Efficacy of NA Combined With PEG-IFN-α2b in the Continuous Versus Pulsed Treatment of Patients With Chronic Hepatitis B

NCT05922306 | Recruiting Early Phase 1 DMC

• 1 other identifier: LCYJ2021ZD006
• Study Type: interventional
• Target: 1,084
• Locations: 1 country
• Sites: 1

Brief Summary

Previous studies have shown that there are alterations in the number and affinity of interferon receptors during interferon therapy and that such alterations recover to varying degrees some time after the end of treatment. It can be conjectured that the rest period of pulsed therapy facilitates the recovery of type I interferon receptors and thus the next round of IFN therapy compared to a continuous regimen of interferon.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (2)

• HBsAg negative conversion rate after 96 weeks of treatment

  After 96 weeks of treatment, 5 ml of blood will be drawn from the patient, serum will be extracted, and HBsAg values will be quantified by chemiluminescence assay; samples less than 0.5 ng/ml will be judged as negative.

  96 weeks

• HBsAb conversion rate after 96 weeks of treatment

  After 96 weeks of treatment, 5 ml of blood will be drawn from the patient, serum will be extracted, and HBsAb values will be quantified by chemiluminescence; samples greater than 10 miu/ml 0.5 will be judged as positive.

  96 weeks

Study Arms (2)

Continuous Combination Therapy Cohort

ACTIVE COMPARATOR

Patients with primary CHB with HBsAg ≥ 1500 IU/ml and HBV-DNA \< 500 IU/ml and patients with CHB after treatment with NAs will be enrolled. After fully informed consent, pegylated interferon alpha-2b 180µg will be administered by subcutaneous injection once a week for up to 96 weeks.

Drug: PEGylated recombinant human interferon alpha-2b injection

Pulsed Combination Therapy Cohort

EXPERIMENTAL

Patients with primary CHB with HBsAg ≥ 1500 IU/ml and HBV-DNA \< 500 IU/ml and patients with CHB after treatment with NAs will be enrolled. After fully informed consent, pegylated interferon alpha-2b 180µg will be administered by subcutaneous injection once weekly for 8 weeks of treatment and discontinued for 4 weeks up to 96 weeks.

Drug: PEGylated recombinant human interferon alpha-2b injection

Interventions

PEGylated recombinant human interferon alpha-2b injection DRUG

Continuous combination therapy: pegylated interferon alpha-2b 180µg, subcutaneously once a week for 96 weeks, combined with NAs throughout the treatment period.

Also known as: Nucleotide analogues

Continuous Combination Therapy Cohort

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 to 60 years, both sexes (both 18 and 60 years)
• HBsAg positive for more than 6 months;
• NAs treated patients on continuous NA therapy for more than 6 months with HBsAg ≥ 1500 IU/ml and HBV-DNA \< 500 IU/ml at enrolment;
• Primary treated patients with surface antigen \>1500 IU, unlimited E antigen and unlimited HBV DNA at enrolment, meeting the treatment indications of the 2019 edition of the guidelines for the prevention and treatment of chronic hepatitis B.
• negative urine or serum pregnancy test within 24 hours prior to the first dose (for women of childbearing age)

You may not qualify if:

• Combined active hepatitis A, C, D, E and/or HIV infection;
• Patients who are on future and intend to continue to use tibivudine
• methaemoglobin greater than 100ng/ml at screening; or methaemoglobin that has not remained stable for 3 months prior to the trial and/or liver imaging suggestive of liver tumours;
• decompensated liver disease (Child-Pugh score ≥ 7), meaning that patients will be excluded if one of the following is met: prolonged prothrombin time ≥ 3 seconds, serum bilirubin \> 34umol/L, history of hepatic encephalopathy, history of oesophageal variceal bleeding, ascites;
• pregnant or lactating women or patients with planned pregnancy during the study period and unwilling to use contraception
• Neutrophil count \< 1.5 x 10\^9/L or platelet count \< 90 x 10\^9/L and creatinine \> 1.5 ULN
• History of severe psychiatric illness, especially depression. Major psychosis defined as major depressive disorder or psychosis, suicide attempts, hospitalisation for psychosis or incapacity for a period of time due to psychosis;
• history of immune-mediated disease (e.g. inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anaemia, scleroderma, severe psoriasis, rheumatoid arthritis) or abnormally elevated levels of autoimmune antibodies
• Patients with severe combined diseases of the heart, lungs, kidneys, brain, blood and other vital organs, combined with other malignancies
• History of severe epilepsy or current treatment with anti-epileptic drugs. Unstable control of diabetes mellitus, hypertension, thyroid disease, etc. Patients with a history of severe retinopathy or as indicated by other evidence of retinopathy;
• History of any organ transplantation and existing functional grafts (except corneal or hair transplants);
• Patients who are allergic to interferon and its drug components and who, in the judgment of the investigator, are unsuitable for interferon application
• Patients who, in the opinion of the investigator, are not suitable for participation in this study.

Sponsors & Collaborators

• Anhui Medical University: lead
• The First Affiliated Hospital, University of Science and Technology of China: collaborator
• The Second Hospital of Anhui Medical University: collaborator
• Chaohu Hospital of Anhui Medical University: collaborator
• The First Affiliated Hospital of Bengbu Medical University: collaborator

Study Sites (1)

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 23000, China

RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jiabing Li, MD

  The First Affiliated Hospital of Anhui Medical University

  STUDY CHAIR

Central Study Contacts

Yufeng Gao, MD

CONTACT

13956938032; aygyf@anmu.edu.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Participants and investigators will be informed of the treatment protocol. Participants will be grouped according to the random number method at initial entry and will be given the option to continue in the current cohort or withdraw from the cohort study at their own discretion after treatment assessment at each node.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: June 2, 2023
• First Posted: June 28, 2023
• Study Start: July 1, 2023
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 28, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)