Chronic Hepatitis B
Conditions
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.
Interventions
Sponsors
Suzhou HepaThera Biotech Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinically significant abnormalities | 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | AUC of HT-101 and its metabolite from time 0 to last measurable time. First administration: Predose 1 hour; Postdose 0.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours. Changes in the concentration of and HT-102 in serum, From Day1 until 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 | T1/2 of HT-101 in plasma. First administration: Predose 1 hour; Postdose 0.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours. Changes in the concentration of and HT-102 in serum, From Day1 until 36 weeks |
| Apparent Plasma Clearance (CL/F) | HT-101：From predose 1 hour to postdose 24 hours. HT-102：UP to 36 weeks | CL/F of HT-101 in plasma. First administration: Predose 1 hour; Postdose 0.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours. Changes in the concentration of and HT-102 in serum, From Day1 until 36 weeks |
| Maximum Plasma Concentration (Cmax) | HT-101: From predose 1 hour to postdose 24 hours HT-102：UP to 36 weeks | Cmax of HT-101 and its metabolite in plasma. First administration: Predose 1 hour; Postdose 0.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours. Changes in the concentration of and HT-102 in serum, From Day1 until 36 weeks |
| Maximum Change of Serum HBsAg From Baseline | Up to 48 weeks | Maximum change of serum HBsAg from Day 1 until 48 weeks post last dose (negative values mean reductions from baseline, positive values mean increased from baseline) |
| Maximum Change of Serum HBV DNA From Baseline | Up to 48 weeks | Maximum change of serum HBV DNA from Day 1 until 48 weeks (negative values mean reductions from baseline, positive values mean increased from baseline). |
| Titers of Anti-drug Antibody (ADA) to HT-102 | UP to 36 weeks | ADA analysis for predose 36weeks |
| Apparent volume of distribution（Vd/F） | HT-101：From predose 1 hour to postdose 24 hours. HT-102：UP to 36 weeks | Vd/F of HT-101. First administration: Predose 1 hour; Postdose 0.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours. Changes in the concentration of and HT-102 in serum, From Day1 until 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 | Tmax of HT-101 and its metabolite in plasma. First administration: Predose 1 hour; Postdose 0.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours. Changes in the concentration of and HT-102 in serum, From Day1 until 36 weeks |
Countries
China
Outcome results
None listed