This is a prospective, multicenter, randomized, open-label controlled clinical trial designed to evaluate the efficacy and safety of a sequential treatment strategy incorporating a PD-1 antibody and pegylated interferon-α (Peg-IFNα) in patients with chronic hepatitis B receiving stable nucleos(t)ide analogue (NA) therapy.
A total of 60 participants will be randomly assigned in a 1:1 ratio to an experimental group or a control group. Participants in the experimental group will initially receive a PD-1 antibody in combination with continued NA therapy, followed by a period of triple therapy with the PD-1 antibody, Peg-IFNα, and NAs. The PD-1 antibody will then be discontinued, while Peg-IFNα plus NAs will be continued through Week 48. Participants in the control group will receive Peg-IFNα plus continued NA therapy from baseline through Week 48.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Sintilimab will be administered intravenously at a dose of 1.0 mg/kg at Weeks 0, 6, 12, and 18, for a total of four doses.
Peg-IFNα will be administered subcutaneously once weekly from Week 12 through Week 48. Dose: 135 μg or 180 μg, according to the study protocol. When sintilimab and Peg-IFNα are scheduled during the same treatment period, administration of the two drugs will be separated by at least 72 hours.
Background nucleos(t)ide analogue therapy with entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide will be continued throughout the study.
Shandong Public Health Clinical Center
Jinan, China
The Third People's Hospital of Taiyuan
Taiyuan, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, China
The Second Affiliated Hospital of Xi'an Jiaotong University
Xi'an, China
The rate of patients with HBsAg loss at Weeks 24 and 48
Time frame: 48weeks
Incidence of treatment-emergent adverse events/serious adverse events
Time frame: 48weeks
The rate of patients with HBsAg decline > 1log(IU/ml) at Weeks 24 and 48
Time frame: 48 weeks
The rate of patients with HBsAb positive at Weeks 24 and 48.
Time frame: 48 weeks
The concentration of HBcrAg at baseline, at weeks 12, 24 and 48.
Evaluate the level of serum HBcrAg at baseline, at weeks 12,24 and 48.
Time frame: 48 weeks
The concentration of pgRNA at baseline, at weeks 12,24 and 48.
Evaluate the level of serum pgRNA at baseline, at weeks 12,24 and 48.
Time frame: 48 weeks
The concentration of anti-HBc at baseline, at weeks 12,24 and 48.
Evaluate the level of serum anti-HBc at baseline, at weeks 12,24 and 48.
Time frame: 48 weeks
Frequency and function of peripheral T-lymphocytes assessed by flow cytometry, FluoroSpot and ELISpot, at weeks 12,24 and 48.
The frequency (unit: percentage of peripheral lymphocytes) and function of peripheral T-lymphocytes will be evaluated using flow cytometry, FluoroSpot, and ELISpot assays.
Time frame: 48 weeks
Frequency and function of peripheral B-lymphocytes assessed by flow cytometry, FluoroSpot and ELISpot,at weeks 12,24 and 48.
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Peg-IFNα will be administered subcutaneously once weekly from Week 0 through Week 48. Dose: 135 μg or 180 μg, according to the study protocol.
Background nucleos(t)ide analogue therapy with entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide will be continued throughout the study.
The frequency (unit: percentage of peripheral lymphocytes) and function of peripheral B-lymphocytes will be evaluated using flow cytometry, FluoroSpot, and ELISpot assays.
Time frame: 48 Weeks
Frequency and function of peripheral NK-lymphocytes assessed by flow cytometry, FluoroSpot and ELISpot at weeks 12,24 and 48.
The frequency (unit: percentage of peripheral lymphocytes) and function of peripheral NK-lymphocytes will be evaluated using flow cytometry.
Time frame: 48 weeks