Sequential Combination Therapy With PD-1 Antibody and Peg-IFNα in CHB Patients

The Safety and Efficacy of Sequential Combination Therapy With PD-1 Antibody and Pegylated Interferon-α in NA-supressed Chronic Hepatitis B Patients

This is a prospective study to evaluate the safety and efficacy of Sintilimab (PD-1 antibody) in sequential combination with Peg-IFNα-2b in NA-supressed CHB patients who had previously received Peg-IFNα therapy.

Study Overview

• Status: Recruiting
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Peg-IFNα-2b; Drug: NAs; Drug: Sintilimab

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • the Fifth Medical Center, Chinese PLA General Hospital
      • Contact: Junliang Fu; Phone Number: 86-10-66933214; Email: fjunliang@163.com
      • Contact: Fu-Sheng Wang; Phone Number: +861066933328; Email: fswang302@163.com

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. In virologically suppressed (HBV DNA below the lower detection limit) CHB patients by NAs treatment, HBsAg decreased by less than 0.5log in the last 6 months of Peg-IFNα therapy, and then discontinued Peg-IFNα at least 6 months;
• 4.Patients with HBV DNA negative, HBeAg negative, HBsAg quantification ≤ 200IU/ml at Peg-IFNα discontinuation and enrollment.

Exclusion Criteria:

• 1. Cirrhosis;
• 2.platelet count < 90×109/L, WBC count < 3.0×109/L, neutrophil count < 1.3×109/L, ALT > ULN (40U/L), total bilirubin > 2ULN;
• 3.History of or suspicion of hepatocellular carcinoma
• 4.Patients received immunosuppressive therapy or other therapy influenced study within 12 months;
• 5.Hepatitis A, hepatitis C, hepatitis D, HIV infection or other active infections;
• 6.Alcohol or drug abuse/dependence;
• 7.Investigator judges that the participants are not suitable for this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PD-1 antibody therapy	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
Incidence of treatment-emergent adverse events/serious adverse events	Evaluate the treatment-emergent adverse events/serious adverse events	48 weeks
The rate of HBsAg loss (<0.05 IU/ml) at 24 weeks and 48 weeks	Evaluate the level of HBsAg (IU/ml) at 24 weeks and 48 weeks.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
The rate of HBsAg decline > 1log(IU/ml) at 24 weeks and 48 weeks	Evaluate the level of serum HBsAg (IU/ml) at 24 weeks and 48 weeks.	48 weeks
The rate of HBsAb positive (>10 IU/ml) at 24 weeks and 48 weeks.	The rate of HBsAb positive (>10 IU/ml) at 24 weeks and 48 weeks.	48 weeks
The concentration of HBcrAg (logU/mL) at baseline, 12 weeks, 24 weeks and 48 weeks	Evaluate the level of serum HBcrAg (logU/mL) at baseline, 12 weeks, 24 weeks and 48 weeks.	48 weeks
The concentration of pgRNA (>10 IU/ml) at baseline, 12 weeks, 24 weeks and 48 weeks	Evaluate the level of serum pgRNA (>10 IU/ml) at baseline, 12 weeks, 24 weeks and 48 weeks	48 weeks
The concentration of anti-HBc (IU/ml) at baseline, 12 weeks, 24 weeks and 48 weeks	Evaluate the level of serum anti-HBc (IU/ml) at baseline, 12 weeks, 24 weeks and 48 weeks	48 weeks

Collaborators and Investigators

• Sponsor: Beijing 302 Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2024
• Primary Completion (Estimated): December 15, 2025
• Study Completion (Estimated): December 15, 2025

Study Registration Dates

• First Submitted: June 10, 2024
• First Submitted That Met QC Criteria: June 10, 2024
• First Posted (Actual): June 13, 2024

Study Record Updates

• Last Update Posted (Actual): June 20, 2024
• Last Update Submitted That Met QC Criteria: June 17, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis B, Chronic; Hepatitis, Chronic; Anti-Infective Agents; Antiviral Agents; Peginterferon alfa-2b
• Other Study ID Numbers: PIN-CHB-2

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