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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental: Cohort A (HT-101) | Experimental | Participants will receive received HT-101 injection, administered once every 4 weeks (Q4W), at least for 24 weeks |
|
| Experimental: Cohort AA (HT-101) | Experimental | Participants will receive received HT-101 injection, administered once every 4 weeks (Q4W), at least for 24 weeks |
|
| Experimental: Cohort B (HT-102;HT-101) | Experimental | Participants will receive HT-102 injection, administered Q4W for 24 weeks and sequential dosed with HT-101 for another 24 weeks |
|
| Experimental: Cohort C (HT-101 + HT-102) | Experimental | Participants will receive HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks |
|
| Experimental: Cohort D (HT-101 + HT-102) | Experimental | Participants will receive HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HT-101 | Drug | HT-101 given by subcutaneous injection. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 up to 60 weeks |
| 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 up to 60 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Plasma Concentration (Cmax) | 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 | HT-101: From predose 1 hour to postdose 24 hours HT-102:UP to 36 weeks |
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Inclusion 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:
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;
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Ditan Hospital Capital Medical University | Beijing | Beijing Municipality | 100015 | China | ||
| Xiamen Hospital of Traditional Chinese Medicine |
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| ID | Term |
|---|---|
| D019694 | Hepatitis B, Chronic |
| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
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| Experimental: Cohort E (HT-101 + HT-102) | Experimental | Participants will receive HT-101 injection combined with HT-102 injection, administered once every 4 weeks for 24weeks |
|
| HT-102 | Drug | HT-102 given by subcutaneous injection. |
|
| Time to Reach Maximum Plasma Concentration (Tmax) | 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 | 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) | 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 | HT-101:From predose 1 hour to postdose 24 hours. HT-102:UP to 36 weeks |
| Apparent Terminal Elimination Half-life (T1/2) | 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 | HT-101:From predose 1 hour to postdose 24 hours. HT-102:UP to 36 weeks |
| Apparent Plasma Clearance (CL/F) | 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 | HT-101:From predose 1 hour to postdose 24 hours. HT-102:UP to 36 weeks |
| Apparent volume of distribution(Vd/F) | 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 | HT-101:From predose 1 hour to postdose 24 hours. HT-102:UP to 36 weeks |
| Maximum Change of Serum HBsAg From Baseline | 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) | Up to 48 weeks |
| Maximum Change of Serum HBV DNA From Baseline | Maximum change of serum HBV DNA from Day 1 until 48 weeks (negative values mean reductions from baseline, positive values mean increased from baseline). | Up to 48 weeks |
| Titers of Anti-drug Antibody (ADA) to HT-102 | ADA analysis for predose 36weeks | UP to 36 weeks |
| Xiamen |
| Fujian |
| 361001 |
| China |
| Guangzhou Eighth People's Hospital, Guangzhou Medical University | Guangzhou | Guangdong | 510440 | China |
| Nanfang Hospital | Guangzhou | Guangdong | 510515 | China |
| Qingyuan People's Hospital | Qingyuan | Guangdong | 511518 | China |
| Shanghai Public Health Clinical Center | Shanghai | Shanghai Municipality | 200083 | China |
| Sichuan Provincial People's Hospital | Chengdu | Sichuan | 610072 | China |
| D018347 |
| Hepadnaviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006521 | Hepatitis, Chronic |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |