Pegylated Interferon α in Previously Interferon-treated CHB（Leading Study）

Official title

A Prospective, Multicenter, Non-randomized, Controlled Study to Pursuit Clinical Functional Cure of Pegylated Interferon α in Previously Interferon-treated Chronic Hepatitis B （Leading Study）

Overview

Previous clinical practice and exploratory studies suggest that some patients who have not achieved functional cure in the first round of interferon therapy can achieve HBsAg clearance by interferon retreatment (intermittent therapy), which can reduce the occurrence of complications such as liver fibrosis, liver cirrhosis and liver cancer, and its clinical benefit is expected to be higher than that of NAs monotherapy. This study is aimed to conduct a large-scale, multicenter, prospective study to confirm the benefit of peginterferon-based therapies in these populations. It expected to enroll about 2000 patients with chronic hepatitis B who have received prior interferon therapy and achieved a good response but without function cure, patients receive either interferon-based therapy or NAs monotherapy, according to their wishes and doctors' professional recommendations, with a ratio of 2:1 between the two groups, and all patients treated for 48 weeks. The HBsAg clearance rate before and after treatment, safety, etc. will be analyzed.

Interventions

• Drug Peginterferon α-2b based treatment group
  Peginterferon α-2b injection, 180mcg, s.c, once a week, for 48 weeks. If the baseline HBV DNA is higher than the minimum detection limit (using high-sensitivity kit), combined with nucleos(t)ide analogs (NAs) is recommended.
• Drug NAs monotherapy group
  First-line NAs (e.g. Entecavir (ETV), tenofovir disoproxil fumarate (TDF), tenofovir alafenamide fumarate (TAF), tenofovir amibufenamide (TMF)), one tablet a day, take orally, for 48 weeks.

Primary outcome measures

• Proportion of patients with HBsAg below the lower limit of detection. [Time frame: Week 48]

Secondary outcome measures (7)

• Decrease of HBV DNA levels at week 48 compared to baseline. [Time frame: Week 48]
• Proportion of patients with HBV DNA below the lower limit of detection. [Time frame: Week 48]
• Decrease of HBsAg levels at week 48 compared to baseline. [Time frame: Week 48]
• Proportion of patients with HBsAg seroconversion. [Time frame: Week 48]
• Proportion of patients with HBeAg below the lower limit of detection for patients with baseline HBeAg positive. [Time frame: Week 48]
• Proportion of patients with HBeAg seroconversion for patients with baseline HBeAg positive. [Time frame: Week 48]
• Serious adverse events. [Time frame: from baseline to 48 weeks.]

Eligibility criteria

Inclusion criteria

• Understand and sign the informed consent, participate in the study voluntarily.
• Aged between 18 and 65 (including 18 and 65).
• HBsAg positive for at least 6 months or other evidence suggests chronic hepatitis B.
• Had previously received interferon therapy, and discontinuation for at least 6 months at the time of enrollment, with a HBsAg level declined for at least 80% at the end of interferon treatment compared to the level of treatment started.
• HBsAg≤500 IU/mL at screening, and HBsAg rebound should not exceed 50% when compared to the HBsAg level of previously interferon treatment started.
• The pregnancy test within 24 hours previous to the first medication must be negative for women of childbearing. And all participants (male and female) should use effective contraception during the study period.

Exclusion criteria

• Pregnant or lactating women, or those who had a birth plan during the study period.
• Patients with neuropsychiatric disorders, especially depression, anxiety, mania, schizophrenia and other mental illness history or family history of mental illness.
• Patients with chronic liver disease caused by hepatitis A, hepatitis C, hepatitis E and/or HIV infection, or other causes (such as alcoholic hepatitis, drug-induced hepatitis, autoimmune liver disease, etc.).
• Evidence of acute severe liver damage: ALT>10 ULN, or markedly elevated ALT with significantly elevated bilirubin.
• Evidence of uncompensated liver disease: ascites, esophageal and gastric varices rupture bleeding, sepsis, hepatic encephalopathy, hepatorenal syndrome, etc. Or previous evidence of decompensation of cirrhosis.
• Patients with evidence of hepatocellular carcinoma or AFP>1 ULN.
• Kidney diseases: acute or chronic nephritis, renal insufficiency, nephrotic syndrome, etc. Or serum creatinine >1 ULN at screening.
• Neutrophil count <1.5×10\^9/L, platelet count <90×10\^9/L, blood phosphorus < 0.8 mmol /L.
• Autoimmune diseases (such as psoriasis, systemic erythematosus, etc.), endocrine system diseases (such as thyroid diseases, diabetes, etc.), hypertension (blood pressure ≥140/90 mmHg) poorly controlled by prescription drugs, serious history of heart disease (especially in the past 6 months), severe retinopathy or other serious eye diseases. Patients with organic disease or dysfunction of other vital organs.
• Patients who plan to receive organ transplant or have already undergone organ transplant.
• Patients who allergic to the investigational drug or any of its excipients, or who meet any contraindication declared in the instructions of the investigational drug.
• Other conditions that are considered inappropriate for enrollment by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Department of Infectious Diseases , Ruijin Hospital, Shanghai Jiao Tong University School — Shanghai

Identifiers

NCT: NCT06323681 · Leading Study

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗