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

Primary Purpose

Chronic Hepatitis b

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
ASC22
sodium chloride
Sponsored by
Ascletis Pharmaceuticals Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis b focused on measuring Chronic Hepatitis b (CHB), PD-L1, Fc fusion protein injection

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Peking University First HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

cohort1: Single dose ASC22 injection 0.3mg/kg

cohort2:Single dose ASC22 injection 1.0mg/kg

cohort3:Single dose ASC22 injection 2.5mg/kg

cohort4: Multiple dose ASC22 injection 1.0mg/kg

cohort5: Multiple dose ASC22 injection 2.5mg/kg

cohort4: Placebo sodium chloride injection A

cohort5: Placebo sodium chloride injection B

cohort6: Multiple dose ASC22 injection 1.0mg/kg

cohort6: Placebo sodium chloride injection A

Arm Description

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

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

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

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

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

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).

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).

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

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).

Outcomes

Primary Outcome Measures

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).
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).

Secondary Outcome Measures

Evaluate the decline value of HBsAg level.
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.
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.
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.
Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).

Full Information

First Posted
June 22, 2020
Last Updated
October 9, 2022
Sponsor
Ascletis Pharmaceuticals Co., Ltd.
Collaborators
Peking University First Hospital, Beijing Clinical Service Center
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1. Study Identification

Unique Protocol Identification Number
NCT04465890
Brief Title
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

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 17, 2020 (Actual)
Primary Completion Date
June 30, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ascletis Pharmaceuticals Co., Ltd.
Collaborators
Peking University First Hospital, Beijing Clinical Service Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis b
Keywords
Chronic Hepatitis b (CHB), PD-L1, Fc fusion protein injection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
208 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
cohort1: Single dose ASC22 injection 0.3mg/kg
Arm Type
Experimental
Arm Description
Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,0.3mg/kg dose of the drug once.
Arm Title
cohort2:Single dose ASC22 injection 1.0mg/kg
Arm Type
Experimental
Arm Description
Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,1.0mg/kg dose of the drug once.
Arm Title
cohort3:Single dose ASC22 injection 2.5mg/kg
Arm Type
Experimental
Arm Description
Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,2.5mg/kg dose of the drug once.
Arm Title
cohort4: Multiple dose ASC22 injection 1.0mg/kg
Arm Type
Experimental
Arm Description
Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 1.0mg/kg, up to 24 weeks
Arm Title
cohort5: Multiple dose ASC22 injection 2.5mg/kg
Arm Type
Experimental
Arm Description
Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 2.5mg/kg, up to 24 weeks
Arm Title
cohort4: Placebo sodium chloride injection A
Arm Type
Placebo Comparator
Arm 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).
Arm Title
cohort5: Placebo sodium chloride injection B
Arm Type
Placebo Comparator
Arm 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).
Arm Title
cohort6: Multiple dose ASC22 injection 1.0mg/kg
Arm Type
Experimental
Arm Description
Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 1.0mg/kg, up to 24 weeks
Arm Title
cohort6: Placebo sodium chloride injection A
Arm Type
Placebo Comparator
Arm 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).
Intervention Type
Drug
Intervention Name(s)
ASC22
Intervention Description
200mg/1ml/1bottle
Intervention Type
Drug
Intervention Name(s)
sodium chloride
Intervention Description
90mg/10ml/1 bottle
Primary Outcome Measure Information:
Title
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.
Description
Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).
Time Frame
48 weeks
Title
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.
Description
Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Evaluate the decline value of HBsAg level.
Description
Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).
Time Frame
48 weeks
Title
Evaluate the propotion's change of HBsAg < 0.05IU/ml in each cohort.
Description
Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).
Time Frame
48 weeks
Title
Evaluate the changes of cytokines (IL-2, IFN-γ) in each cohort.
Description
Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).
Time Frame
48 weeks
Title
Evaluate the changes of peripheral blood lymphocyte subsets in each cohort.
Description
Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Guiqiang Wang, MD
Phone
86-13911405123
Email
john131212@sina.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jun Li, MD
Phone
86-13520089612
Email
lijun1350089612@sina.com
Facility Information:
Facility Name
Peking University First Hospital
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guiqiang Wang, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

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