Trial record 8 of 435 for:    hepatitis b | Open Studies

Combination Therapy of Pegylated Interferon Alfa-2a and Tenofovir Versus Tenofovir Monotherapy in Chronic Hepatitis B (HBRN)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor:
Collaborator:
University of Pittsburgh
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT01369212
First received: June 6, 2011
Last updated: May 7, 2014
Last verified: May 2014
  Purpose

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).


Condition Intervention
Hepatitis B
Drug: Tenofovir
Drug: Peginterferon-alfa 2a and tenofovir

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Combination Therapy of Pegylated Interferon Alfa-2a and Tenofovir Versus Tenofovir Monotherapy in HBeAg-positive and HBeAg-negative Chronic Hepatitis B

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Hepatitis B surface antigen (HBsAg) loss [ Time Frame: week 240 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cumulative HBsAg loss [ Time Frame: Week 192 ] [ Designated as safety issue: No ]
  • Cumulative HBsAg loss [ Time Frame: Week 228 ] [ Designated as safety issue: No ]
  • Serious Adverse Events [ Time Frame: up to 240 weeks ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: up to 240 weeks ] [ Designated as safety issue: No ]
  • Hepatitis B e antigen (HBeAg) loss [ Time Frame: week 192 ] [ Designated as safety issue: No ]
  • Hepatitis B e antigen (HBeAg) loss [ Time Frame: week 228 ] [ Designated as safety issue: No ]
  • HBeAg loss [ Time Frame: week 240 ] [ Designated as safety issue: No ]
  • HBsAg seroconversion [ Time Frame: week 192 ] [ Designated as safety issue: No ]
  • HBsAg seroconversion [ Time Frame: week 228 ] [ Designated as safety issue: No ]
  • HBsAg seroconversion [ Time Frame: week 240 ] [ Designated as safety issue: No ]
  • HBeAg seroconversion [ Time Frame: week 192 ] [ Designated as safety issue: No ]
  • HBeAg seroconversion [ Time Frame: week 228 ] [ Designated as safety issue: No ]
  • HBeAg seroconversion [ Time Frame: week 240 ] [ Designated as safety issue: No ]
  • Normalization of Alanine Transaminase(ALT) levels [ Time Frame: week 192 ] [ Designated as safety issue: No ]
    males ≤30 U/L, females ≤20 U/L

  • Normalization of Alanine Transaminase(ALT) levels [ Time Frame: week 228 ] [ Designated as safety issue: No ]
    males ≤30 U/L, females ≤20 U/L

  • Normalization of Alanine Transaminase(ALT) levels [ Time Frame: week 240 ] [ Designated as safety issue: No ]
    males ≤30 U/L, females ≤20 U/L

  • HBV DNA <1000 IU/mL [ Time Frame: week 192 ] [ Designated as safety issue: No ]
  • HBV DNA <1000 IU/mL [ Time Frame: week 228 ] [ Designated as safety issue: No ]
  • HBV DNA <1000 IU/mL [ Time Frame: week 240 ] [ Designated as safety issue: No ]
  • HBV DNA <20 IU/mL(Lower limit of quantification [LLOQ]) of COBAS Ampliprep/COBAS TaqMan HBV v2.0 test) [ Time Frame: week 192 ] [ Designated as safety issue: No ]
  • HBV DNA <20 IU/mL(Lower limit of quantification [LLOQ]) of COBAS Ampliprep/COBAS TaqMan HBV v2.0 test) [ Time Frame: week 228 ] [ Designated as safety issue: No ]
  • HBV DNA <20 IU/mL(Lower limit of quantification [LLOQ]) of COBAS Ampliprep/COBAS TaqMan HBV v2.0 test) [ Time Frame: week 240 ] [ Designated as safety issue: No ]
  • Absence of detectable antiviral drug-resistance HBV mutations [ Time Frame: week 192 ] [ Designated as safety issue: No ]
  • Sustained HBV DNA <1000 IU/mL [ Time Frame: week 192 ] [ Designated as safety issue: No ]
  • Cumulative HBsAg loss [ Time Frame: Week 240 ] [ Designated as safety issue: No ]

Estimated Enrollment: 376
Study Start Date: November 2012
Estimated Study Completion Date: October 2020
Estimated Primary Completion Date: October 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tenofovir
Tenofovir 192 weeks
Drug: Tenofovir
300 mg daily for 192 weeks (4 years)
Other Names:
  • Hepatitis B
  • Viread
  • tenofovir
Experimental: Peginterferon-alfa 2a and tenofovir
A combination of peginterferon-alfa 2a plus tenofovir for 24 weeks and then tenofovir only for 168 weeks
Drug: Peginterferon-alfa 2a and tenofovir
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).
Other Names:
  • Hepatitis B
  • PEGASYS
  • Viread
  • tenofovir

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01369212

Contacts
Contact: Michelle E Danielson, PhD 412-624-5555 danielsonm@edc.pitt.edu
Contact: Joan MacGregor, MS 412-624-4300 macgreg@edc.pitt.edu

Locations
United States, California
University of California Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Steven Han, MD    310-206-0645    steven.han@ucla.edu   
Cedars Sinai Medical Center Not yet recruiting
Los Angeles, California, United States, 90048
Contact: Tram Tran, MD    310-423-1971    tram.tran@cshs.org   
University of California San Francisco Recruiting
San Francisco, California, United States, 94143
Contact: Norah Terrault    415-476-2227    norah.terrault@ucsf.edu   
Principal Investigator: Mandana Khalili, MD         
California Pacific Medical Center Recruiting
San Francisco, California, United States, 94115
Contact: Stewart Cooper, MD    415-600-1548    coopersl@sutterhealth.org   
United States, Hawaii
Queen's Medical Center Recruiting
Honolulu, Hawaii, United States, 96813
Contact: Naoky Tsai, MD    808-691-7609    naoky@hawaii.edu   
United States, Maryland
NIH Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: Marc Ghany, MD    301-402-5115    marcg@intra.niddk.nih.gov   
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Darryl Lau, MD    617-362-1098    dlau@bidmc.harvard.edu   
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Raymond T. Chung, MD    617-724-7562    rtchung@partners.org   
United States, Michigan
University of Michigan Health System Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Anna Lok, MD    734-936-7511    aslok@med.umich.edu   
United States, Minnesota
University of Minnesota Recruiting
Plymouth, Minnesota, United States, 55446
Contact: Coleman Smith, MD    612-871-1145 ext 2908    smith146@umn.edu   
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Lewis R. Roberts, MB, ChB, PhD    507-538-4877    roberts.lewis@mayo.edu   
United States, Missouri
Saint Louis University Recruiting
St. Louis, Missouri, United States, 63104
Contact: Adrian Di Bisceglie, MD    314-577-8551    dibiscam@slu.edu   
Washington University Recruiting
St. Louis, Missouri, United States, 63110
Contact: Mauricio Lisker-Melman, MD    314-747-3969    mlisker@dom.wustl.edu   
United States, North Carolina
University of North Carolina Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Michael W. Fried, MD    919-966-2516    mfried@med.unc.edu   
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Keyur Patel, MD    919-681-4044    keyur.patel@duke.edu   
United States, Texas
Baylor University Medical Center Recruiting
Dallas, Texas, United States, 75246
Contact: Robert Perrillo, MD    214-820-2956    roberper@baylorhealth.edu   
University of Texas Southwestern Recruiting
Dallas, Texas, United States, 75390
Contact: William Lee, MD    214-645-6110    william.lee@utsouthwestern.edu   
United States, Virginia
Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23498
Contact: Richard Sterling, MD    804-828-4060    rksterli@vcu.edu   
United States, Washington
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98105
Contact: Robert Carithers, MD    206-598-4956    robertc@medicine.washington.edu   
Virginia Mason Medical Center Recruiting
Seattle, Washington, United States, 98101
Contact: Kris Kowdley, MD    206-223-2319    kris.kowdley@vmmc.org   
Canada, Ontario
University of Toronto-Toronto Western Hospital Recruiting
Toronto, Ontario, Canada, M5T 2S8
Contact: Harry Janssen, MD    416-603-5800 ext 2776    harry.janssen@uhn.ca   
Principal Investigator: Jordan Feld, MD, MPH         
Principal Investigator: David K. Wong, MD, FRCP (C)         
Sub-Investigator: Joshua Juan, MD         
Sponsors and Collaborators
University of Pittsburgh
Investigators
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
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT01369212     History of Changes
Other Study ID Numbers: DK082864 HBRN Immune Active
Study First Received: June 6, 2011
Last Updated: May 7, 2014
Health Authority: United States: Institutional Review Board
United States: Federal Government

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Tenofovir disoproxil
Peginterferon alfa-2a
Interferon-alpha
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014