Chronic Hepatitis b
Conditions
Keywords
Chronic Hepatitis b (CHB), PD-L1, Fc fusion protein injection
Brief summary
The objective of this study is to evaluate the safety and efficacy of ASC22 in the treatment of chronic hepatitis B after single and multiple drug administration.
Detailed description
The study consists of two parts: the ASC22 single-dose IIa study and the ASC22 multi-dose IIb study. The IIa study consists of 3 cohorts of 0.3mg/kg, 1.0mg/kg and 2.5mg/kg, and the IIb study consists of 2 cohorts of 1.0mg/kg and 2.5mg/kg. The objective is to evaluate the safety, tolerance and efficacy of ASC22 in patients with chronic hepatitis B (CHB), and to provide a guidance for the determination of dosage regimen.
Interventions
DRUGASC22
200mg/1ml/1bottle
DRUGsodium chloride
90mg/10ml/1 bottle
Sponsors
Peking University First Hospital
Beijing Clinical Service Center
Ascletis Pharmaceuticals Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. 18-65 years old (including boundary value), gender unlimited； 2. Chronic hepatitis B patients with clear diagnosis of Hematology, etiology and clinical (for example: HBsAg positive for more than 6 months); 3. HBV-DNA turns negative after treatment with nucleoside (acid) drugs; 4. cohort1-5:HBsAg≤ 10000 IU/mL; cohort6: HBsAg≤ 100 IU/mL; 5. HBeAg negative; 6. The fertile female subjects or the fertile male subjects agreed to take contraceptive measures from 7 days before the first administration until 24 weeks after the end of the administration cycle of ASC22. The serum pregnancy test of fertile female subjects must be negative within 7 days before the first administration.
Exclusion criteria
1. Patients with hepatitis a, hepatitis c (HCV RNA\>15IU/L), hepatitis d or HIV infection; Patients with other active infections (e.g., respiratory tract infection, urinary tract infection and herpes simplex, cytomegalovirus, epstein-barr virus); 2. Fibrosis stage: Cirrhosis, portal hypertension, or advanced fibrosis (defined as Fibroscan≥9.5kPa or ARFI≥1.81m/sec or Fibrosis-4 (FIB-4)≥3.25 or METAVIR F≥3); 3. Liver cancer patients or blood AFP\>1×ULN; 4. cohort1-5：Patients who received interferon therapy within 6 months before the first administration; cohort6: Patients who received interferon therapy before the first administration; 5. Patients receiving immunosuppressive therapy within 3 months before the first administration (except interferon); 6. The investigator judges that the participants are not suitable for this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the decreased HBsAg levels at 12 or 24 weeks of treatment or at 4, 12, or 24 weeks of follow-up visits compared with baseline. | 48 weeks | Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up). |
| Evaluate the number of patients with ≥0.5log reduction in HBsAg log10IU/ mL at 12 or 24 weeks of treatment, or at 4, 12, or 24 weeks of follow-up visits compared with baseline. | 48 weeks | Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the decline value of HBsAg level. | 48 weeks | Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up). |
| Evaluate the propotion's change of HBsAg < 0.05IU/ml in each cohort. | 48 weeks | Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up). |
| Evaluate the changes of cytokines (IL-2, IFN-γ) in each cohort. | 48 weeks | Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up). |
| Evaluate the changes of peripheral blood lymphocyte subsets in each cohort. | 48 weeks | Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up). |
Countries
China
Outcome results
None listed