The Treatment of PD-1 Antibody Combined With Peg-IFNα in NAs-suppressed CHB Patients

The Safety and Efficacy of PD-1 Antibody Combined With Pegylated Interferon-α Therapy to Promote the Clinical Cure in Nucleoside (Acid) Analogues-suppressed Chronic Hepatitis B Patients: A Protocol for the Prospective Pilot Study

This is a prospective, open-labled, randomized controlled study to assess efficacy and safety of treatment with Sintilimab (PD-1 antibody) combined Peg-IFNα-2b in CHB patients on stable NAs treatment.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Peg-IFNα-2b; Drug: NAs; Drug: Sintilimab

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100039
      • the Fifth Medical Center, Chinese PLA General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 18 - 65 years old;
2. Chronic hepatitis B patients with clear diagnosis of hematology, etiology and clinical (for example: HBsAg positive for more than 6 months);
3. Treatment with NAs (ETV, TDF or TAF）at least 1 years and continue NAs therapy during screening;
4. HBV DNA and HBeAg turn negative after NAs treatment;
5. HBsAg ranged 200-1000 IU/ml.

Exclusion Criteria:

1. Cirrhosis;
2. platelet count < 90×10^9/L, WBC count < 3.0×10^9/L, neutrophil count < 1.3×10^9/L, ALT > ULN（40U/L）, total bilirubin > 2ULN;
3. History of or suspicion of hepatocellular carcinoma
4. Patients received interferon therapy within 12 months;
5. Patients received immunosuppressive therapy or other therapy influenced study within 12 months;
6. Hepatitis A, hepatitis C, hepatitis D, HIV infection or other active infections;
7. Alcohol or drug abuse/dependence;
8. Investigator judges that the participants are not suitable for this 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Peg-IFNα group; 180 ug Peg-IFNα-2b subcutaneous injection once/week for 48 weeks NAs	Drug: Peg-IFNα-2b; 180ug/0.5ml/1bottle; Drug: NAs; tablets; Other Names: ETV/TDF/TAF
Active Comparator: PD-1 antibody group; 1.5 mg/kg Sintilimab intravenous injection once per 3 weeks for 24 weeks NAs	Drug: NAs; tablets; Other Names: ETV/TDF/TAF; Drug: Sintilimab; 100mg/10ml/1bottle
Experimental: PD-1 antibody combined Peg-IFNα group; 1.5 mg/kg Sintilimab intravenous injection once per 3 weeks for 24 weeks 180 ug Peg-IFNα-2b subcutaneous injection once/week for 48 weeks NAs	Drug: Peg-IFNα-2b; 180ug/0.5ml/1bottle; Drug: NAs; tablets; Other Names: ETV/TDF/TAF; Drug: Sintilimab; 100mg/10ml/1bottle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of HBsAg loss at 24 weeks and 48 weeks.	Evaluate the level of HBsAg at 24 weeks and 48 weeks.	48 weeks
Incidence of treatment-emergent adverse events/serious adverse events	Evaluate the treatment-emergent adverse events/serious adverse events	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The rate of HBsAg decline > 1log(IU/ml) at 24 weeks and 48 weeks	Evaluate the level of serum HBsAg at 24 weeks and 48 weeks.	48 weeks
The rate of HBsAb positive at 24 weeks and 48 weeks.	Evaluate the level of serum HBsAb at 24 weeks and 48 weeks.	48 weeks
The concentration of HBcrAg at baseline, 12 weeks, 24 weeks and 48 weeks.	Evaluate the level of serum HBcrAg at baseline, 12 weeks, 24 weeks and 48 weeks.	48 weeks
The concentration of pgRNA at baseline, 12 weeks, 24 weeks and 48 weeks.	Evaluate the level of serum pgRNA at baseline, 12 weeks, 24 weeks and 48 weeks.	48 weeks
The concentration of anti-HBc at baseline, 12 weeks, 24 weeks and 48 weeks.	Evaluate the level of serum anti-HBc at baseline, 12 weeks, 24 weeks and 48 weeks.	48 weeks
Immune response of T cell, B cell, NK cell at baseline, 12 weeks, 24 weeks and 48 weeks.	Evaluate the frequency and function of T cell, B cell, NK cell (tested by flowcytometry/fluorospot/elispot)	48 weeks

Collaborators and Investigators

• Sponsor: Beijing 302 Hospital

Publications and helpful links

General Publications

• Wang H, Li X, Lu J, Zhang X, Dang S, Li Y, He Y, Guo Y, Wang J, Maimaitijiang W, Zheng S, Ren S, Cao H, Zhang W, Zhang X, Ma H, Wang FS, Fu J. Safety and efficacy of PD-1 antibody combined with pegylated interferon alpha for functional cure in nucleos(t)ide analogues-suppressed chronic hepatitis B patients: protocol for a multicentre randomised controlled trial. BMJ Open. 2025 Sep 21;15(9):e105710. doi: 10.1136/bmjopen-2025-105710.

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2024
• Primary Completion (Estimated): October 8, 2026
• Study Completion (Estimated): October 8, 2026

Study Registration Dates

• First Submitted: March 20, 2024
• First Submitted That Met QC Criteria: April 9, 2024
• First Posted (Actual): April 10, 2024

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: October 1, 2025

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; Anti-Infective Agents; Antiviral Agents; sintilimab; nas
• Other Study ID Numbers: PIN-CHB-1

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