Combination Therapy of Pegylated Interferon Alfa-2a and Tenofovir Versus Tenofovir Monotherapy in Chronic Hepatitis B
Information source: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hepatitis B
Intervention: Tenofovir (Drug); Peginterferon-alfa 2a and tenofovir (Drug)
Phase: N/A
Status: Recruiting
Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Official(s) and/or principal investigator(s): Averell Sherker, MD, Study Chair, Affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Edward Doo, MD, Study Chair, Affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Anna Lok, MD, Principal Investigator, Affiliation: University of Michigan
Overall contact: Michelle E Danielson, PhD, Phone: 412-624-5555, Email: danielsonm@edc.pitt.edu
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).
Clinical Details
Official title: Combination Therapy of Pegylated Interferon Alfa-2a and Tenofovir Versus Tenofovir Monotherapy in HBeAg-positive and HBeAg-negative Chronic Hepatitis B
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Hepatitis B surface antigen (HBsAg) loss
Secondary outcome: Cumulative HBsAg lossCumulative HBsAg loss Serious Adverse Events Adverse events Hepatitis B e antigen (HBeAg) loss Hepatitis B e antigen (HBeAg) loss HBeAg loss HBsAg seroconversion HBsAg seroconversion HBsAg seroconversion HBeAg seroconversion HBeAg seroconversion HBeAg seroconversion Normalization of Alanine Transaminase(ALT) levels Normalization of Alanine Transaminase(ALT) levels Normalization of Alanine Transaminase(ALT) levels HBV DNA <1000 IU/mL HBV DNA <1000 IU/mL HBV DNA <1000 IU/mL HBV DNA <20 IU/mL(Lower limit of quantification [LLOQ]) of COBAS Ampliprep/COBAS TaqMan HBV v2.0 test) HBV DNA <20 IU/mL(Lower limit of quantification [LLOQ]) of COBAS Ampliprep/COBAS TaqMan HBV v2.0 test) HBV DNA <20 IU/mL(Lower limit of quantification [LLOQ]) of COBAS Ampliprep/COBAS TaqMan HBV v2.0 test) Absence of detectable antiviral drug-resistance HBV mutations Sustained HBV DNA <1000 IU/mL Cumulative HBsAg loss
Detailed description:
The objective of this study is to compare the long-term efficacy of treatment with
combination therapy with peginterferon plus tenofovir versus tenofovir monotherapy in the
treatment of chronic hepatitis B.
This is a randomized (1: 1) parallel group design trial comparing (i) Tenofovir DF 300 mg
daily for 192 weeks (4 years) and (ii) peginterferon alfa-2a 180 µg weekly for 24 weeks plus
Tenofovir DF 300 mg daily for 192 weeks (4 years). Enrolled participants will be stratified
by HBeAg status (positive/negative), genotype (A vs. all others) and cirrhosis (present vs.
absent). After 192 weeks of treatment, participants meeting criteria for treatment
discontinuation will stop treatment and be followed for 48 weeks (total duration of
treatment and follow up is 240 weeks). Emtricitabine/tenofovir coformulated as Truvada,
approved for treatment of HIV but not for treatment of HBV infection, will be offered to
patients with primary nonresponse, partial virological response or confirmed virologic
breakthrough.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion criteria:
- 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
- 18 years or older
- Chronic hepatitis B infection as evidenced by at least one of the following:
1. 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.
2. 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 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 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
Exclusion criteria:
- 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 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
- 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
last 144 weeks (except adequately treated carcinoma in situ or basal cell carcinoma
of the skin)
- Need for ongoing use of any antivirals with activity against HBV during the course of
the study
- Any other condition that in the opinion of the investigator would make the
participant unsuitable for enrollment or could interfere with the participant
participating in and completing the study.
- Participation in any other clinical trial involving investigational drugs within 30
days of randomization or intention to participate in another clinical trial during
this study.
Locations and Contacts
Michelle E Danielson, PhD, Phone: 412-624-5555, Email: danielsonm@edc.pitt.edu
Cedars Sinai Medical Center, Los Angeles, California 90048, United States; Recruiting Tram T. Tran, MD, Phone: 310-423-1971, Email: tram.tran@cshs.org
University of California Los Angeles, Los Angeles, California 90095, United States; Recruiting Steven Han, MD, Phone: 310-206-0645, Email: steven.han@ucla.edu
California Pacific Medical Center, San Francisco, California 94115, United States; Recruiting Stewart Cooper, MD, Phone: 415-600-1530, Email: coopersl@sutterhealth.org Phone: 415-600-1020
University of California San Francisco, San Francisco, California 94143, United States; Recruiting Norah Terrault, Phone: 415-476-2227, Email: norah.terrault@ucsf.edu Mandana Khalili, MD, Principal Investigator
Queen's Medical Center, Honolulu, Hawaii 96813, United States; Recruiting Naoky Tsai, MD, Phone: 808-691-7609, Email: naoky@hawaii.edu
NIH Clinical Center, Bethesda, Maryland 20892, United States; Recruiting Marc Ghany, MD, Phone: 301-402-5115, Email: marcg@intra.niddk.nih.gov
Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, United States; Recruiting Darryl Lau, MD, Phone: 617-362-1098, Email: dlau@bidmc.harvard.edu
Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Recruiting Raymond T. Chung, MD, Phone: 617-724-7562, Email: rtchung@partners.org
University of Michigan Health System, Ann Arbor, Michigan 48109, United States; Recruiting Anna Lok, MD, Phone: 734-936-7511, Email: aslok@med.umich.edu
University of Minnesota, Plymouth, Minnesota 55446, United States; Recruiting Mohamed Hassan, MD, Phone: 612-625-8999, Email: hassan042@umn.edu Phone: 612-626-1716
Mayo Clinic, Rochester, Minnesota 55905, United States; Recruiting Lewis R. Roberts, MB, ChB, PhD, Phone: 507-538-4877, Email: roberts.lewis@mayo.edu
Saint Louis University, St. Louis, Missouri 63104, United States; Recruiting Adrian Di Bisceglie, MD, Phone: 314-577-8551, Email: dibiscam@slu.edu
Washington University, St. Louis, Missouri 63110, United States; Recruiting Mauricio Lisker-Melman, MD, Phone: 314-747-3969, Email: mlisker@dom.wustl.edu
University of North Carolina, Chapel Hill, North Carolina 27599, United States; Recruiting Michael W. Fried, MD, Phone: 919-966-2516, Email: mfried@med.unc.edu
Duke University Medical Center, Durham, North Carolina 27710, United States; Recruiting Keyur Patel, MD, Phone: 919-681-4044, Email: keyur.patel@duke.edu
University of Toronto-Toronto Western Hospital, Toronto, Ontario M5T 2S8, Canada; Recruiting Harry Janssen, MD, Phone: 416-603-5800, Ext: 2776, Email: harry.janssen@uhn.ca Jordan Feld, MD, MPH, Principal Investigator David K. Wong, MD, FRCP (C), Principal Investigator Joshua Juan, MD, Sub-Investigator
Baylor University Medical Center, Dallas, Texas 75246, United States; Recruiting Robert Perrillo, MD, Phone: 214-820-2956, Email: roberper@baylorhealth.edu
University of Texas Southwestern, Dallas, Texas 75390, United States; Recruiting William Lee, MD, Phone: 214-645-6110, Email: william.lee@utsouthwestern.edu
Virginia Commonwealth University, Richmond, Virginia 23498, United States; Recruiting Richard Sterling, MD, Phone: 804-828-4060, Email: rksterli@vcu.edu
University of Washington Medical Center, Seattle, Washington 98105, United States; Recruiting Robert Carithers, MD, Phone: 206-598-4956, Email: robertc@medicine.washington.edu
Virginia Mason Medical Center, Seattle, Washington 98101, United States; Recruiting Chia Wang, MD, MS, Phone: 206-341-1452, Email: chia.wang@vmmc.org Phone: 206-341-1021
Additional Information
Hepatitis B Research Network
Starting date: November 2012
Last updated: February 2, 2015
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