Clinical Trial:Adefovir Dipivoxil to Treat Hepatitis B in HIV-Infected Patients

[Guest guest]

Adefovir Dipivoxil to Treat Hepatitis B in HIV-Infected Patients

This study is currently recruiting patients.

Sponsored by

National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

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.

Condition Treatment or Intervention Phase

Hepatitis B

HIV Infection Drug: Adefovir dipivoxil Phase II

MEDLINEplus related topics: AIDS; Hepatitis; Viral Infections

Study Type: Interventional

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

Further Study Details:

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.

Eligibility

Genders Eligible for Study: Both

Criteria

Must be at least 21 years of age.

Must have infection with HBV with HBV viral load of at least 1.0 x 10(6)

copies/mL by Roche assay at screen.

Must be 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.

Must have a physician(s) outside of NIH who will provide routine, as well

as HIV and liver specific, care.

Must be 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 month prior to study entry).

Serum creatinine must be less than 1.5 mg/dL.

Serum phosphorus of at least 2.2 mg/dL (normal range NIH 2.3-4.3 mg/dL).

Neutrophil count must be equal to or greater than 1000 cells/mm(3).

Platelets must be at least 50,000/mm(3).

Hemoglobin must be at least 8.0 mg/dL.

ALT must be less than or equal to 287(7 X the NIH upper limit of normal).

Must not be pregnant or breast-feeding. Pregnancy test must be negative

within two weeks prior to dosing with study medications.

If capable of pregnancy, effective contraception must be used. Effective

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 regiment that will not alter metabolism of

hormonal contraception.

Must be willing and able to provide written informed consent.

Because liver disease can result in encephalopathy, patient must be

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.

Must not have prior use of ADV (outside of patient receiving adefovir from

NIH under emergency use IND) or prior use of tenofovir, or cidofovir.

Must not have active serious systemic infections other than HIV or HBV.

Must not have liver disease caused by reasons other than hepatitis B e.g.,

HCV, HDV, 's hemochromatosis, autoimmune hepatitis (ANA of greater

than or equal to 160) except history of drug-associated hepatitis with

discontinuation of causative agent.

Must not have a history of clinically significant pancreatitis.

Must not have a history of significant encephalopathy.

Must not have a history of untreated varices.

Must not have a new AIDS-defining event other than esophageal candidiasis

diagnoses within one month prior to baseline.

Must not have decompensated heart failure.

Must not have 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.

Must not be under 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.

Must not have a hepatic mass suggestive of hepatocellular carcinoma.

Must not have a alpha-fetoprotein level greater than or equal to 200ng/mL.

Must not have evidence of gastrointestinal malabsorption or chronic nausea

or vomiting.

Must not have current alcohol or substance abuse that potentially could

interfere with patient compliance.

Must not have 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.

Must not have a history of clinically significant renal dysfunction within

the previous 12 months prior to baseline.

Must not have concomitant therapy with aminoglycosides, amphotericin B,

cidofivir, cisplatinum, IV pentamidine, vancomycin, systemic

chemotherapeutic agents, probenecid or other nephrotoxic agents.

Must not have a proteinuria greater than or equal to 3+.

Must not have ANA greater than or equal to 1:160.

Must not have a positive PCR test for hepatitis C.

Must not have antibodies to hepatitis D (delta hepatitis).

Must not be pregnant or breast-feeding.

Must not have a history of organ or bone marrow transplantation.

Must not have any systemic illness that will make in unlikely that the

subject will be able to return to NIH for the required study visits.

Must not have active seizure disorder.

Expected Total Enrollment: 30

Location and Contact Information

land

National Institute of Allergy and Infectious Diseases (NIAID), 9000

Rockville Pike Bethesda, land, 20892, United States; Recruiting

Patient Recruitment and Public Liaison Office 1-800-411-1222

prpl@...

TTY 1-866-411-1010

More Information

Detailed Web Page

Publications

The influence of human immunodeficiency virus infection of chronic hepatitis

B in homosexual men

Acute exacerbation of chronic hepatitis B virus infection after withdrawal

of lamivudine therapy

A one year trial of lamivudine for chronic hepatitis B Asia hepatitis

lamivudine study group

Study ID Numbers 010134; 01-I-0134

Date study started March 21, 2001

Record last reviewed March 12, 2001

Last Updated March 12, 2001

NLM Identifier NCT00013702

ClinicalTrials.gov processed this record on 2001-12-26

Hugs,

Sheree

[Guest guest]

Adefovir Dipivoxil to Treat Hepatitis B in HIV-Infected Patients

This study is currently recruiting patients.

Sponsored by

National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

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.

Condition Treatment or Intervention Phase

Hepatitis B

HIV Infection Drug: Adefovir dipivoxil Phase II

MEDLINEplus related topics: AIDS; Hepatitis; Viral Infections

Study Type: Interventional

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

Further Study Details:

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.

Eligibility

Genders Eligible for Study: Both

Criteria

Must be at least 21 years of age.

Must have infection with HBV with HBV viral load of at least 1.0 x 10(6)

copies/mL by Roche assay at screen.

Must be 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.

Must have a physician(s) outside of NIH who will provide routine, as well

as HIV and liver specific, care.

Must be 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 month prior to study entry).

Serum creatinine must be less than 1.5 mg/dL.

Serum phosphorus of at least 2.2 mg/dL (normal range NIH 2.3-4.3 mg/dL).

Neutrophil count must be equal to or greater than 1000 cells/mm(3).

Platelets must be at least 50,000/mm(3).

Hemoglobin must be at least 8.0 mg/dL.

ALT must be less than or equal to 287(7 X the NIH upper limit of normal).

Must not be pregnant or breast-feeding. Pregnancy test must be negative

within two weeks prior to dosing with study medications.

If capable of pregnancy, effective contraception must be used. Effective

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 regiment that will not alter metabolism of

hormonal contraception.

Must be willing and able to provide written informed consent.

Because liver disease can result in encephalopathy, patient must be

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.

Must not have prior use of ADV (outside of patient receiving adefovir from

NIH under emergency use IND) or prior use of tenofovir, or cidofovir.

Must not have active serious systemic infections other than HIV or HBV.

Must not have liver disease caused by reasons other than hepatitis B e.g.,

HCV, HDV, 's hemochromatosis, autoimmune hepatitis (ANA of greater

than or equal to 160) except history of drug-associated hepatitis with

discontinuation of causative agent.

Must not have a history of clinically significant pancreatitis.

Must not have a history of significant encephalopathy.

Must not have a history of untreated varices.

Must not have a new AIDS-defining event other than esophageal candidiasis

diagnoses within one month prior to baseline.

Must not have decompensated heart failure.

Must not have 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.

Must not be under 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.

Must not have a hepatic mass suggestive of hepatocellular carcinoma.

Must not have a alpha-fetoprotein level greater than or equal to 200ng/mL.

Must not have evidence of gastrointestinal malabsorption or chronic nausea

or vomiting.

Must not have current alcohol or substance abuse that potentially could

interfere with patient compliance.

Must not have 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.

Must not have a history of clinically significant renal dysfunction within

the previous 12 months prior to baseline.

Must not have concomitant therapy with aminoglycosides, amphotericin B,

cidofivir, cisplatinum, IV pentamidine, vancomycin, systemic

chemotherapeutic agents, probenecid or other nephrotoxic agents.

Must not have a proteinuria greater than or equal to 3+.

Must not have ANA greater than or equal to 1:160.

Must not have a positive PCR test for hepatitis C.

Must not have antibodies to hepatitis D (delta hepatitis).

Must not be pregnant or breast-feeding.

Must not have a history of organ or bone marrow transplantation.

Must not have any systemic illness that will make in unlikely that the

subject will be able to return to NIH for the required study visits.

Must not have active seizure disorder.

Expected Total Enrollment: 30

Location and Contact Information

land

National Institute of Allergy and Infectious Diseases (NIAID), 9000

Rockville Pike Bethesda, land, 20892, United States; Recruiting

Patient Recruitment and Public Liaison Office 1-800-411-1222

prpl@...

TTY 1-866-411-1010

More Information

Detailed Web Page

Publications

The influence of human immunodeficiency virus infection of chronic hepatitis

B in homosexual men

Acute exacerbation of chronic hepatitis B virus infection after withdrawal

of lamivudine therapy

A one year trial of lamivudine for chronic hepatitis B Asia hepatitis

lamivudine study group

Study ID Numbers 010134; 01-I-0134

Date study started March 21, 2001

Record last reviewed March 12, 2001

Last Updated March 12, 2001

NLM Identifier NCT00013702

ClinicalTrials.gov processed this record on 2001-12-26

Hugs,

Sheree