A Phase II Study of Subcutaneously Injected PD-L1 Antibody ASC22 in Chronic Hepatitis B Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Chronic Hepatitis b

Intervention / Treatment
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* Drug: ASC22
* Drug: sodium chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-65 years old (including boundary value), gender unlimited； Chronic hepatitis B patients with clear diagnosis of Hematology, etiology and clinical (for example: HBsAg positive for more than 6 months); HBV-DNA turns negative after treatment with nucleoside (acid) drugs; cohort1-5:HBsAg≤ 10000 IU/mL; cohort6: HBsAg≤ 100 IU/mL; HBeAg negative; 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: 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); 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); Liver cancer patients or blood AFP>1×ULN; cohort1-5：Patients who received interferon therapy within 6 months before the first administration; cohort6: Patients who received interferon therapy before the first administration; Patients receiving immunosuppressive therapy within 3 months before the first administration (except interferon); The investigator judges that the participants are not suitable for this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cohort1: Single dose ASC22 injection 0.3mg/kg<br>Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,0.3mg/kg dose of the drug once. | Drug: ASC22<br>* 200mg/1ml/1bottle<br>|
| Experimental: cohort2:Single dose ASC22 injection 1.0mg/kg<br>Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,1.0mg/kg dose of the drug once. | Drug: ASC22<br>* 200mg/1ml/1bottle<br>|
| Experimental: cohort3:Single dose ASC22 injection 2.5mg/kg<br>Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,2.5mg/kg dose of the drug once. | Drug: ASC22<br>* 200mg/1ml/1bottle<br>|
| Experimental: cohort4: Multiple dose ASC22 injection 1.0mg/kg<br>Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 1.0mg/kg, up to 24 weeks | Drug: ASC22<br>* 200mg/1ml/1bottle<br>|
| Experimental: cohort5: Multiple dose ASC22 injection 2.5mg/kg<br>Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 2.5mg/kg, up to 24 weeks | Drug: ASC22<br>* 200mg/1ml/1bottle<br>|
| Placebo Comparator: cohort4: Placebo sodium chloride injection A<br>Placebo saline injection; Specification: 90mg/10ml/1 bottle; Subcutaneously administered every 2 weeks (Q2W, known as one drug administration cycle), duration: once every 2 weeks (Q2W), up to 12 weeks. Based on the weight of the patients, an equal dose of placebo was administered according to the incoming dose group (1.0mg/kg). | Drug: sodium chloride<br>* 90mg/10ml/1 bottle<br>|
| Placebo Comparator: cohort5: Placebo sodium chloride injection B<br>Placebo saline injection; Specification: 90mg/10ml/1 bottle; Subcutaneously administered every 2 weeks (Q2W, known as one drug administration cycle), duration: once every 2 weeks (Q2W), up to 12 weeks. Based on the weight of the patients, an equal dose of placebo was administered according to the incoming dose group (2.5mg/kg). | Drug: sodium chloride<br>* 90mg/10ml/1 bottle<br>|
| Experimental: cohort6: Multiple dose ASC22 injection 1.0mg/kg<br>Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 1.0mg/kg, up to 24 weeks | Drug: ASC22<br>* 200mg/1ml/1bottle<br>|
| Placebo Comparator: cohort6: Placebo sodium chloride injection A<br>Placebo saline injection; Specification: 90mg/10ml/1 bottle; Subcutaneously administered every 2 weeks (Q2W, known as one drug administration cycle), duration: once every 2 weeks (Q2W), up to 12 weeks. Based on the weight of the patients, an equal dose of placebo was administered according to the incoming dose group (1.0mg/kg). | Drug: sodium chloride<br>* 90mg/10ml/1 bottle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up). | 48 weeks | 
| 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. | Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up). | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the decline value of HBsAg level. | Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up). | 48 weeks | 
| Evaluate the propotion's change of HBsAg < 0.05IU/ml in each cohort. | Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up). | 48 weeks | 
| Evaluate the changes of cytokines (IL-2, IFN-γ) in each cohort. | Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up). | 48 weeks | 
| Evaluate the changes of peripheral blood lymphocyte subsets in each cohort. | Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up). | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Hepatitis b (CHB), PD-L1, Fc fusion protein injection