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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 loss

Cumulative 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

Page last updated: August 23, 2015

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