Combination Entecavir and Peginterferon Therapy in HBeAg-Positive Immune-Tolerant Adults With Chronic Hepatitis B
NCT ID: NCT01369199
Last Updated: 2022-05-26
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
TERMINATED
PHASE3
28 participants
INTERVENTIONAL
2012-05-31
2017-02-14
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Efficacies of Entecavir Add on HBeAg Negative Patients With HBV DNA Positive During Peginterferon Alpha 2a Treatment
NCT02365402
Sequential/Combination Therapy in Nucleoside or Nucleotide Analogue (NA)-Suppressed Chronic Hepatitis B Patients
NCT03332329
Entecavir/Pegylated Interferon in Immune Tolerant Children With Chronic Hepatitis B Virus (HBV) Infection
NCT01368497
Efficacy Optimizing Extension Study of Chronic Hepatitis B Patients With Inadequate Response to NUC Therapy
NCT01829685
Switch or Sequential Combination Therapy of Peginterferon in Hepatitis B Patients With Longterm Entecavir Therapy
NCT02589652
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
To evaluate safety and sustained responses after treatment with entecavir and peginterferon alfa-2a in the treatment of chronic hepatitis B in HBeAg positive adults who are in the immune tolerant phase.
A single arm treatment study of 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon alfa-2a in adults with HBeAg-positive chronic hepatitis B with normal or near normal alanine aminotransferase (ALT) levels and high serum levels of hepatitis B virus (HBV) DNA ("immune tolerant" HBeAg-positive chronic hepatitis B). All participants followed for 48 weeks after treatment discontinuation (week 96 for those who completed treatment).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Peginterferon and entecavir
A combination of 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon.
Entecavir and peginterferon
Entecavir 0.5 mg daily orally for 48 weeks plus peginterferon 180 µg sq weekly during weeks 9-48 of treatment.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Entecavir and peginterferon
Entecavir 0.5 mg daily orally for 48 weeks plus peginterferon 180 µg sq weekly during weeks 9-48 of treatment.
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* \>18 years of age at the baseline visit (day 0). Patients \>50 years of age at baseline will need to have a liver biopsy as standard of care with hepatic activity index (HAI) ≤3 \& Ishak fibrosis score ≤1 within 96 weeks prior to baseline visit.
* Documented chronic HBV infection as evidenced by detection of HBsAg in serum for ≥24 weeks prior to baseline visit OR at least one positive HBsAg \& negative anti-hepatitis B core (HBc) immunoglobulin (IgM) within 24 weeks prior to baseline visit OR at least one positive HBsAg \& two positive HBV DNA over a period of ≥24 weeks prior to baseline visit.
* Presence of HBeAg in serum at last screening visit within 6 weeks of baseline visit.
* Serum HBV DNA level \>10˄7 IU/mL on at least two occasions at least 12 weeks apart during the 52 weeks before baseline visit. One of the two HBV DNA levels must be within 6 weeks of baseline visit.
* ALT levels persistently ≤45 U/L in males, ≤30 U/L in females (approx. 1.5 times the upper limit of normal (ULN) range) as documented by at least three values: one taken 28-52 weeks before baseline visit, one taken 6 to 24 weeks before the baseline visit, \& the final value within 6 weeks prior to baseline visit.
* No evidence of hepatocellular carcinoma (HCC) based upon alpha-fetoprotein (AFP) ≤20 ng/mL at screening visit (up to 6 weeks prior to baseline visit). a. Participants who meet American Association for the Study of Liver Diseases (AASLD) criteria for HCC surveillance must have negative liver imaging as shown by ultrasound, computerized tomography (CT) or magnetic resonance imaging (MRI) within 28 weeks prior to baseline visit. b. Participants with AFP \>20 ng/mL must be evaluated clinically with additional imaging \& shown not to have HCC on CT or MRI before they can be enrolled.
Exclusion Criteria
* Evidence of decompensated liver disease prior to or during screening, including direct bilirubin \>0.5 mg/dL, international normalization ratio (INR) \>1.5, or serum albumin \<3.5 g/dL.
* Platelet count \<120,000/mm3, hemoglobin \<13 g/dL (males) or \<12 g/dL (females), absolute neutrophil count \< 1500 /mm3 (\<1000/mm3 for African-Americans) at last screening visit.
* Previous treatment with medications that have established activity against HBV including interferon \& nucleos(t)ide analogs ≥24 weeks. Patients with \<24 weeks of prior HBV treatment \& a wash-out period \>24 weeks are not excluded.
* Known allergy or intolerance to study medications.
* Females who are pregnant or breastfeeding. Females of childbearing potential unable or unwilling to use a reliable method of contraception during the treatment period.
* Renal insufficiency with calculated creatinine clearance \<50 mL/min at screening.
* History of alcohol or drug abuse within 48 weeks of baseline visit.
* Previous liver or other organ transplantation (including engrafted bone marrow).
* Any other concomitant liver disease, including hepatitis C or D. Non-alcoholic fatty liver disease (NAFLD) with steatosis \&/or mild to moderate steatohepatitis is acceptable but NAFLD with severe steatohepatitis is exclusionary.
* Presence of anti-hepatitis D virus (HDV) or anti-hepatitis C virus (HCV) (unless HCV RNA negative) in serum on any occasion in the 144 weeks prior to baseline visit. Presence of anti-HIV (test completed within 6 weeks prior to baseline visit).
* Pre-existing psychiatric condition(s), including, but not limited to: current moderate or severe depression, history of depression requiring hospitalization within the past 10 years, history of suicidal or homicidal attempt within the past 10 years, history of severe psychiatric disorders as determined by a study physician.
* History of immune-mediated or cerebrovascular disease, chronic pulmonary or cardiac disease associated with functional limitation, retinopathy, uncontrolled thyroid disease, poorly controlled diabetes or uncontrolled seizure disorder, as determined by a study physician.
* Any medical condition that would, in the opinion of a study physician, be predicted to be exacerbated by therapy or that would limit study participation.
* Any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids or other immunosuppressive medications during the course of this study.
* Evidence of active or suspected malignancy, or a history of malignancy within the 144 weeks prior to baseline visit (except adequately treated carcinoma in situ or basal cell carcinoma of the skin).
* Expected need for ongoing use of any antivirals with activity against HBV during the course of the study.
* Concomitant use of complementary or alternative medications purported to have antiviral activity.
* Participation in any other clinical trial involving investigational drugs within 30 days of the baseline visit or intention to participate in another clinical trial involving investigational drugs during participation in this study.
18 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
University of Pittsburgh
OTHER
National Center for Research Resources (NCRR)
NIH
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
NIH
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Averell Sherker, MD
Role: STUDY_CHAIR
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Anna Lok, MD
Role: PRINCIPAL_INVESTIGATOR
University of Michigan
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Cedars Sinai Medical Center
Los Angeles, California, United States
University of California Los Angeles
Los Angeles, California, United States
California Pacific Medical Center
San Francisco, California, United States
University of California San Francisco
San Francisco, California, United States
Queen's Medical Center
Honolulu, Hawaii, United States
NIH Clinical Center
Bethesda, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
University of Michigan Health System
Ann Arbor, Michigan, United States
University of Minnesota
Minneapolis, Minnesota, United States
Mayo Clinic
Rochester, Minnesota, United States
Saint Louis University
St Louis, Missouri, United States
Washington University
St Louis, Missouri, United States
University of North Carolina
Chapel Hill, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
Baylor University Medical Center
Dallas, Texas, United States
University of Texas Southwestern
Dallas, Texas, United States
Virginia Commonwealth University
Richmond, Virginia, United States
Virginia Mason Medical Center
Seattle, Washington, United States
University of Washington Medical Center
Seattle, Washington, United States
University of Toronto
Toronto, Ontario, Canada
Countries
Review the countries where the study has at least one active or historical site.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
A-DK-3002-001
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
DK082864 HBRN IT Adult Trial
Identifier Type: -
Identifier Source: org_study_id
NCT01534611
Identifier Type: -
Identifier Source: nct_alias
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.