Efficacy and Safety Study of Peginterferon Alfacon-2 to Treat Chronic Hepatitis B Virus Infection

Current clinical practices has shown promising prospects of the therapy strategy of interferon combined with nucleos(t)ides in patients with chronic hepatitis B, but the safety and efficacy has not been fully studied. This study is aimed to exploit the safety and efficacy of the study drug, Peginterferon Alfacon-2 injection, with nucleos(t)ide (NAs), Tenofovir alafenamide Fumarate Tablets (TAF), in the patients with hepatitis B virus infection.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B Virus Infection
• Intervention / Treatment: Drug: Peginterferon Alfacon-2; Drug: Peginterferon Alfacon-2 placebo

• Study Type: Interventional
• Enrollment (Actual): 336
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Ditan Hospital, Capital Medical University
  • Beijing, China
    • Beijing Youan Hospital, Capital Medical University
  • Beijing, China
    • Peking university Peoole's hospital
  • Changchun, China
    • The First Hospital of Jilin University
  • Changsha, China
    • Xiangya Hospital Central South University
  • Changsha, China
    • The Second Xiangya Hospital of Central South University
  • Chengdu, China
    • Sichuan Provincial People's Hospital
  • Chizhou, China
    • The Peoole's hospital of Chizhou
  • Chongqing, China
    • The Second Affiliated Hospital of Chongqing Medical University
  • Chongqing, China
    • The First Affiliated Hospital of Army Medical University
  • Fuzhou, China
    • The First Affiliated Hospital Of Fujian Medical University
  • Fuzhou, China
    • Mengchao Hepatobiliary Hospital Of Fujian Medical University
  • Guangzhou, China
    • Guangzhou Eighth People's Hospital
  • Harbin, China
    • The Fourth Affiliated Hospital of Harbin Medical University
  • Heze, China
    • Heze Municipal Hospital
  • Jinan, China
    • Shandong Public Health Clinical Center
  • Langfang, China
    • Hebei Petro China Central Hospital
  • Nanchang, China
    • The First Affiliated Hospital of Nanchang University
  • Nanjing, China
    • The Second Hospital of Nanjing
  • Pingxiang, China
    • Pingxiang No.2 People's Hospital
  • Qingdao, China
    • Qingdao Municipal Hospital
  • Qingyuan, China
    • The Peoole's hospital of Qingyuan
  • Shenyang, China
    • The Sixth People's Hospital of Shenyang
  • Shijiazhuang, China
    • The Third Hospital of Hebei Medical University
  • Shijiazhuang, China
    • Shijiazhuang Hospital of Traditional Chinese Medicine
  • Tianjin, China
    • Tianjin Third Central Hospital
  • Tianjin, China
    • The Second People's Hospital of Tianjin
  • Wuhan, China
    • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • Wuhan, China
    • TongJi Medical College of HUST
  • Xi'an, China
    • The Second Affiliated Hospital of Xian Jiaotong University
  • Xingxiang, China
    • The third affiliated hospital of Xingxiang medical university
  • Yanbian, China
    • Yanbian University Hospital
  • Zhengzhou, China
    • Henan People's Hospital
  • Zhengzhou, China
    • The Sixth People's Hospital of Zhengzhou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age between 18 and 65 years (including 18 and 60), no gender limit.
• BMI between 18 and 30 kg/m2 (including 18 and 30).
• For treatment naive patients: Did not receive standard anti-HBV treatment within 6 months prior to screening (Including interferon, NAs, and other anti-HBV drugs).
• For NAs treated patients: Who should have continuously taken NAs for at least 9 months prior to screening, and are currently receiving the NAs.
• HBsAg positive for at least 6 months and HBsAg between 10 and 1000 IU/mL (excluding 10 and 1000).
• HBsAb and HBeAg both are negative at screening.
• For treatment naive patients: HBV DNA < 2×10^3 IU/mL at screening.
• For NAs treated patients: HBV DNA < 100 IU/mL at screening.
• For treatment naive patients: ALT ≤ 5ULN at screening.
• For NAs treated patients: ALT ≤ 2ULN at screening.
• Liver stiffness measurement <8.0 kPa at screening.
• Pregnancy test of female of childbearing must be negative at screening, and the subjects (male and female) should take effective contraceptive measures during the whole study period.
• Understand and sign the informed consent form voluntarily.

Exclusion Criteria:

• For NAs treated patients: who have received standard treatment of interferon products within 6 months prior to screening.
• Systemic therapy with potent immunomodulatory agents such as adrenocorticotropic hormone, thymosin α1, etc more than two weeks within past 6 months, not including corticosteroid nasal sprays, inhaled steroids and / or topical steroids.
• Co-infected with Hepatitis A, Hepatitis C, Hepatitis D, Hepatitis E, or HIV.
• Evidence of liver compensation, including previous liver biopsy, imaging examination or clinical manifestations.
• Evidences of hepatic decompensation, including but not limited to serum total bilirubin> 2 times the upper limit of normal (ULN); serum albumin <35g/L; prothrombin activity (PTA) <60%; ascites, upper gastrointestinal bleeding and hepatic encephalopathy; Child-Pugh score B/C grade.
• Evidence of hepatocellular carcinoma, or AFP>>50 ng/mL, or imaging examination revealed suspicious nodules in the liver.
• Liver diseases from other causes, including alcoholic liver disease, non-alcoholic steatohepatitis, drug-induced hepatitis, autoimmune hepatitis (antinuclear antibody titer higher than 1:100), hepatolenticular degeneration (Wilson's disease) and hemochromatosis, etc.
• White blood cell count <3×10^9/L; neutrophil count<1.5×10^9/L; platelet count<90×10^9/L; hemoglobin below the lower limit of normal; serum creatine kinase (CK) >3×ULN; blood phosphorus <0.8 mmol/L; serum creatinine (SCr) > 1×ULN.
• Diabetes mellitus or Poorly controlled Thyroid Diseases.
• Poorly controlled hypertension (systolic blood pressure> 140mmHg, or diastolic blood pressure> 90 mmHg) with hypertension -related retinal lesions.
• Immunodeficiency or autoimmune diseases including but not limited to inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, scleroderma, Sjogren's syndrome, autoimmune thrombocytopenia, etc.
• Psychiatric and nervous system disorders, including history of psychiatric illness or with family history (especially depression, depressive tendencies, epilepsy and hysteria, etc.)
• Severe cardiovascular diseases (New York Heart Association functional class (NYHA) Ⅲ level and above, myocardial infarction occurred within past 6 months or PTCA performed within past 6 months, unstable angina, uncontrolled arrhythmias).
• Serious blood disorders (all kinds of anemia, hemophilia, etc.)
• Severe kidney disease (chronic kidney disease, renal insufficiency, etc.)
• Serious digestive diseases (gastrointestinal ulcers, colitis, etc.)
• Severe respiratory disease (pneumonia, chronic obstructive pulmonary disease, interstitial lung disease, etc.)
• Retinal disease (retinal exfoliation, macular hole, retinal tumors, etc.)
• Malignancies.
• Function organs transplant.
• Allergies or severe allergies, especially allergic to study drugs or any ingredients of the study drugs.
• Evidence of alcohol or drug abuse (average alcohol consumption male> 40g / day, female> 20g / day).
• Women who are pregnant or lactating or to be pregnant during the study period.
• Participated in other clinical trials 3 months prior to the screening.
• Unwilling to sign the informed consent and adhere to treatment requirements.
• Other conditions not suitable for study judged by investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Peginterferon Alfacon-2 treated patients	Drug: Peginterferon Alfacon-2; Peginterferon Alfacon-2 injection will be weekly subcutaneous injected for 48 weeks. Tenofovir alafenamide Fumarate Tablets(TAF) will be take orally for at least 48 weeks, not more than 72 weeks. Peg-interferon Alfacon-2 and TAF will discontinue when HBsAg levels is less than 0.05 IU/mL and HBV DNA is below 10 IU/mL during 48-72 weeks.
Placebo Comparator: Peginterferon Alfacon-2 placebo treated patients	Drug: Peginterferon Alfacon-2 placebo; Peginterferon Alfacon-2 placebo injection will be weekly subcutaneous injected for 48 weeks. Tenofovir alafenamide Fumarate Tablets(TAF) will be take orally for at least 48 weeks, not more than 72 weeks. Peg-interferon Alfacon-2 and TAF will discontinue when HBsAg levels is less than 0.05 IU/mL and HBV DNA is below 10 IU/mL during 48-72 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with HBsAg negative.	Percentage of Participants with HBsAg <0.05 IU/mL	72 weeks

Collaborators and Investigators

• Sponsor: Beijing Kawin Technology Share-Holding Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2021
• Primary Completion (Actual): November 30, 2023
• Study Completion (Actual): December 30, 2023

Study Registration Dates

• First Submitted: July 30, 2024
• First Submitted That Met QC Criteria: August 5, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): August 9, 2024
• Last Update Submitted That Met QC Criteria: August 5, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Blood-Borne Infections; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Chronic Disease; Infections; Communicable Diseases; Hepatitis B; Hepatitis; Hepatitis A; Virus Diseases; Hepatitis B, Chronic; Hepatitis, Chronic; Herpesviridae Infections
• Other Study ID Numbers: Kawin-2021-001

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