Clinical trial NCT04465890: A Phase II Study of Subcutaneously Injected PD-L1 Antibody ASC22 in Chronic Hepatitis B Patients
Official title: Phase IIa Single Dose and Phase IIb Mutiple Dose Clinical Studies to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Subcutaneously Injected PD-L1 Antibody ASC22 in Patients With Chronic Hepatitis B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis b
Keywords: Chronic Hepatitis b (CHB)
PD-L1
Fc fusion protein injection
Lead sponsor: Ascletis Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Peking University First Hospital
name: Beijing Clinical Service Center
First posted: 2020-07-10
Enrollment: 207
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 48 weeks
measure: 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.
timeFrame: 48 weeks
Secondary outcomes:
measure: Evaluate the decline value of HBsAg level.
timeFrame: 48 weeks
measure: Evaluate the propotion's change of HBsAg < 0.05IU/ml in each cohort.
timeFrame: 48 weeks
measure: Evaluate the changes of cytokines (IL-2, IFN-γ) in each cohort.
timeFrame: 48 weeks
measure: Evaluate the changes of peripheral blood lymphocyte subsets in each cohort.
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital
Study officials:
References: