Combination Therapy of Pegylated Interferon Alfa-2a and Tenofovir Versus Tenofovir Monotherapy in Chronic Hepatitis B
HBRN
21 other identifiers
interventional
201
2 countries
21
Brief Summary
This clinical trial compares the efficacy of peginterferon plus tenofovir for 24 weeks followed by monotherapy with tenofovir for a further 3.5 years to the efficacy of tenofovir alone given for 4 years in patients with chronic hepatitis B. The primary measure of outcome will be HBsAg loss in serum at 48 weeks after stopping all antiviral therapy (sustained off-treatment response).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Nov 2012
Longer than P75 for phase_3
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 6, 2011
CompletedFirst Posted
Study publicly available on registry
June 8, 2011
CompletedStudy Start
First participant enrolled
November 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 8, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
March 8, 2021
CompletedResults Posted
Study results publicly available
October 12, 2022
CompletedApril 28, 2023
April 1, 2023
8.4 years
June 6, 2011
May 13, 2022
April 25, 2023
Conditions
Outcome Measures
Primary Outcomes (1)
Percent of Participants With Hepatitis B Surface Antigen (HBsAg) Loss by Week 240
Estimated percent of participants who became HBsAg negative by week 240 from randomization
Week 240
Secondary Outcomes (18)
Cumulative Percent of Participants With HBsAg Loss at Week 192
Week 192
Number of Participants With Serious Adverse Events
Up to 240 weeks
Number of Participants With Adverse Events
up to 240 weeks
Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 192
week 192
Number of Participants With HBeAg Loss at Week 240
week 240
- +13 more secondary outcomes
Study Arms (2)
Tenofovir
EXPERIMENTALTenofovir 192 weeks
Peginterferon-alfa 2a and tenofovir
EXPERIMENTALA combination of peginterferon-alfa 2a plus tenofovir for 24 weeks and then tenofovir only for 168 weeks
Interventions
A combination of peginterferon-alfa 2a 180 µg weekly plus tenofovir 300 mg daily for 24 weeks and then only tenofovir 300 mg daily for 168 weeks (3.5 years).
Eligibility Criteria
You may qualify if:
- Participant is enrolled in the HBRN Cohort Study (NCT01263587) or completed the necessary components of the cohort baseline evaluation by the end of the baseline visit for this study
- years or older
- Chronic hepatitis B infection as evidenced by at least one of the following:
- HBsAg positive result within 8 weeks prior to randomization and another time at least 24 weeks prior to randomization with no HBsAg negative result in between.
- HBsAg positive within 8 weeks prior to randomization and HBV DNA ≥1000 IU/mL on 2 occasions at least 24 weeks apart (can include result from screening visit within 8 weeks of randomization)
- Hepatitis B e antigen positive or negative
- Serum HBV DNA ≥1000 IU/mL on 2 occasions at least 4 weeks apart within the 32 weeks prior to randomization (can include result from screening visit within 8 weeks of randomization)
- At least 2 elevated serum alanine aminotransferase (ALT) levels (\> 30 U/L for males, \>20 U/L for females) 4 weeks apart, and no more than 32 weeks apart, with the second being within 8 weeks of randomization
- Compensated liver disease
- No evidence of hepatocellular carcinoma (HCC)
- Liver biopsy done that shows findings consistent with chronic hepatitis B with histology activity index (HAI) ≥3 (necroinflammatory component only) or Ishak fibrosis score ≥1 or both, as assessed by the local study pathologist on review of a liver biopsy done within 144 weeks of randomization
- Females of child bearing potential must agree to use an adequate method of contraception throughout the study and must have a negative pregnancy test immediately prior to the start of treatment
You may not qualify if:
- Serum ALT ≥450 U/L for males and ≥300 U/L for females
- Treatment with interferon or nucleos(t)ide analogues for hepatitis B within 48 weeks of randomization
- More than 48 weeks of therapy with nucleos(t)ide analogues for hepatitis B at any time in the past
- History of hepatic decompensation including but not limited to ascites, variceal bleeding, or hepatic encephalopathy
- Known allergy or intolerance to any of the study medications
- Females who are pregnant or breastfeeding
- Previous organ transplantation including engrafted bone marrow transplant
- Any other concomitant liver disease, including hemochromatosis, hepatitis C or D; Participants with severe steatohepatitis will be excluded (participants with non-alcoholic fatty liver disease \[NAFLD\] with steatosis only and/or mild to moderate steatohepatitis are acceptable)
- Positive anti-HIV
- Renal insufficiency with calculated (by Modification of Diet in Renal Disease (MDRD) method) creatinine clearance \<60 mL/min within 8 weeks prior to randomization
- Platelet count \<90,000 /mm3, hemoglobin \<13 g/dL (males) or \<12 g/dL (females), absolute neutrophil count \<1500 /mm\^3 (\<1000/mm\^3 for African-Americans) within 8 weeks prior to randomization
- History of active alcohol or drug abuse within 48 weeks of screening.
- Pre-existing psychiatric condition(s), including but not limited to: Current moderate or severe depression as determined by the study physician, history of depression requiring hospitalization within past 10 years, history of suicidal or homicidal attempt within the past 10 years, or history of severe psychiatric disorders including but not limited to schizophrenia, psychosis, bipolar disorder
- History of immune-mediated disease, or cerebrovascular, chronic pulmonary or cardiac disease associated with functional limitation, retinopathy, uncontrolled thyroid disease, poorly controlled diabetes or uncontrolled seizure disorder
- Any medical condition that would be predicted to be exacerbated by therapy or that would limit study participation
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (21)
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
University of California Los Angeles
Los Angeles, California, 90095, United States
California Pacific Medical Center
San Francisco, California, 94115, United States
University of California San Francisco
San Francisco, California, 94143, United States
Queen's Medical Center
Honolulu, Hawaii, 96813, United States
NIH Clinical Center
Bethesda, Maryland, 20892, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
University of Michigan Health System
Ann Arbor, Michigan, 48109, United States
University of Minnesota
Plymouth, Minnesota, 55446, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Saint Louis University
St Louis, Missouri, 63104, United States
Washington University
St Louis, Missouri, 63110, United States
University of North Carolina
Chapel Hill, North Carolina, 27599, United States
Duke University Medical Center
Durham, North Carolina, 27710, United States
Baylor University Medical Center
Dallas, Texas, 75246, United States
University of Texas Southwestern
Dallas, Texas, 75390, United States
Virginia Commonwealth University
Richmond, Virginia, 23498, United States
Virginia Mason Medical Center
Seattle, Washington, 98101, United States
University of Washington Medical Center
Seattle, Washington, 98105, United States
University of Toronto-Toronto Western Hospital
Toronto, Ontario, M5T 2S8, Canada
Related Publications (3)
Terrault NA, Sterling R, Lok AS, Ghany MG, Feld JJ, Cloherty G, Wahed AS, Yang X. Hepatitis B Virus RNA as a Biomarker for Safe Antiviral Discontinuation: A Prospective Study of Nucleos(t)ide Analogue Withdrawal. J Infect Dis. 2025 Jun 2;231(5):1290-1298. doi: 10.1093/infdis/jiae541.
PMID: 39478672DERIVEDFeld JJ, Wahed AS, Fried M, Ghany MG, Di Bisceglie AM, Perrillo RP, Khalili M, Yang X, Belle SH, Janssen HLA, Terrault N, Lok AS; Hepatitis B Research Network (HBRN). Withdrawal of Long-Term Nucleotide Analog Therapy in Chronic Hepatitis B: Outcomes From the Withdrawal Phase of the HBRN Immune Active Treatment Trial. Am J Gastroenterol. 2023 Jul 1;118(7):1226-1236. doi: 10.14309/ajg.0000000000002176. Epub 2023 Jan 13.
PMID: 36728214DERIVEDTerrault NA, Lok AS, Wahed AS, Ghany MG, Perrillo RP, Fried MW, Wong DK, Khalili M, Lau DTY, Sterling RK, Di Bisceglie AM, Lisker-Melman M, Cooper SL, Chung RT, Patel K, Roberts LR, Belle SH, Janssen HLA; Hepatitis B Research Network. Randomized Trial of Tenofovir With or Without Peginterferon Alfa Followed by Protocolized Treatment Withdrawal in Adults With Chronic Hepatitis B. Am J Gastroenterol. 2023 Jul 1;118(7):1214-1225. doi: 10.14309/ajg.0000000000002125. Epub 2022 Dec 23.
PMID: 36599136DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Abdus Wahed
- Organization
- University of Pittsburgh
Study Officials
- STUDY CHAIR
Averell Sherker, MD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- STUDY CHAIR
Edward Doo, MD
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- PRINCIPAL INVESTIGATOR
Anna Lok, MD
University of Michigan
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 6, 2011
First Posted
June 8, 2011
Study Start
November 1, 2012
Primary Completion
March 8, 2021
Study Completion
March 8, 2021
Last Updated
April 28, 2023
Results First Posted
October 12, 2022
Record last verified: 2023-04
Data Sharing
- IPD Sharing
- Will share
Data will be available at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repository https://repository.niddk.nih.gov/home/