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



Status:Recruiting
Conditions:Hepatitis
Therapuetic Areas:Immunology / Infectious Diseases
Healthy:No
Age Range:18 - Any
Updated:4/21/2016
Start Date:November 2012
End Date:October 2020
Contact:Michelle E Danielson, PhD
Email:danielsonm@edc.pitt.edu
Phone:412-624-5555

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Combination Therapy of Pegylated Interferon Alfa-2a and Tenofovir Versus Tenofovir Monotherapy in HBeAg-positive and HBeAg-negative Chronic Hepatitis B

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).

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.

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.
We found this trial at
21
sites
330 Brookline Ave
Boston, Massachusetts 02215
617-667-7000
Phone: 617-362-1098
Beth Israel Deaconess Medical Center Beth Israel Deaconess Medical Center (BIDMC) is one of the...
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185 Cambridge Street
Boston, Massachusetts 02114
617-724-5200
Phone: 617-724-7562
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Boston, MA
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3500 Gaston Avenue
Dallas, Texas 75246
1.800.422.9567
Phone: 214-820-2956
Baylor University Medical Center Baylor University Medical Center in Dallas, TX is ranked nationally in...
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8700 Beverly Blvd # 8211
Los Angeles, California 90048
(1-800-233-2771)
Phone: 310-423-1971
Cedars Sinai Med Ctr Cedars-Sinai is known for providing the highest quality patient care. Our...
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Los Angeles, California 90095
310-825-4321
Phone: 310-206-0645
University of California at Los Angeles The University of California, Los Angeles (UCLA) is an...
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1 Brookings Drive
St. Louis, Missouri 63110
 (314) 935-5000
Phone: 314-747-3969
Washington University Washington University creates an environment to encourage and support an ethos of wide-ranging...
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1500 E Medical Center Dr
Ann Arbor, Michigan 48109
(734) 936-4000
Phone: 734-936-7511
University of Michigan Health System The University of Michigan is home to one of the...
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Bethesda, Maryland 20892
Phone: 301-402-5115
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Chapel Hill, North Carolina 27599
(919) 962-2211
Phone: 919-966-2516
Univ of North Carolina Carolina’s vibrant people and programs attest to the University’s long-standing place...
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Dallas, Texas 75390
Phone: 214-645-6110
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2301 Erwin Rd
Durham, North Carolina 27710
919-684-8111
Phone: 919-668-2673
Duke Univ Med Ctr As a world-class academic and health care system, Duke Medicine strives...
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1301 Punchbowl St
Honolulu, Hawaii 96813
(808) 538-9011
Phone: 808-691-7609
Queen's Medical Center The Queen's Medical Center, located in downtown Honolulu, Hawaii, is a private,...
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Plymouth, Minnesota 55446
Phone: 612-625-8999
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Richmond, Virginia 23298
(804) 828-0100
Phone: 804-828-4060
Virginia Commonwealth University Since our founding as a medical school in 1838, Virginia Commonwealth University...
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Rochester, Minnesota 55905
Phone: 507-538-4877
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45 Castro Street
San Francisco, California 94114
(415) 600-6000
Phone: 415-600-1530
California Pacific Medical Center California Pacific Medical Center is one of the largest private, not-for-profit,...
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San Francisco, California 94143
Principal Investigator: Mandana Khalili, MD
Phone: 415-476-2227
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Seattle, Washington 98101
(888) 862-2737
Phone: 206-341-1452
Virginia Mason Medical Center Established in 1920, Virginia Mason began as an 80-bed hospital with...
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1959 NE Pacific St
Seattle, Washington 98195
(206) 598-3300
Phone: 206-598-4956
University of Washington Medical Center University of Washington Medical Center is one of the nation's...
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221 N Grand Blvd
St. Louis, Missouri 63103
(800) 758-3678
Phone: 314-577-8551
Saint Louis University Saint Louis University is a Catholic, Jesuit institution with campuses in St....
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Toronto, Ontario
Principal Investigator: Jordan Feld, MD, MPH
Phone: 416-603-5800
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