Chronic Hepatitis B
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGSintilimab
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.
DRUGPegylated Interferon-α 2b
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.
Sponsors
Beijing 302 Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* 1\. Aged 18-55 years; * 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.Patients with HBV DNA negative, HBeAg negative, HBsAg quantification ≤ 500IU/ml .
Exclusion criteria
* 1\. Cirrhosis; * 2.platelet count \< 90×10\^9/L, WBC count \< 3.0×10\^9/L, ALT /AST\> ULN (40U/L), total bilirubin \> 2ULN; * 3.History of or suspicion of hepatocellular carcinoma * 4.Patients received interferon therapy within 6 months; * 5.Patients received immunosuppressive therapy or other therapy influenced study within 6 months; * 6.Pregnancy * 7.Hepatitis A, hepatitis C, hepatitis D, HIV infection or other active infections; * 8.Presence of severe uncontrolled diseases of respiratory, cardiovascular or other organ systems; * 9.Alcohol or drug abuse/dependence; * 10.Other conditions rendering subjects ineligible for enrollment, including but not limited to absolute contraindications to interferon therapy, known hypersensitivity to any study drug or their excipients, and anticipated poor compliance with treatment and follow-up procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The rate of patients with HBsAg loss at Weeks 24 and 48 | 48weeks |
| Incidence of treatment-emergent adverse events/serious adverse events | 48weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The rate of patients with HBsAg decline > 1log(IU/ml) at Weeks 24 and 48 | 48 weeks | — |
| The rate of patients with HBsAb positive at Weeks 24 and 48. | 48 weeks | — |
| The concentration of HBcrAg at baseline, at weeks 12, 24 and 48. | 48 weeks | Evaluate the level of serum HBcrAg at baseline, at weeks 12,24 and 48. |
| The concentration of pgRNA at baseline, at weeks 12,24 and 48. | 48 weeks | Evaluate the level of serum pgRNA at baseline, at weeks 12,24 and 48. |
| The concentration of anti-HBc at baseline, at weeks 12,24 and 48. | 48 weeks | Evaluate the level of serum anti-HBc at baseline, at weeks 12,24 and 48. |
| Frequency and function of peripheral T-lymphocytes assessed by flow cytometry, FluoroSpot and ELISpot, at weeks 12,24 and 48. | 48 weeks | The frequency (unit: percentage of peripheral lymphocytes) and function of peripheral T-lymphocytes will be evaluated using flow cytometry, FluoroSpot, and ELISpot assays. |
| Frequency and function of peripheral B-lymphocytes assessed by flow cytometry, FluoroSpot and ELISpot,at weeks 12,24 and 48. | 48 Weeks | The frequency (unit: percentage of peripheral lymphocytes) and function of peripheral B-lymphocytes will be evaluated using flow cytometry, FluoroSpot, and ELISpot assays. |
| Frequency and function of peripheral NK-lymphocytes assessed by flow cytometry, FluoroSpot and ELISpot at weeks 12,24 and 48. | 48 weeks | The frequency (unit: percentage of peripheral lymphocytes) and function of peripheral NK-lymphocytes will be evaluated using flow cytometry. |
Countries
China
Contacts
CONTACTJunliang Fu
PRINCIPAL_INVESTIGATORJunliang Fu
Beijing 302 Hospital
Outcome results
None listed