A Clinical Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HT-101 Injection and/or HT-102 Injection in Patients With Chronic Hepatitis B Virus Infection
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 86
- Locations
- 7
- Primary Endpoint
- Clinically significant abnormalities
Study Overview
Brief Summary
This study is A multicenter, open-label, partial multiple-ascending doses phase1b/2 in which participants with chronic hepatitis B virus (HBV) infection will receive HT-101 and/or HT-102 and be assessed for safety, tolerability, Pharmacokinetics, and Pharmacodynamics. Approximately 86 patients with chronic hepatitis B infection were planned to be recruited. Among them, Group A and Group AA received HT-101 injection, administered once every 4 weeks (Q4W), at least for 24 weeks. Group B received HT-102 injection, administered Q4W for 24 weeks and sequential dosed with HT-101 for another 24 weeks. Groups C, D, and E received HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks. During the study period, all subjects received nucleoside (acid) analogues (NAs) treatment.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subjects were eligible for inclusion into the study if they met each of the following criteria:
- •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 > 100 IU/mL and <3000 IU/mL; The quantitation level of HBV DNA <LLOQ;
- •· On Nas therapy for >/= 6 months at the time of screening
- •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 cancer;
Arms & Interventions
Experimental: Cohort D (HT-101 + HT-102)
Participants will receive HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks
Intervention: HT-102 (Drug)
Experimental: Cohort A (HT-101)
Participants will receive received HT-101 injection, administered once every 4 weeks (Q4W), at least for 24 weeks
Intervention: HT-101 (Drug)
Experimental: Cohort AA (HT-101)
Participants will receive received HT-101 injection, administered once every 4 weeks (Q4W), at least for 24 weeks
Intervention: HT-101 (Drug)
Experimental: Cohort B （HT-102；HT-101）
Participants will receive HT-102 injection, administered Q4W for 24 weeks and sequential dosed with HT-101 for another 24 weeks
Intervention: HT-101 (Drug)
Experimental: Cohort B （HT-102；HT-101）
Participants will receive HT-102 injection, administered Q4W for 24 weeks and sequential dosed with HT-101 for another 24 weeks
Intervention: HT-102 (Drug)
Experimental: Cohort C (HT-101 + HT-102)
Participants will receive HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks
Intervention: HT-101 (Drug)
Experimental: Cohort C (HT-101 + HT-102)
Participants will receive HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks
Intervention: HT-102 (Drug)
Experimental: Cohort D (HT-101 + HT-102)
Participants will receive HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks
Intervention: HT-101 (Drug)
Experimental: Cohort E (HT-101 + HT-102)
Participants will receive HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks
Intervention: HT-101 (Drug)
Experimental: Cohort E (HT-101 + HT-102)
Participants will receive HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks
Intervention: HT-102 (Drug)
Outcomes
Primary Outcomes
Clinically significant abnormalities
Time Frame: From enrollment to the end of treatment at up to 60 weeks
Number of subjects with clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory parameters graded by CTCAE v5.0.
Incidence of adverse events (AEs) and serious adverse events (SAEs)
Time Frame: From enrollment to the end of treatment at up to 60 weeks
Number of subjects with adverse events (AEs) and serious adverse events (SAEs) assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Secondary Outcomes
- Maximum Change of Serum HBsAg From Baseline(Up to 48 weeks)
- Maximum Change of Serum HBV DNA From Baseline(Up to 48 weeks)
- Titers of Anti-drug Antibody (ADA) to HT-102(UP to 36 weeks)
- Maximum Plasma Concentration (Cmax)(HT-101: From predose 1 hour to postdose 24 hours HT-102：UP to 36 weeks)
- Time to Reach Maximum Plasma Concentration (Tmax)(HT-101：From predose 1 hour to postdose 24 hours. HT-102：UP to 36 weeks)
- Area Under the Plasma Concentration Versus Time Curve (AUC)(HT-101：From predose 1 hour to postdose 24 hours. HT-102：UP to 36 weeks)
- Apparent Terminal Elimination Half-life (T1/2)(HT-101：From predose 1 hour to postdose 24 hours. HT-102：UP to 36 weeks)
- Apparent Plasma Clearance (CL/F)(HT-101：From predose 1 hour to postdose 24 hours. HT-102：UP to 36 weeks)
- Apparent volume of distribution（Vd/F）(HT-101：From predose 1 hour to postdose 24 hours. HT-102：UP to 36 weeks)