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

• ClinicalTrials.gov Identifier: NCT04465890
• Recruitment Status: Active, not recruiting
• First Posted: July 10, 2020
• Last Update Posted: April 3, 2024
• Sponsor: Ascletis Pharmaceuticals Co., Ltd.
• Collaborators: Peking University First Hospital; Beijing Clinical Service Center
• Information provided by (Responsible Party): Ascletis Pharmaceuticals Co., Ltd.

Tracking Information

• First Submitted Date: June 22, 2020
• First Posted Date: July 10, 2020
• Last Update Posted Date: April 3, 2024
• Actual Study Start Date: July 17, 2020
• Estimated Primary Completion Date: August 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 9, 2020)

• 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. [ Time Frame: 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. [ Time Frame: 48 weeks ]
  Each multiple dose cohort will last 48 weeks (24-weeks treatment plus 24-weeks follow up).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 9, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Chronic Hepatitis b

Intervention

• Drug: ASC22
  200mg/1ml/1bottle
• Drug: sodium chloride
  90mg/10ml/1 bottle

Study Arms

• Experimental: cohort1: Single dose ASC22 injection 0.3mg/kg
  Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,0.3mg/kg dose of the drug once.
  Intervention: Drug: ASC22
• Experimental: cohort2:Single dose ASC22 injection 1.0mg/kg
  Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,1.0mg/kg dose of the drug once.
  Intervention: Drug: ASC22
• Experimental: cohort3:Single dose ASC22 injection 2.5mg/kg
  Single dose ASC22 Injection; Specification: 200mg/1ml/1bottle; Subcutaneous injection; once administration,2.5mg/kg dose of the drug once.
  Intervention: Drug: ASC22
• Experimental: cohort4: Multiple dose ASC22 injection 1.0mg/kg
  Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 1.0mg/kg, up to 24 weeks
  Intervention: Drug: ASC22
• Experimental: cohort5: Multiple dose ASC22 injection 2.5mg/kg
  Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 2.5mg/kg, up to 24 weeks
  Intervention: Drug: ASC22
• Placebo Comparator: cohort4: Placebo sodium chloride injection A
  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: Drug: sodium chloride
• Placebo Comparator: cohort5: Placebo sodium chloride injection B
  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).
  Intervention: Drug: sodium chloride
• Experimental: cohort6: Multiple dose ASC22 injection 1.0mg/kg
  Multiple dose ASC22 injection; Specification: 200mg/1ml/1bottle; Subcutaneously administered once every 2 weeks , 4 received 1.0mg/kg, up to 24 weeks
  Intervention: Drug: ASC22
• Placebo Comparator: cohort6: Placebo sodium chloride injection A
  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: Drug: sodium chloride

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 2, 2024): 207
• Original Estimated Enrollment (submitted: July 9, 2020): 159
• Estimated Study Completion Date: August 30, 2024
• Estimated Primary Completion Date: August 30, 2024 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04465890
• Other Study ID Numbers: ASC-ASC22-II-CTP-01
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Ascletis Pharmaceuticals Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Ascletis Pharmaceuticals Co., Ltd.
• Original Study Sponsor: Same as current

Collaborators

• Peking University First Hospital
• Beijing Clinical Service Center

• Investigators: Not Provided
• PRS Account: Ascletis Pharmaceuticals Co., Ltd.
• Verification Date: April 2024