Combination Therapy of Pegylated Interferon Alfa-2a and Tenofovir Versus Tenofovir Monotherapy in Chronic Hepatitis B (HBRN)
This study is currently recruiting participants.
Verified April 2013 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: April 30, 2013
Last verified: April 2013
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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 sustained HBsAg loss in serum one year after stopping all antiviral therapy (sustained off-treatment response).
| Condition | Intervention |
|---|---|
|
Hepatitis B |
Drug: Tenofovir Drug: Combination of 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:
Drug Information available for:
Interferon
Interferon Alfa-2a
Tenofovir
Peginterferon Alfa-2a
Tenofovir Disoproxil Fumarate
Recombinant Hepatitis B vaccine
Hepatitis A Vaccines
U.S. FDA Resources
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 IU/L, females ≤20 IU/L
- Normalization of Alanine Transaminase(ALT) levels [ Time Frame: week 228 ] [ Designated as safety issue: No ]males ≤30 IU/L, females ≤20 IU/L
- Normalization of Alanine Transaminase(ALT) levels [ Time Frame: week 240 ] [ Designated as safety issue: No ]males ≤30 IU/L, females ≤20 IU/L
- Proportion with HBV DNA ≤1000 IU/mL [ Time Frame: week 192 ] [ Designated as safety issue: Yes ]
- Proportion with HBV DNA ≤1000 IU/mL [ Time Frame: week 228 ] [ Designated as safety issue: Yes ]
- Proportion with HBV DNA ≤1000 IU/mL [ Time Frame: week 240 ] [ Designated as safety issue: Yes ]
- Proportion with HBV DNA <20 IU/mL [ Time Frame: week 192 ] [ Designated as safety issue: Yes ]
- Proportion with HBV DNA <20 IU/mL [ Time Frame: week 228 ] [ Designated as safety issue: Yes ]
- Proportion with HBV DNA <20 IU/mL [ Time Frame: week 240 ] [ Designated as safety issue: Yes ]
- Absence of detectable antiviral drug-resistance HBV mutations [ Time Frame: week 192 ] [ Designated as safety issue: No ]
- Stable or improved Ishak fibrosis score compared to pre-treatment [ Time Frame: Week 192 ] [ Designated as safety issue: No ]
- Improved necroinflammation defined by HAI reduction of ≥2 points (compared to pre-treatment). [ Time Frame: week 192 ] [ Designated as safety issue: No ]
- Sustained HBV DNA <1000 IU/ml AND "mild" histology defined as HAI ≤3 AND improvement in Ishak fibrosis score by ≥ 1 [ Time Frame: week 192 ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 376 |
| Study Start Date: | October 2012 |
| Estimated Study Completion Date: | October 2018 |
| Estimated Primary Completion Date: | October 2017 (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 Name: Hepatitis B, tenofovir, Viread
|
|
Experimental: Peginterferon and tenofovir
A combination of peginterferon alfa 2a plus tenofovir for 24 weeks and then tenofovir only for 168 weeks
|
Drug: Combination of 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.
Other Name: PEGASYS, peginterferon alfa 2a, Viread, and 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). A liver biopsy will be obtained at the end-of-treatment (week 192) to assess improvement in histology. 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) and has completed the baseline evaluation
- 18 years or older
Chronic hepatitis B infection as evidenced by either of the following:
- HBsAg positive result at screening (within 8 weeks prior to randomization) and another time at least 24 weeks prior to randomization with no HBsAg negative result in between.
- HBsAg positive plus absence of detectable anti-HBc IgM in serum at screening (within 8 weeks prior to randomization).
- Hepatitis B e antigen positive or negative
- Serum HBV DNA ≥1000 IU/mL on 2 occasions at least 4 weeks, and no more than 24 weeks, apart with the second being within 8 weeks of randomization
- Two elevated serum ALT levels 4 weeks apart, and no more than 24 weeks apart, with the second being within 8 weeks of randomization
- Treatment Naive for the last 48 weeks
- Compensated liver disease
- No evidence of HCC
- Liver biopsy (done as standard of care) that shows findings consistent with chronic hepatitis B with histology activity index (HAI) ≥5 (necroinflammatory component only) or Ishak fibrosis score ≥2 or both, as assessed by the local study pathologist on review of a liver biopsy done within 96 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 IU/L for males and ≥300 IU/L for females
- History of hepatic decompensation including but not limited to ascites, variceal bleeding, or hepatic encephalopathy
- Liver biopsy with ≥3+/4 iron in hepatocytes by Prussian blue stain
- 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 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 <50 mL/min, at the screening visit
- Platelet count <90,000 /mm3, hemoglobin <13 g/dl (males) or <12 g/dl (females), absolute neutrophil count <1500 /mm3 (<1000/mm3 for African-Americans) during the screening visit
- 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 and 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
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: Ethan Obstarczyk, BA | 412-383-9584 | obstarczyke@edc.pitt.edu |
Locations
| United States, California | |
| University of California Los Angeles | Not yet 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 | |
| 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 - Liver Center | Recruiting |
| Honolulu, Hawaii, United States, 96813 | |
| Contact: Naoky Tsai, MD 808-691-7609 naoky@hawaii.edu | |
| United States, Maryland | |
| NIH Clinical Center | Not yet 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: Ray 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 | Not yet 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: W. Ray Kim, MD 507-538-0254 kim.woong@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: Micheal 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 | Not yet 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 Caithers, MD 206-598-4956 doctorc@u.washington.edu | |
| Virginia Mason Medical Center | Recruiting |
| Seattle, Washington, United States, 98101 | |
| Contact: Kris Kowdley, MD 206-223-2319 kkowdley@benaroyaresearch.org | |
| Canada, Ontario | |
| University of Toronto-Toronto Western Hospital | Recruiting |
| Toronto, Ontario, Canada, M5T 2S8 | |
| Contact: David Wong, MD 416-603-5800 ext 5118 dave.wong.uhn@gmail.com | |
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: | April 30, 2013 |
| Health Authority: | United States: Institutional Review Board United States: Federal Government |
Additional relevant MeSH terms:
|
Hepatitis Hepatitis A Hepatitis B Hepatitis, Chronic Hepatitis B, Chronic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections Hepadnaviridae Infections DNA Virus Infections Interferon-alpha |
Interferon Alfa-2a Interferons Tenofovir Tenofovir disoproxil Peginterferon alfa-2a Antiviral Agents Anti-Infective Agents Therapeutic Uses Pharmacologic Actions Immunologic Factors Physiological Effects of Drugs Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Growth Inhibitors |
ClinicalTrials.gov processed this record on May 16, 2013