Adefovir Dipivoxil to Treat Hepatitis B in HIV-Infected Patients

NCT00013702 | Completed Phase 2

• 2 other identifiers: 01013401-I-0134
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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. 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.

Conditions

Hepatitis B; HIV Infection

Keywords

Immunology; Cirrhosis; Ascites; Open-Label; Chronic; HIV; Hepatitis B

Interventions

Adefovir DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institute of Allergy and Infectious Diseases (NIAID)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 10094979 BACKGROUND

• 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.

  PMID: 10960461 BACKGROUND

• 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.

  PMID: 9654535 BACKGROUND

MeSH Terms

Conditions

Hepatitis B; HIV Infections; Fibrosis; Ascites; Bronchiolitis Obliterans Syndrome

Interventions

adefovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: March 28, 2001
• First Posted: March 29, 2001
• Study Start: March 1, 2001
• Study Completion: February 1, 2004
• Last Updated: March 4, 2008

Record last verified: 2004-02

Locations

US (1)