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

Ascletis

Status and phase: Completed; Phase 2

Conditions: Chronic Hepatitis b

Treatments: Drug: ASC22; Drug: sodium chloride

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04465890

ASC-ASC22-II-CTP-01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 207 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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207 participants in 9 patient groups, including a placebo group

cohort1: Single dose ASC22 injection 0.3mg/kg

Experimental group

Description:

Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,0.3mg/kg dose of the drug once.

Treatment:

Drug: ASC22

cohort2:Single dose ASC22 injection 1.0mg/kg

Experimental group

Description:

Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,1.0mg/kg dose of the drug once.

Treatment:

Drug: ASC22

cohort3:Single dose ASC22 injection 2.5mg/kg

Experimental group

Description:

Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,2.5mg/kg dose of the drug once.

Treatment:

Drug: ASC22

cohort4: Multiple dose ASC22 injection 1.0mg/kg

Experimental group

Description:

Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 1.0mg/kg, up to 24 weeks

Treatment:

Drug: ASC22

cohort5: Multiple dose ASC22 injection 2.5mg/kg

Experimental group

Description:

Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 2.5mg/kg, up to 24 weeks

Treatment:

Drug: ASC22

cohort4: Placebo sodium chloride injection A

Placebo Comparator group

Description:

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).

Treatment:

Drug: sodium chloride

cohort5: Placebo sodium chloride injection B

Placebo Comparator group

Description:

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).

Treatment:

Drug: sodium chloride

cohort6: Multiple dose ASC22 injection 1.0mg/kg

Experimental group

Description:

Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 1.0mg/kg, up to 24 weeks

Treatment:

Drug: ASC22

cohort6: Placebo sodium chloride injection A

Placebo Comparator group

Description:

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).

Treatment:

Drug: sodium chloride