Entecavir Intensification for Persistent HBV Viremia in HIV-HBV Infection

May 17, 2013 updated by: University of California, San Francisco

Entecavir Intensification for Persistent Hepatitis B Virus (HBV) Viremia in HIV-HBV Infection

This study will evaluate HIV-HBV infected individuals who have evidence of HBV replication in the blood after taking 48 weeks of more of the HBV active medication tenofovir in combination with emtricitabine or lamivudine. Eligible participants will be randomized to receive 24 weeks of entecavir (ETV) 1 mg versus continued standard of care antiretroviral therapy. After 24 weeks, individuals on entecavir or who remain HBV viremic on standard of care will receive ETV o for an additional 24 weeks. The hypothesis is that intensification with entecavir will reduce HBV DNA at 24 weeks more than continued antiretroviral therapy without entecavir.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Design: This is a randomized, controlled pilot study of open-label entecavir for the treatment of persistent HBV viremia in HIV-HBV coinfected individuals who have failed to suppress HBV replication after 48 weeks on tenofovir containing therapy.

Primary Objective: To evaluate the mean log reduction of HBV DNA with entecavir(ETV) intensification in comparison to continued standard therapy with tenofovir and lamivudine/emtricitabine at 24 weeks of therapy

Study Population: HIV-HBV co-infected individuals with detectable HBV DNA after 48 weeks of therapy with tenofovir and lamivudine/emtricitabine whose HIV viremia is well controlled ( < 75 copies at time of enrollment)

Treatment: Subjects will be randomized to continue with standard therapy or to receive intensification with 1 mg daily of open label entecavir for the 24 week duration of the study.

Sample Size: 24 subjects will be enrolled.

Duration 24 weeks of treatment

Primary Endpoint: Mean log10 reduction of HBV DNA at 24 weeks of standard therapy vs. entecavir intensification.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94110
        • San Francisco General HIV Clinical Trials Group

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Ability and willingness to provide written informed consent
  • HIV infection, documented in patient medical record. Acceptable forms of documentation include positive HIV antibody or detectable HIV RNA.
  • Chronic HBV infection, defined as HBsAg positivity. Both hepatitis B "e" antigen (HBeAg) positive and negative subjects will be eligible.
  • Detectable HBV DNA ( > 160 copies/ml) after 48 weeks of therapy with TDF in conjunction with either 3TC or FTC
  • Compensated liver disease, defined as a Child-Pugh-Turcot(CPT) Score <7 at the time of enrollment.

Note: If Bilirubin in elevated, direct and indirect bilirubin levels will be evaluated. If only indirect bilirubin elevated, direct bilirubin will be used for CPT score. If BOTH direct and indirect bilirubin are elevated, total bilirubin will be used for the CPT score.

  • Stable antiretroviral therapy with no changes in the prior 8 weeks due to antiretroviral failure. HIV therapy modification for reasons other than virologic failure and without change in the tenofovir(TDF), lamivudine(3TC) or emtricitabine(FTC) moiety of the antiretroviral therapy will be permitted. HIV therapy must include TDF in conjunction with 3TC or FTC, and at least one other anti-HIV agent.
  • HIV RNA of <75 copies/ml within 8 weeks of study enrollment.
  • Estimated creatinine clearance by Cockcroft-Gault of ≥ 50 ml/min
  • Serum alpha-fetoprotein (AFP) of ≤50 ng/ml within 8 weeks of study entry, or if elevated > 50 ng/ml, an imaging study demonstrating no evidence of hepatic tumor within 8 weeks of enrollment.

  • Female study volunteers must not participate in a conception process (e.g., active attempt to become pregnant). If participating in sexual activity that could lead to pregnancy, the female study volunteer must use the following forms of contraception while receiving study-specific medication(s) and for 30 days after stopping the medication. One of the following methods MUST be used appropriately:

    • Condoms1 (male or female) with or without a spermicidal agent
    • Diaphragm or cervical cap with spermicide
    • intrauterine device(IUD)

    • Hormonal-based method

      1. Condoms are recommended because their appropriate use is the only contraception method effective for preventing HIV transmission.

Note: Subjects with concomitant Hepatitis C infection will be permitted to enroll.

Exclusion Criteria:

  • Allergy or sensitivity to study drug
  • Pregnancy, breastfeeding or unwillingness/inability to adhere to contraceptive methods for the duration of the study
  • Prisoners or subjects who are incarcerated.
  • Evidence of malignancy that would make the subject, in the opinion of the investigator, unsuitable for the study. This includes any systemic antineoplastic or immunomodulatory treatment or radiation within 24 weeks prior to study entry or the expectation that such treatment will be needed at any time during the study.
  • Receipt of systemic corticosteroids within 90 days prior to study entry (as this medication may increase HBV replication).
  • Investigational anti-HIV agents will be allowed on a case-by-case basis with the approval of the protocol team.
  • Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
  • Any active medical, psychiatric or social circumstance that in the opinion of the investigator puts the subject at potential risk from study participation or makes adherence to the study protocol unlikely.
  • Receipt of the following drugs with anti-HBV activity within 90 days prior to study entry or anticipated receipt during the course of the study including: adefovir(ADV), telbivudine, alpha interferon, penciclovir (Denavir) (except if given for < 4 weeks), famciclovir (Famvir), diaminopurine dioxolane (DAPD), clevudine (L-FMAU), thymosin alpha 1, ganciclovir (treatment limited to < 7 days is acceptable) (Cytovene), L-deoxythymidine, and L-deoxythymidine compounds and other investigational agents with anti-HBV activity.
  • Receipt of nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, vancomycin, cidofovir [Vistide], foscarnet [Foscavir], cisplatin, intravenous pentamidine [Pentam], oral tacrolimus [Prograf], cyclosporine [Sandimmune]) or the competitor of renal excretion, probenecid (Benemid), within 8 weeks prior to study entry or expected use of these agents during the course of the study. (Topical tacrolimus is allowed.)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
Entecavir 1 mg for 24 weeks in addition to continued standard of care antiretroviral therapy containing tenofovir in addition to emtricitabine or lamivudine
Drug: Entecavir with continued standard of care antiretroviral therapy
1 mg by mouth daily
Other Names:
  • Baraclude, Tenofovir, Truvada, Viread, 3TC, FTC, Epivir, Emtriva
Active Comparator: B
continued standard of care antiretroviral therapy which will include tenofovir in addition to emtricitabine or lamivudine
Drug: continued standard of care with tenofovir in addition to emtricitabine or lamivudine
continued standard of care with tenofovir in addition to emtricitabine or lamivudine
Other Names:
  • Tenofovir, Truvada, Viread, 3TC, FTC, Epivir, Emtriva

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hepatitis B Virus (HBV) DNA
Time Frame: week 24
HBV DNA carries the genetic blueprint of the virus. How many HBV DNA "particles" or "copies" are found in the blood indicates how rapidly the virus is reproducing in the liver.
week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Permanent Discontinuation Due to Toxicity
Time Frame: 24 weeks
24 weeks
Incidence of New Hepatic Decompensation( Ascites, Variceal Hemorrhage, Encephalopathy)
Time Frame: every 4 weeks for 24 weeks
every 4 weeks for 24 weeks
Incidence of ALT Flares
Time Frame: every 4 weeks for 24 weeks
ALT flare: sudden increase in blood level of alanine transaminase (ALT)
every 4 weeks for 24 weeks
HIV RNA < 75 Copies/ml
Time Frame: entry, week 12, and week 24
entry, week 12, and week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

Bristol-Myers Squibb

Investigators

  • Principal Investigator: Anne F Luetkemeyer, MD, HIV/AIDS Division, San Francisco General Hospital, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2008

Primary Completion (Actual)

February 1, 2010

Study Completion (Actual)

May 1, 2010

Study Registration Dates

First Submitted

April 16, 2008

First Submitted That Met QC Criteria

April 17, 2008

First Posted (Estimate)

April 21, 2008

Study Record Updates

Last Update Posted (Estimate)

May 27, 2013

Last Update Submitted That Met QC Criteria

May 17, 2013

Last Verified

May 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A109324
  • AI463-162

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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