hours, 12 hours, 24 hours and 48 hours.	From predose 0.5 hours to postdose 48 hours.
Maximum Change of Serum HBsAg From Baseline	Maximum change of serum HBsAg from Day 1 until 24 weeks post last dose (negative values mean reductions from baseline, positive values mean increased from baseline)	Up to 24 weeks
Maximum Change of Serum HBV DNA From Baseline	Maximum change of serum HBV DNA from Day 1 until 24 weeks (negative values mean reductions from baseline, positive values mean increased from baseline).	Up to 24 weeks
Number of participants with HBeAg Loss	For HBeAg-positive Participants: Number of Subjects With HBeAg Loss	Up to 24 weeks

Collaborators and Investigators

• Sponsor: Suzhou HepaThera Biotech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2022
• Primary Completion (Actual): May 13, 2024
• Study Completion (Actual): June 17, 2024

Study Registration Dates

• First Submitted: December 9, 2024
• First Submitted That Met QC Criteria: December 19, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis; Hepatitis B; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: HT-101-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes