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Hepatitis BPhase 2NCT00013702

Adefovir Dipivoxil to Treat Hepatitis B in HIV-Infected Patients

A Phase 2 study testing Adefovir in people with Hepatitis B and HIV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will evaluate the safety and effectiveness of adding the experimental drug adefovir dipivoxil to lamivudine for treating hepatitis B virus (HBV) infection in HIV-infected patients with liver cirrhosis. Adefovir inhibits HBV by interfering with replication of the virus's genetic material. Read more about this study

Who is it for?
Any age
Conditions the study is for
Hepatitis B, HIV Infection
What is being tested?
Adefovir
How many people
30 participants
Where
1 siteUnited States
Study dates
Mar 2001to Feb 2004
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age greater than or equal to 18 years
  • Infection with HBV with HBV viral load greater than or equal to 1.0 x 10(6) copies/mL by Roche assay at screen
  • HIV-infected as documented by ELISA and Western Blot in NIAID clinic (any CD4/HIV viral load)
  • Decompensated cirrhosis (Child-Pugh Score greater than or equal to 7: Class B or C cirrhosis)
  • Class A with Score of 6 acceptable if secondary to ascites grading and not encephalopathy or laboratory abnormality (PT, albumin, bilirubin).
  • Able to return to NIH for study visits
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  • Have a physician(s) outside of NIH who will provide routine, as well as HIV and liver specific, care.
  • Receiving lamivudine at a dose of at least 100 mg qd for greater than or equal to one year prior to enrollment (with no dosing interruptions of greater than 1 month total in the previous year and no interruption in the 3 months prior to study entry)
  • Serum creatinine less than 1.5 mg/dL
  • Serum phosphorus greater than or equal to 2.2 mg/dL (normal range NIH 2.3-4.3 mg/dL)
  • Neutrophil count greater than or equal to 1000 cells/mm(3)
  • Platelets greater than or equal to 50,000/mm(3)
  • Hemoglobin greater than or equal to 8.0 mg/dL
  • ALT less than or equal to 287 (7 X the NIH upper limit of normal)
  • Not pregnant or breast-feeding. Pregnancy test must be negative within two weeks prior to dosing with study medications.
  • If capable of pregnancy: use of effective contraception during study: effective contraception methods include abstinence, surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap or sponge, or use of hormonal contraception with an anti-HIV regimen that will not alter metabolism of hormonal contraception
  • Willing and able to provide written informed consent
  • Because liver disease can result in encephalopathy, willing to designate a person for durable power of attorney on the NIH form for medical research and medical care purposes at the NIH Clinical Center

Who cannot join

  • Prior use of ADV (outside of patient receiving adefovir from NIH under emergency use IND) or prior use of tenofovir, or cidofovir
  • Active serious systemic infections other than HIV or HBV
  • Liver disease caused by reasons other than hepatitis B e.g., HCV, HDV, Wilson's, hemochromatosis, autoimmune hepatitis (ANA greater than or equal to 160) except history of drug-associated hepatitis with discontinuation of causative agent
  • History of significant encephalopathy
  • History of clinically significant pancreatitis
  • History of untreated varices
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  • New AIDS-defining event other than esophageal candidiasis diagnosed within one month prior to baseline
  • Decompensated heart failure
  • Treatment with immunomodulator drugs (interferons, interleukins, corticosteroids in greater than physiologic doses) in the 4 weeks prior to baseline. G-CSF and epoietin use are permitted.
  • Anti-HBV therapy other than lamivudine (such as emtricitabine, lobucavir, entecavir, HBIG, clevudine, MCC-478) with the exception of interferon alpha, famciclovir or foscarnet that ended more than 12 weeks prior to screen.
  • Hepatic mass suggestive of hepatocellular carcinoma
  • Alpha-fetoprotein level greater than or equal to 200ng/mL
  • Evidence of gastrointestinal malabsorption or chronic nausea or vomiting
  • Current alcohol or substance abuse that potentially could interfere with patient compliance
  • Malignancy other than cutaneous Kaposi's sarcoma, skin cancer treated by resection or HPV-associated carcinoma in situ or Bowen's disease in the 5 years prior to enrollment
  • History of clinically significant renal dysfunction within the previous 12 months prior to baseline
  • Concomitant therapy with aminoglycosides, amphotericin B, cidofivir, cisplatinum, IV pentamidine, vancomycin, systemic chemotherapeutic agents, probenecid or other nephrotoxic agents
  • Proteinuria (greater than or equal to 3+)
  • ANA greater than or equal to 3 EU
  • Positive PCR test for hepatitis C
  • Antibodies to hepatitis D (delta hepatitis)
  • Pregnancy or breast-feeding
  • History of organ or bone marrow transplantation
  • Any systemic illness that will make it unlikely that the subject will be able to return to NIH for the required study visits.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institute of Allergy and Infectious Diseases (NIAID)

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Adefovir Dipivoxil for the Treatment of Hepatitis B in Human Immunodeficiency Virus Infected Patients With Decompensated Hepatitis B Liver Disease and a Hepatitis B Viral Load of at Least 1.0 X 10(6) (Copies/mL) Despite 52 Weeks of Lamivudine Therapy

This study will evaluate the safety and effectiveness of adding the experimental drug adefovir dipivoxil to lamivudine for treating hepatitis B virus (HBV) infection in HIV-infected patients with liver cirrhosis. Adefovir inhibits HBV by interfering with replication of the virus's genetic material. In some people, the drug has been active against strains of HBV that are resistant to lamivudine; it may also have some activity against HIV.

HIV-infected patients 21 years of age and older with chronic hepatitis B infection and liver cirrhosis who have received lamivudine treatment for at least 1 year may be eligible for this 48-week study. Candidates will be screened with a complete medical history, blood tests and a 24-hour urine collection. Blood tests include HLA typing (a test of genetic markers on white blood cells that permit specialized immunology studies). Within 4 weeks, candidates who appear eligible for the study will have a physical examination and medical history, an abdominal ultrasound (imaging test using sound waves) to check for cancer of the liver, chest X-ray and electrocardiogram (EKG). Blood and urine tests will also be done, and women who can become pregnant will have a pregnancy test.

Read more

Patients who meet the study criteria and decide to participate will then start treatment with one 10-mg adefovir pill per day by mouth. In addition, patients will continue to take all other medications prescribed by their doctor. Follow-up clinic visits will be scheduled as follows:

  • Days 1, 3, 5, 7, 10 and 21 - Blood will be drawn for specialized immunology tests and to measure blood levels of HIV and HBV.
  • Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44 - Blood and urine (single sample) tests will be done to determine the side effects of adefovir and its effect on the HBV infection.
  • Week 48 or early termination (end of study) - Blood tests (including tests for hepatitis C and D), abdominal ultrasound and a 24-hour urine collection to evaluate kidney function will be done.
  • Monthly visits beyond week 48 - Based on the HBV response to treatment and the availability of the drug from the sponsor, patients may be offered to extend their treatment with adefovir. Those who continue will have monthly follow-up visits for blood and urine (single sample) tests.
Read the detailed description

Patients co-infected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) who have advanced liver disease (decompensated cirrhosis by Child-Pugh score and no known cause of hepatitis other than HBV), a HBV viral load of at least 1 million copies/mL blood, and at least one year of therapy with lamivudine will be treated with open-label adefovir dipivoxil 10 mg daily and lamivudine 150 mg bid to evaluate the safety and efficacy of this regimen in this patient group and to obtain specimens for studies of immune responses to HBV in HIV-infected patients. Additionally the kinetics of viral load response to adefovir will be assessed. Specimens will be stored for possible use in evaluating HBV and HIV resistance to adefovir. L-carnitine supplementation will be used only if low serum carnitine levels are documented. Patients will be followed for HBV viral load response to adefovir for 48 weeks with possible extension. The primary study endpoints will be HBV viral load at week 24 (per-protocol patients) and DAVG at week 24 (intent-to-treat patients). Adefovir will be discontinued for toxicity; there will be no dose reduction. Up to 30 subjects will be enrolled.

Being tested
Adefovir
Keywords
Immunology, Cirrhosis, Ascites, Open-Label, Chronic, HIV, Hepatitis B
Medical subject headings
Hepatitis B, HIV Infections, Fibrosis, Ascites, Bronchiolitis Obliterans Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AdefovirDrug

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Mar 2001 (estimated)
  2. Study startMar 2001
  3. Study completionFeb 2004

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Enrolment
30 participants
IDs, dates and publications
ClinicalTrials.gov ID
NCT00013702
Sponsor's protocol ID
010134
Other IDs
01-I-0134
Status last verified
Feb 2004
First submitted
28 Mar 2001
Last updated
4 Mar 2008
Results posted
No

Publications

  • Colin JF, Cazals-Hatem D, Loriot MA, Martinot-Peignoux M, Pham BN, Auperin A, Degott C, Benhamou JP, Erlinger S, Valla D, Marcellin P. Influence of human immunodeficiency virus infection on chronic hepatitis B in homosexual men. Hepatology. 1999 Apr;29(4):1306-10. doi: 10.1002/hep.510290447.

    PubMed 10094979

  • Honkoop P, de Man RA, Niesters HG, Zondervan PE, Schalm SW. Acute exacerbation of chronic hepatitis B virus infection after withdrawal of lamivudine therapy. Hepatology. 2000 Sep;32(3):635-9. doi: 10.1053/jhep.2000.16333.

    PubMed 10960461

  • Lai CL, Chien RN, Leung NW, Chang TT, Guan R, Tai DI, Ng KY, Wu PC, Dent JC, Barber J, Stephenson SL, Gray DF. A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. N Engl J Med. 1998 Jul 9;339(2):61-8. doi: 10.1056/NEJM199807093390201.

    PubMed 9654535

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Adefovir in people with Hepatitis B and HIV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00013702, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.

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