Chronic Hepatitis B
Conditions
Brief summary
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).
Interventions
DRUGHT-101
Single dose of HT-101 administered subcutaneously.
DRUGPlacebo
Placebo, containing no active ingredient, administered subcutaneouly
Sponsors
Suzhou HepaThera Biotech Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events (AEs) and serious adverse events (SAEs) | From enrollment to the end of treatment at 24 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. |
| Clinically significant abnormalities | From enrollment to the end of treatment at 24 weeks | Number of subjects with clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory parameters graded by CTCAE v5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Versus Time Curve (AUC) | From predose 0.5 hours to postdose 48 hours. | 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. |
| Apparent Terminal Elimination Half-life (T1/2) | From predose 0.5 hours to postdose 48 hours. | 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. |
| Apparent Plasma Clearance (CL/F) | From predose 0.5 hours to postdose 48 hours. | 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. |
| Maximum Plasma Concentration (Cmax) | From predose 0.5 hours to postdose 48 hours. | 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. |
| Maximum Change of Serum HBsAg From Baseline | Up to 24 weeks | 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) |
| Maximum Change of Serum HBV DNA From Baseline | Up to 24 weeks | Maximum change of serum HBV DNA from Day 1 until 24 weeks (negative values mean reductions from baseline, positive values mean increased from baseline). |
| Number of participants with HBeAg Loss | Up to 24 weeks | For HBeAg-positive Participants: Number of Subjects With HBeAg Loss |
| apparent volume of distribution（Vd/F） | From predose 0.5 hours to postdose 48 hours. | 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. |
| Time to Reach Maximum Plasma Concentration (Tmax) | From predose 0.5 hours to postdose 48 hours. | 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. |
Countries
China
Outcome results
None listed