Overview

This trial is active, not recruiting.

Condition hepatitis b
Treatment entecavir and peginterferon
Phase phase 3
Sponsor National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator University of Pittsburgh
Start date May 2012
End date February 2017
Trial size 28 participants
Trial identifier NCT01369199, DK082864 HBRN IT Adult Trial, NCT01534611

Summary

The investigators propose to evaluate 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. The investigators hypothesize that using a potent nucleos(t)ide analogue will provide a higher rate of loss of HBeAg loss and suppression of HBV DNA.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
A combination of 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon.
entecavir and peginterferon PEGASYS, peginterferon alfa 2a, Baraclude
Entecavir 0.5 mg daily orally for 48 weeks plus peginterferon 180 µg sq weekly during weeks 9-48 of treatment.

Primary Outcomes

Measure
Safety: Number, type and rate of adverse events/serious adverse events through treatment and end of follow-up 48 weeks after stopping treatment. Efficacy: HBeAg loss (lack of detectable HBeAg) AND HBV DNA ≤1,000 IU/mL 48 weeks after stopping treatment.
time frame: at 96 weeks

Secondary Outcomes

Measure
HBeAg loss
time frame: at week 48
HBeAg loss
time frame: at week 96
HBeAg seroconversion
time frame: at week 48
HBeAg seroconversion
time frame: at week 96
Time to HBsAg loss
time frame: at week 48
Time to HBsAg loss
time frame: at week 96
ALT <45 IU/L for men, <30 IU/L for women (approximately 1.5 ULN)
time frame: at week 48
ALT <45 IU/L for men, <30 IU/L for women (approximately 1.5 ULN)
time frame: at week 96
ALT normalization (men <30 IU/L, women <20 IU/L)
time frame: at week 48
ALT normalization (men <30 IU/L, women <20 IU/L)
time frame: at week 96
HBV DNA ≤1000 IU/mL
time frame: at week 48
HBV DNA ≤1000 IU/mL
time frame: at week 96
HBV DNA <20 IU/mL (LLOQ of COBAS Ampliprep/COBAS TaqMan HBV v2.0 test)
time frame: at week 48
HBV DNA <20 IU/mL (LLOQ of COBAS Ampliprep/COBAS TaqMan HBV v2.0 test)
time frame: at week 96

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - 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 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-HBc 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 IU/L in males, ≤30 IU/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 HCC based upon alpha-fetoprotein (AFP) ≤20 ng/mL at screening visit (up to 6 weeks prior to baseline visit). a. Participants who meet 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: - History of hepatic decompensation - Evidence of decompensated liver disease prior to or during screening, including direct bilirubin >0.5 mg/dL, 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 NALFD with severe steatohepatitis is exclusionary. - Presence of anti-HDV or anti-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.

Additional Information

Official title Combination Entecavir and Peginterferon Therapy in HBeAg-Positive Immune-Tolerant Adults With Chronic Hepatitis B
Description To determine the efficacy of treatment with 8 weeks of entecavir followed by 40 weeks of both entecavir and peginterferon in the treatment of chronic hepatitis B in hepatitis B "e" antigen (HBeAg) positive adults who are in the immune tolerant phase. To evaluate "off treatment" 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 ALT levels and high serum levels of HBV DNA ("immune tolerant" HBeAg-positive chronic hepatitis B). All participants will be followed until week 96 (48 weeks after discontinuation of therapy in the treatment group) at which time the primary outcome will be measured.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).