Combination Entecavir and Peginterferon Therapy in HBeAg-Positive Immune-Tolerant Adults With Chronic Hepatitis B

NCT01369199 | Terminated Phase 3 Results DMC FDA Drug

• 22 other identifiers: DK082864 HBRN IT Adult TrialU01DK082916U01DK082843U01DK082863U01DK082864U01DK082866U01DK082867U01DK082871U01DK082872U01DK082874U01DK082919U01DK082923U01DK082927U01DK082943U01DK082944P30DK050306A-DK-3002-001M01RR000040UL1TR000058UL1TR000004UL1TR001111UL1RR024986
• Study Type: interventional
• Target: 28
• Locations: 2 countries
• Sites: 21

Brief Summary

The investigators evaluated the safety and efficacy of a short lead-in course (8 weeks) of entecavir followed by combination of entecavir plus peginterferon alfa-2a for 40 weeks.

Conditions

Hepatitis B

Keywords

Hepatitis B; Immune-tolerant hepatitis B; HBV

Outcome Measures

Primary Outcomes (3)

• Proportion of Participants With HBeAg Loss (Lack of Detectable HBeAg) AND HBV DNA ≤1,000 IU/mL

  Lack of data was considered to be treatment failure.

  End of follow-up (up to 96 weeks)

• Incidence of Adverse Events (AEs) Per Person-Year of Observation

  The number of AEs includes both AEs and Serious Adverse Events (SAEs). The incidence is calculated as the number of AEs divided by the number of person-years of observation, which is the sum, across all participants, of the number of years between the start of treatment and the end of treatment, or the end of follow-up, respectively.

  From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)

• Incidence of Serious Adverse Events (SAEs) Per Person-Year

  The incidence is calculated as the number of SAEs divided by the number of person-years of observation, which is the sum, across all participants, of the number of years between the start of treatment and the end of treatment, or the end of follow-up, respectively.

  From first treatment to the end of treatment (up to 48 weeks) and the end of follow-up (up to 96 weeks)

Secondary Outcomes (17)

• Proportion of Participants With HBeAg Loss

  End of treatment (up to 48 weeks)

• Proportion of Participants With HBeAg Loss

  End of follow-up (up to 96 weeks)

• Proportion of Participants With HBeAg Seroconversion

  End of treatment (up to 48 weeks)

• Proportion of Participants With HBeAg Seroconversion

  End of follow-up (up to 96 weeks)

• Proportion of Participants With HBsAg Loss

  End of treatment (up to 48 weeks)

Study Arms (1)

Peginterferon and entecavir

EXPERIMENTAL

A combination of 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon.

Drug: Entecavir and peginterferon

Interventions

Entecavir and peginterferon DRUG

Entecavir 0.5 mg daily orally for 48 weeks plus peginterferon 180 µg sq weekly during weeks 9-48 of treatment.

Also known as: PEGASYS, peginterferon alfa 2a, Baraclude

Peginterferon and entecavir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Enrolled in \& completed the baseline evaluation for NCT01263587 or completed the necessary components of NCT01263587 by the end of baseline visit.
• \>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.

You may not qualify if:

• History of hepatic decompensation
• 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).
• 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).

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead
• University of Pittsburgh: collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (21)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

Queen's Medical Center

Honolulu, Hawaii, 96813, United States

Location

NIH Clinical Center

Bethesda, Maryland, 20892, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55446, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23498, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

University of Washington Medical Center

Seattle, Washington, 98105, United States

Location

University of Toronto

Toronto, Ontario, M5T 2S8, Canada

Location

Related Links

• Click here for more information about the Hepatitis B Research Network

MeSH Terms

Conditions

Hepatitis B

Interventions

entecavir; peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Limitations and Caveats

Early termination of recruitment per Data and Safety Monitoring Board. 1 case with multiple central and local lab discrepancies was not considered to have HBeAg loss since central lab was always negative.

Results Point of Contact

• Title: Dr. Steven Belle
• Organization: University of Pittsburgh

belle@edc.pitt.edu

412-624-5419

Study Officials

• Averell Sherker, MD

  National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  STUDY CHAIR

• Anna Lok, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2011
• First Posted: June 8, 2011
• Study Start: May 1, 2012
• Primary Completion: February 14, 2017
• Study Completion: February 14, 2017
• Last Updated: May 26, 2022
• Results First Posted: July 3, 2018

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: At completion of HBRN project. Length of availability determined by NIDDK data repository.
• Access Criteria: Per NIDDK-supported data repository

Locations

CA (1); US (20)