ASC22 Combined With Peg-IFNa in Achieving Functional Cure in Patients With Chronic Hepatitis B Virus Infection

Exploring the safety and efficacy of the therapy combining immune checkpoint inhibitors (anti-PD-L1 monoclonal antibody, ASC22) and pegylated interferon alfa (Peg-IFNα) in patients with CHB. Exploring new combination therapeutic schemes for hepatitis B cure, and raising the overall clinical cure rate to more than 50% without screening specific advantageous groups.

Study Overview

• Status: Recruiting
• Conditions: Chronic Hepatitis b
• Intervention / Treatment: Drug: Peg-IFNα; Drug: Anti-PD-L1 antibody (ASC22); Drug: Nucleotide analogs

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Dachuan Cai, MD; Phone Number: +86 18323409779; Email: cqmucdc@cqmu.edu.cn
• Study Contact Backup: Name: Min Chen, PhD; Phone Number: +86 17338600343; Email: mchen@hospital.cqmu.edu.cn

Study Locations

• China
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400010
      • Recruiting
      • The 2nd affiliated Hospital of Chongqing Medical University
      • Principal Investigator: HONG REN
      • Contact: Dachuan Cai; Phone Number: +8618323409779; Email: cqmucdc@cqmu.edu.cn
      • Contact: HONG REN; Phone Number: +8613983888786; Email: renhong0531@vip.sina.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Sign the informed consent form before inclusion and be able to complete the study according to the study requirements
2. From inclusion to 30 days after the last administration of the study drug, male subjects or female subjects of childbearing age are willing to voluntarily take effective contraceptive measures
3. 18-70 years old. The weight of male subjects is not less than 45 kg, and the weight of female subjects is not less than 40 kg. Body mass index (BMI) is within the range of 18-32 kg/m2
4. Serum HBsAg<100 IU/mL
5. HBV DNA<20 IU/mL
6. HBeAg-negative

Exclusion Criteria:

1. A history of allergy, or who are suspected by the researcher to be allergic to the active ingredient of the drug under study or its excipients
2. Use of inhibitors, inducers or substrates of CYP3A4 within 28 days before enrollment
3. Systematical use of immunosuppressants, immunomodulators (thymosin) and cytotoxic drugs within 6 months before enrollment, or vaccination of live attenuated vaccine within 1 month before enrollment
4. Acute infection within 2 weeks before enrollment which requires intravenous antibiotic treatment, or existing infection which requires anti-infection treatment when enrollment
5. Clinically significant acute and chronic liver disease not caused by HBV infection (judged by reseachers)
6. Confirmed or suspected decompensated cirrhosis, including but not limited to: hepatic encephalopathy, hepatorenal syndrome, bleeding from esophageal varices, splenomegaly, ascites, etc, or evidence of progressive liver fibrosis
7. Primary liver cancer, or alpha-fetoprotein (AFP) is greater than 50 ug/L or imaging suggests the possibility of malignant liver lesions, or other malignant tumors or a history of other malignant tumors within 5 years before enrollment (except that the malignant tumors have been completely relieved after treatment and patients have not received additional medical or surgical intervention within 3 years before screening)
8. A history of pathological fracture or osteoporosis
9. Gastrointestinal dysfunction or gastrointestinal diseases that might affect the absorption of oral drugs, such as severe gastric ulcer, erosive gastritis, partial gastrectomy, and persistent gastrointestinal symptoms (such as nausea, vomiting, or diarrhea) >2 grades
10. Serious diseases of circulatory, respiratory, urinary, blood, metabolic, immune, mental, neurological, renal and other systems
11. Major trauma or major surgery within 3 months before enrollment, or planned surgery during the study period
12. Blood donation/loss ≥ 400 mL within 3 months before enrollment, or given a blood transfusion within 3 months before enrollment, or blood donation/loss ≥ 200 mL within 1 month before enrollment
13. Platelet count<90 × 10^9/L, white blood cell count<3.0 × 10^9/L, neutrophil count<1.3 × 10^9/L, total serum bilirubin>2 × ULN, albumin<30 g/L, creatinine clearance ≤ 60 mL/min (calculated by CKD-EPI formula), or international normalized ratio of prothrombin time (INR)>1.5 (unless receiving stable anticoagulant therapy)
14. HCV antibody (+), HIV antigen/antibody (+), or treponema pallidum antibody (+) and RPR test (+)
15. A history of continuous alcohol abuse within 3 years before enrollment (average daily alcohol consumption exceeds 20 gram)
16. A history of drug dependence or drug abuse within 1 year before enrollment
17. Those who have participated in clinical trials of other investigational drugs or medical devices and taken investigational drugs or used medical devices within 3 months before enrollment
18. Female in suckling period or pregnancy test (+) during screening
19. Subjects who are considered by the researcher to have other factors that are not suitable for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Nucleotide analogs combined with anti-PD-L1 antibody (ASC22). Drug: Anti-PD-L1 antibody Once two weeks, 1mg/kg, subcutaneous injection for the first 24 weeks Drug: Nucleotide analogs Once/day, 1 capsule/time, oral	Drug: Anti-PD-L1 antibody (ASC22); Once two weeks, 1mg/kg, subcutaneous injection; Drug: Nucleotide analogs; Once/day, 1 capsule/time, oral; Other Names: Entecavir; Tenofovir disoproxil fumarate; Tenofovir alafenamide fumarate
Experimental: Cohort 2; Anti-PD-L1 antibody/pegylated interferon alfa (Peg-IFNα) combined with nucleotide analogs Drug: Anti-PD-L1 antibody Once two weeks, 1mg/kg, subcutaneous injection for the first 24 weeks Drug: Peg-IFNα Once/week, 180μg/time, subcutaneous injection for the second 24 weeks Drug: nucleotide analogs Once/day, 1 capsule/time, oral	Drug: Peg-IFNα; Once/week, 180μg/time, subcutaneous injection; Drug: Anti-PD-L1 antibody (ASC22); Once two weeks, 1mg/kg, subcutaneous injection; Drug: Nucleotide analogs; Once/day, 1 capsule/time, oral; Other Names: Entecavir; Tenofovir disoproxil fumarate; Tenofovir alafenamide fumarate
Experimental: Cohort 3; Peg-IFNα/Anti-PD-L1 antibody combined with nucleotide analogs Drug: Anti-PD-L1 antibody Once two weeks, 1mg/kg, subcutaneous injection for the second 24 weeks Drug: Peg-IFNα Once/week, 180μg/time, subcutaneous injection for the first 24 weeks Drug: nucleotide analogs Once/day, 1 capsule/time, oral	Drug: Peg-IFNα; Once/week, 180μg/time, subcutaneous injection; Drug: Anti-PD-L1 antibody (ASC22); Once two weeks, 1mg/kg, subcutaneous injection; Drug: Nucleotide analogs; Once/day, 1 capsule/time, oral; Other Names: Entecavir; Tenofovir disoproxil fumarate; Tenofovir alafenamide fumarate
Experimental: Cohort 4; Peg-IFNα combined with nucleotide analogs Drug: Peg-IFNα Once/week, 180μg/time, subcutaneous injection for 48 weeks Drug: nucleotide analogs Once/day, 1 capsule/time, oral	Drug: Peg-IFNα; Once/week, 180μg/time, subcutaneous injection; Drug: Nucleotide analogs; Once/day, 1 capsule/time, oral; Other Names: Entecavir; Tenofovir disoproxil fumarate; Tenofovir alafenamide fumarate
Experimental: Cohort 5; Nucleotide analogs Drug: nucleotide analogs Once/day, 1 capsule/time, oral	Drug: Nucleotide analogs; Once/day, 1 capsule/time, oral; Other Names: Entecavir; Tenofovir disoproxil fumarate; Tenofovir alafenamide fumarate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum HBsAg	Serum HBsAg level	24 weeks after the treatment
Serum HBsAg	Serum HBsAg level	48 weeks after the treatment
Serum HBsAg	Serum HBsAg level	24 weeks after the end of treatment
Serum HBV DNA	Serum HBV DNA level	Baseline
Serum HBV DNA	Serum HBV DNA level	24 weeks after the treatment
Serum HBV DNA	Serum HBV DNA level	48 weeks after the treatment
Serum HBV DNA	Serum HBV DNA level	24 weeks after the end of treatment
Serum alanine aminotransferase (ALT)	Serum ALT level	Baseline
Serum alanine aminotransferase (ALT)	Serum ALT level	24 weeks after the treatment
Serum alanine aminotransferase (ALT)	Serum ALT level	48 weeks after the treatment
Serum alanine aminotransferase (ALT)	Serum ALT level	24 weeks after the end of treatment
Serum Hepatitis B surface antigen (HBsAg) level	Serum HBsAg level	Baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune response of T, B, NK and myeloid cells	Frequencies and functions of T, B, NK and myeloid cells (tested by flowcytometry/FluoroSpot/ELISPOT)	Baseline
Immune response of T, B, NK and myeloid cells	Frequencies and functions of T, B, NK and myeloid cells (tested by flowcytometry/FluoroSpot/ELISPOT)	24 weeks after the treatment
Immune response of T, B, NK and myeloid cells	Frequencies and functions of T, B, NK and myeloid cells (tested by flowcytometry/FluoroSpot/ELISPOT)	48 weeks after the treatment
Immune response of T, B, NK and myeloid cells	Frequencies and functions of T, B, NK and myeloid cells (tested by flowcytometry/FluoroSpot/ELISPOT)	24 weeks after the end of treatment
Virus and host genome	Detect virus and host genome (focusing on HBV genotype, resistant mutation) using peripheral blood by sequencing	Baseline
Other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)	Levels of other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)	24 weeks after the treatment
Other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)	Levels of other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)	48 weeks after the treatment
Other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)	Levels of other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)	24 weeks after the end of treatment
Other HBV markers: Hepatitis B surface antibody (HBsAb), Hepatitis B e antigen (HBeAg), Hepatitis B e antibody (HBeAb), and Hepatitis B core antibody (HBcAb).	Levels of other HBV markers (HBsAb, HBeAg, HBeAb, and HBcAb)	Baseline

Collaborators and Investigators

• Sponsor: The Second Affiliated Hospital of Chongqing Medical University
• Collaborators: Guizhou Provincial People's Hospital; First Affiliated Hospital of Chongqing Medical University; Three Gorges Hospital of Chongqing University
• Investigators: Study Director: Hong Ren, MM, The Second Affiliated Hospital of Chongqing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: April 29, 2026
• First Submitted That Met QC Criteria: May 5, 2026
• First Posted (Actual): May 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: July 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis, Chronic; Hepatitis; Pathological Conditions, Signs and Symptoms; Hepatitis B; Hepatitis B, Chronic; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Purines; Organophosphorus Compounds; Organophosphonates; Adenine; Tenofovir; entecavir
• Other Study ID Numbers: 20231223

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No