Clinical Trial:Combination of Lamivudine and Adefovir Dipivoxil for Treatment of Chronic Hepatitis B

[Guest guest]

Combination of Lamivudine and Adefovir Dipivoxil for Treatment of Chronic

Hepatitis B

This study is currently recruiting patients.

Sponsored by

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Purpose

Aims: To assess the safety, antiviral activity and clinical benefit of the

combination of lamivudine and adefovir dipivoxil in patients with chronic

hepatitis B for up to five years.

Background: Adefovir dipivoxil and lamivudine are oral antiviral agents

that have been shown to have potent activity against HBV in vitro and in

vivo. Both drugs have been used extensively in patients with HIV infection

and more recently in controlled trials in patients with chronic hepatitis B.

While lamivudine monotherapy induces a transient improvement in viral levels

and liver histology, viral resistance develops in a large proportion of

patients with re-appearance of HBV DNA in serum in high levels associated

with mutations in the YMDD motif of the HBV polymerase gene and worsening of

the hepatitis.

Protocol: Up to 20 patients with HBeAg positive chronic hepatitis B who

have not been treated with nucleoside analogues for hepatitis B and who have

raised serum ALT levels, HBV DNA in serum (detectable on hybrid capture

assay or above 1.6 x 10(5) copies per ml by quantitative PCR) and active

liver disease on liver biopsy will be enrolled and started on the

combination of lamivudine (100 mg daily) and adefovir dipivoxil (10 mg

daily). Patients will be monitored carefully during the therapy for adverse

events, clinical symptoms and signs of liver disease, biochemical and

hematological parameters, and HBV serology at 2 to 4 week intervals. The

primary endpoint of therapy will be a maintained combined response (a

combination of virological, biochemical, and histological response).

Secondary endpoints will include loss of HBeAg, the individual types of

maintained responses (virological, biochemical and histological), the

development of resistance, and improvement in symptom scores and quality of

life assessments at 1 and 4 years. If patients demonstrate improvement at 1

year, therapy will be continued for up to five years with repeat evaluation

after 4 years.

Conclusions: This study will assess the effects of the combination of

lamivudine and adefovir dipivoxil in suppressing hepatitis B and prevention

of lamivudine resistant mutants that arise during long-term therapy with

lamivudine alone.

Condition Treatment or Intervention Phase

Sickle Cell Anemia

beta-Thalassemia

Pulmonary Hypertension Drug: Adefovir Dipivoxil Phase II

MEDLINEplus related topics: Anemia; High Blood Pressure; Sickle Cell

Anemia

Study Type: Interventional

Further Study Details:

Aims: To assess the safety, antiviral activity and clinical benefit of the

combination of lamivudine and adefovir dipivoxil in patients with chronic

hepatitis B for up to five years.

Background: Adefovir dipivoxil and lamivudine are oral antiviral agents

that have been shown to have potent activity against HBV in vitro and in

vivo. Both drugs have been used extensively in patients with HIV infection

and more recently in controlled trials in patients with chronic hepatitis B.

While lamivudine monotherapy induces a transient improvement in viral levels

and liver histology, viral resistance develops in a large proportion of

patients with re-appearance of HBV DNA in serum in high levels associated

with mutations in the YMDD motif of the HBV polymerase gene and worsening of

the hepatitis.

Protocol: Up to 20 patients with HBeAg positive chronic hepatitis B who

have not been treated with nucleoside analogues for hepatitis B and who have

raised serum ALT levels, HBV DNA in serum (detectable on hybrid capture

assay or above 1.6 x 10(5) copies per ml by quantitative PCR) and active

liver disease on liver biopsy will be enrolled and started on the

combination of lamivudine (100 mg daily) and adefovir dipivoxil (10 mg

daily). Patients will be monitored carefully during the therapy for adverse

events, clinical symptoms and signs of liver disease, biochemical and

hematological parameters, and HBV serology at 2 to 4 week intervals. The

primary endpoint of therapy will be a maintained combined response (a

combination of virological, biochemical, and histological response).

Secondary endpoints will include loss of HBeAg, the individual types of

maintained responses (virological, biochemical and histological), the

development of resistance, and improvement in symptom scores and quality of

life assessments at 1 and 4 years. If patients demonstrate improvement at 1

year, therapy will be continued for up to five years with repeat evaluation

after 4 years.

Conclusions: This study will assess the effects of the combination of

lamivudine and adefovir dipivoxil in suppressing hepatitis B and prevention

of lamivudine resistant mutants that arise during long-term therapy with

lamivudine alone.

Eligibility

Genders Eligible for Study: Both

Criteria

Must be 18 years and above, male or female.

Must have known serum HBsAg and HBeAg positivity for at least 6 months.

Must have detectable HBV-DNA in serum above 1.6 x 10(5) copies per ml, as

detected by hybrid capture assay or by quantitative PCR (Roche Cobas Assay).

Serum ALT or AST levels must be above the upper limit of normal based on

two determinations taken at least one month apart during the 6 months before

entry.

Liver biopsy within 1 year must be consistent with chronic hepatitis and

with a histology activity index score (HAI) of 6 or more (out of a total

possible score of 22) and an Ishak fibrosis score of at least 1 (out of a

total possible score of 6).

Must give written informed consent.

No previous or current treatment with lamivudine, adefovir, tenofovir, or

other nucleotide/nucleoside analogue known to be active against HBV.

No coinfection with HDV as defined by the presence of both anti-HDV in

serum and HDV antigen in liver.

No coinfection with HCV as defined by the presence of both anti-HCV and

HCV RNA in serum.

No coinfection with HIV as defined by the presence of anti-HIV in serum.

No decompensated liver disease as defined by serum bilirubin greater than

2.5 mg%, prothrombin time of greater than 2 seconds prolonged, a serum

albumin of less than 3.0 gm%, or a history of ascites, variceal bleeding, or

hepatic encephalopathy.

No presence of other causes of liver disease (i.e., hemochromatosis,

's disease, alcoholic liver disease, non-alcoholic steatohepatitis,

alpha-1 antitypsin deficiency).

Must not have a history of organ transplantation or in the absence of

organ transplantation, any immunosuppressive therapy requiring the use of

more than 5 mg of prednisone (or its equivalent) daily.

No significant systemic illnesses other than liver diseases including

congestive heart failure, renal failure, chronic pancreatitis, diabetes

mellitus with poor control that in the opinion of the investigators might

interfere with therapy.

Must not be pregnant or have the inability to practice contraception in

patients capable of bearing or fathering children.

No pre-existing bone marrow suppression: WBC less than 2,000 cells/mm(3),

hematocrit less than 30%, or platelets less than 50,000 cells/mm(3).

No history of clinically apparent pancreatitis or evidence of subclinical

pancreatitis as shown by serum amylase values twice the upper limits of the

normal range and abnormalities of the pancreas on CT or other imaging

studies of the abdomen.

No prior interferon treatment within 1 year of entry.

No sensory or motor neuropathy apparent from medical history and physical

examination.

No creatinine clearance less than 50 ml/min or serum creatinine greater

than 1.5 mg/dl; creatinine clearance will be determined on a 24 hour urine

specimen. Accuracy of collection will be ensured by documenting appropriate

total creatinine excretion in the 24 hour urine specimen (15 mg/kg) and

correcting for the patient's age and gender.

No concurrent use of nephrotoxic agents (e.g., aminoglycosides,

amphotericin B, vancomycin, foscarnet, cis-platnum, pentamidine,

nonsteroidal anti-inflammatory agents) or competitors of renal tubular

excretion (e.g., probenecid) within 2 months prior to study screening or the

expectation that the subject will receive these during the course of the

study.

No history of hypersensitivity to nucleoside/nucleotide analogues.

No active ethanol/drug abuse/psychiatric problems that, in the

investigator's opinion, might interfere with participation in the study.

No history of seizure disorder.

No history of renal tubular acidosis.

No history of malignancy or treatment for a malignancy within the past 5

years.

Expected Total Enrollment: 20

Location and Contact Information

land

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),

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

Long-term follow-up of HBeAg-positive patients treated with interferon alfa

for chronic hepatitis B

Chronic hepatitis B virus infection: treatment strategies for the next

millennium

The treatment of chronic viral hepatitis

Study ID Numbers 010246; 01-DK-0246

Date study started August 28, 2001

Record last reviewed August 20, 2001

Last Updated August 20, 2001

NLM Identifier NCT00023309

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

[Guest guest]

Combination of Lamivudine and Adefovir Dipivoxil for Treatment of Chronic

Hepatitis B

This study is currently recruiting patients.

Sponsored by

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Purpose

Aims: To assess the safety, antiviral activity and clinical benefit of the

combination of lamivudine and adefovir dipivoxil in patients with chronic

hepatitis B for up to five years.

Background: Adefovir dipivoxil and lamivudine are oral antiviral agents

that have been shown to have potent activity against HBV in vitro and in

vivo. Both drugs have been used extensively in patients with HIV infection

and more recently in controlled trials in patients with chronic hepatitis B.

While lamivudine monotherapy induces a transient improvement in viral levels

and liver histology, viral resistance develops in a large proportion of

patients with re-appearance of HBV DNA in serum in high levels associated

with mutations in the YMDD motif of the HBV polymerase gene and worsening of

the hepatitis.

Protocol: Up to 20 patients with HBeAg positive chronic hepatitis B who

have not been treated with nucleoside analogues for hepatitis B and who have

raised serum ALT levels, HBV DNA in serum (detectable on hybrid capture

assay or above 1.6 x 10(5) copies per ml by quantitative PCR) and active

liver disease on liver biopsy will be enrolled and started on the

combination of lamivudine (100 mg daily) and adefovir dipivoxil (10 mg

daily). Patients will be monitored carefully during the therapy for adverse

events, clinical symptoms and signs of liver disease, biochemical and

hematological parameters, and HBV serology at 2 to 4 week intervals. The

primary endpoint of therapy will be a maintained combined response (a

combination of virological, biochemical, and histological response).

Secondary endpoints will include loss of HBeAg, the individual types of

maintained responses (virological, biochemical and histological), the

development of resistance, and improvement in symptom scores and quality of

life assessments at 1 and 4 years. If patients demonstrate improvement at 1

year, therapy will be continued for up to five years with repeat evaluation

after 4 years.

Conclusions: This study will assess the effects of the combination of

lamivudine and adefovir dipivoxil in suppressing hepatitis B and prevention

of lamivudine resistant mutants that arise during long-term therapy with

lamivudine alone.

Condition Treatment or Intervention Phase

Sickle Cell Anemia

beta-Thalassemia

Pulmonary Hypertension Drug: Adefovir Dipivoxil Phase II

MEDLINEplus related topics: Anemia; High Blood Pressure; Sickle Cell

Anemia

Study Type: Interventional

Further Study Details:

Aims: To assess the safety, antiviral activity and clinical benefit of the

combination of lamivudine and adefovir dipivoxil in patients with chronic

hepatitis B for up to five years.

Background: Adefovir dipivoxil and lamivudine are oral antiviral agents

that have been shown to have potent activity against HBV in vitro and in

vivo. Both drugs have been used extensively in patients with HIV infection

and more recently in controlled trials in patients with chronic hepatitis B.

While lamivudine monotherapy induces a transient improvement in viral levels

and liver histology, viral resistance develops in a large proportion of

patients with re-appearance of HBV DNA in serum in high levels associated

with mutations in the YMDD motif of the HBV polymerase gene and worsening of

the hepatitis.

Protocol: Up to 20 patients with HBeAg positive chronic hepatitis B who

have not been treated with nucleoside analogues for hepatitis B and who have

raised serum ALT levels, HBV DNA in serum (detectable on hybrid capture

assay or above 1.6 x 10(5) copies per ml by quantitative PCR) and active

liver disease on liver biopsy will be enrolled and started on the

combination of lamivudine (100 mg daily) and adefovir dipivoxil (10 mg

daily). Patients will be monitored carefully during the therapy for adverse

events, clinical symptoms and signs of liver disease, biochemical and

hematological parameters, and HBV serology at 2 to 4 week intervals. The

primary endpoint of therapy will be a maintained combined response (a

combination of virological, biochemical, and histological response).

Secondary endpoints will include loss of HBeAg, the individual types of

maintained responses (virological, biochemical and histological), the

development of resistance, and improvement in symptom scores and quality of

life assessments at 1 and 4 years. If patients demonstrate improvement at 1

year, therapy will be continued for up to five years with repeat evaluation

after 4 years.

Conclusions: This study will assess the effects of the combination of

lamivudine and adefovir dipivoxil in suppressing hepatitis B and prevention

of lamivudine resistant mutants that arise during long-term therapy with

lamivudine alone.

Eligibility

Genders Eligible for Study: Both

Criteria

Must be 18 years and above, male or female.

Must have known serum HBsAg and HBeAg positivity for at least 6 months.

Must have detectable HBV-DNA in serum above 1.6 x 10(5) copies per ml, as

detected by hybrid capture assay or by quantitative PCR (Roche Cobas Assay).

Serum ALT or AST levels must be above the upper limit of normal based on

two determinations taken at least one month apart during the 6 months before

entry.

Liver biopsy within 1 year must be consistent with chronic hepatitis and

with a histology activity index score (HAI) of 6 or more (out of a total

possible score of 22) and an Ishak fibrosis score of at least 1 (out of a

total possible score of 6).

Must give written informed consent.

No previous or current treatment with lamivudine, adefovir, tenofovir, or

other nucleotide/nucleoside analogue known to be active against HBV.

No coinfection with HDV as defined by the presence of both anti-HDV in

serum and HDV antigen in liver.

No coinfection with HCV as defined by the presence of both anti-HCV and

HCV RNA in serum.

No coinfection with HIV as defined by the presence of anti-HIV in serum.

No decompensated liver disease as defined by serum bilirubin greater than

2.5 mg%, prothrombin time of greater than 2 seconds prolonged, a serum

albumin of less than 3.0 gm%, or a history of ascites, variceal bleeding, or

hepatic encephalopathy.

No presence of other causes of liver disease (i.e., hemochromatosis,

's disease, alcoholic liver disease, non-alcoholic steatohepatitis,

alpha-1 antitypsin deficiency).

Must not have a history of organ transplantation or in the absence of

organ transplantation, any immunosuppressive therapy requiring the use of

more than 5 mg of prednisone (or its equivalent) daily.

No significant systemic illnesses other than liver diseases including

congestive heart failure, renal failure, chronic pancreatitis, diabetes

mellitus with poor control that in the opinion of the investigators might

interfere with therapy.

Must not be pregnant or have the inability to practice contraception in

patients capable of bearing or fathering children.

No pre-existing bone marrow suppression: WBC less than 2,000 cells/mm(3),

hematocrit less than 30%, or platelets less than 50,000 cells/mm(3).

No history of clinically apparent pancreatitis or evidence of subclinical

pancreatitis as shown by serum amylase values twice the upper limits of the

normal range and abnormalities of the pancreas on CT or other imaging

studies of the abdomen.

No prior interferon treatment within 1 year of entry.

No sensory or motor neuropathy apparent from medical history and physical

examination.

No creatinine clearance less than 50 ml/min or serum creatinine greater

than 1.5 mg/dl; creatinine clearance will be determined on a 24 hour urine

specimen. Accuracy of collection will be ensured by documenting appropriate

total creatinine excretion in the 24 hour urine specimen (15 mg/kg) and

correcting for the patient's age and gender.

No concurrent use of nephrotoxic agents (e.g., aminoglycosides,

amphotericin B, vancomycin, foscarnet, cis-platnum, pentamidine,

nonsteroidal anti-inflammatory agents) or competitors of renal tubular

excretion (e.g., probenecid) within 2 months prior to study screening or the

expectation that the subject will receive these during the course of the

study.

No history of hypersensitivity to nucleoside/nucleotide analogues.

No active ethanol/drug abuse/psychiatric problems that, in the

investigator's opinion, might interfere with participation in the study.

No history of seizure disorder.

No history of renal tubular acidosis.

No history of malignancy or treatment for a malignancy within the past 5

years.

Expected Total Enrollment: 20

Location and Contact Information

land

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),

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

Long-term follow-up of HBeAg-positive patients treated with interferon alfa

for chronic hepatitis B

Chronic hepatitis B virus infection: treatment strategies for the next

millennium

The treatment of chronic viral hepatitis

Study ID Numbers 010246; 01-DK-0246

Date study started August 28, 2001

Record last reviewed August 20, 2001

Last Updated August 20, 2001

NLM Identifier NCT00023309

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

[Guest guest]

Combination of Lamivudine and Adefovir Dipivoxil for Treatment of Chronic

Hepatitis B

This study is currently recruiting patients.

Sponsored by

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Purpose

Aims: To assess the safety, antiviral activity and clinical benefit of the

combination of lamivudine and adefovir dipivoxil in patients with chronic

hepatitis B for up to five years.

Background: Adefovir dipivoxil and lamivudine are oral antiviral agents

that have been shown to have potent activity against HBV in vitro and in

vivo. Both drugs have been used extensively in patients with HIV infection

and more recently in controlled trials in patients with chronic hepatitis B.

While lamivudine monotherapy induces a transient improvement in viral levels

and liver histology, viral resistance develops in a large proportion of

patients with re-appearance of HBV DNA in serum in high levels associated

with mutations in the YMDD motif of the HBV polymerase gene and worsening of

the hepatitis.

Protocol: Up to 20 patients with HBeAg positive chronic hepatitis B who

have not been treated with nucleoside analogues for hepatitis B and who have

raised serum ALT levels, HBV DNA in serum (detectable on hybrid capture

assay or above 1.6 x 10(5) copies per ml by quantitative PCR) and active

liver disease on liver biopsy will be enrolled and started on the

combination of lamivudine (100 mg daily) and adefovir dipivoxil (10 mg

daily). Patients will be monitored carefully during the therapy for adverse

events, clinical symptoms and signs of liver disease, biochemical and

hematological parameters, and HBV serology at 2 to 4 week intervals. The

primary endpoint of therapy will be a maintained combined response (a

combination of virological, biochemical, and histological response).

Secondary endpoints will include loss of HBeAg, the individual types of

maintained responses (virological, biochemical and histological), the

development of resistance, and improvement in symptom scores and quality of

life assessments at 1 and 4 years. If patients demonstrate improvement at 1

year, therapy will be continued for up to five years with repeat evaluation

after 4 years.

Conclusions: This study will assess the effects of the combination of

lamivudine and adefovir dipivoxil in suppressing hepatitis B and prevention

of lamivudine resistant mutants that arise during long-term therapy with

lamivudine alone.

Condition Treatment or Intervention Phase

Sickle Cell Anemia

beta-Thalassemia

Pulmonary Hypertension Drug: Adefovir Dipivoxil Phase II

MEDLINEplus related topics: Anemia; High Blood Pressure; Sickle Cell

Anemia

Study Type: Interventional

Further Study Details:

Aims: To assess the safety, antiviral activity and clinical benefit of the

combination of lamivudine and adefovir dipivoxil in patients with chronic

hepatitis B for up to five years.

Background: Adefovir dipivoxil and lamivudine are oral antiviral agents

that have been shown to have potent activity against HBV in vitro and in

vivo. Both drugs have been used extensively in patients with HIV infection

and more recently in controlled trials in patients with chronic hepatitis B.

While lamivudine monotherapy induces a transient improvement in viral levels

and liver histology, viral resistance develops in a large proportion of

patients with re-appearance of HBV DNA in serum in high levels associated

with mutations in the YMDD motif of the HBV polymerase gene and worsening of

the hepatitis.

Protocol: Up to 20 patients with HBeAg positive chronic hepatitis B who

have not been treated with nucleoside analogues for hepatitis B and who have

raised serum ALT levels, HBV DNA in serum (detectable on hybrid capture

assay or above 1.6 x 10(5) copies per ml by quantitative PCR) and active

liver disease on liver biopsy will be enrolled and started on the

combination of lamivudine (100 mg daily) and adefovir dipivoxil (10 mg

daily). Patients will be monitored carefully during the therapy for adverse

events, clinical symptoms and signs of liver disease, biochemical and

hematological parameters, and HBV serology at 2 to 4 week intervals. The

primary endpoint of therapy will be a maintained combined response (a

combination of virological, biochemical, and histological response).

Secondary endpoints will include loss of HBeAg, the individual types of

maintained responses (virological, biochemical and histological), the

development of resistance, and improvement in symptom scores and quality of

life assessments at 1 and 4 years. If patients demonstrate improvement at 1

year, therapy will be continued for up to five years with repeat evaluation

after 4 years.

Conclusions: This study will assess the effects of the combination of

lamivudine and adefovir dipivoxil in suppressing hepatitis B and prevention

of lamivudine resistant mutants that arise during long-term therapy with

lamivudine alone.

Eligibility

Genders Eligible for Study: Both

Criteria

Must be 18 years and above, male or female.

Must have known serum HBsAg and HBeAg positivity for at least 6 months.

Must have detectable HBV-DNA in serum above 1.6 x 10(5) copies per ml, as

detected by hybrid capture assay or by quantitative PCR (Roche Cobas Assay).

Serum ALT or AST levels must be above the upper limit of normal based on

two determinations taken at least one month apart during the 6 months before

entry.

Liver biopsy within 1 year must be consistent with chronic hepatitis and

with a histology activity index score (HAI) of 6 or more (out of a total

possible score of 22) and an Ishak fibrosis score of at least 1 (out of a

total possible score of 6).

Must give written informed consent.

No previous or current treatment with lamivudine, adefovir, tenofovir, or

other nucleotide/nucleoside analogue known to be active against HBV.

No coinfection with HDV as defined by the presence of both anti-HDV in

serum and HDV antigen in liver.

No coinfection with HCV as defined by the presence of both anti-HCV and

HCV RNA in serum.

No coinfection with HIV as defined by the presence of anti-HIV in serum.

No decompensated liver disease as defined by serum bilirubin greater than

2.5 mg%, prothrombin time of greater than 2 seconds prolonged, a serum

albumin of less than 3.0 gm%, or a history of ascites, variceal bleeding, or

hepatic encephalopathy.

No presence of other causes of liver disease (i.e., hemochromatosis,

's disease, alcoholic liver disease, non-alcoholic steatohepatitis,

alpha-1 antitypsin deficiency).

Must not have a history of organ transplantation or in the absence of

organ transplantation, any immunosuppressive therapy requiring the use of

more than 5 mg of prednisone (or its equivalent) daily.

No significant systemic illnesses other than liver diseases including

congestive heart failure, renal failure, chronic pancreatitis, diabetes

mellitus with poor control that in the opinion of the investigators might

interfere with therapy.

Must not be pregnant or have the inability to practice contraception in

patients capable of bearing or fathering children.

No pre-existing bone marrow suppression: WBC less than 2,000 cells/mm(3),

hematocrit less than 30%, or platelets less than 50,000 cells/mm(3).

No history of clinically apparent pancreatitis or evidence of subclinical

pancreatitis as shown by serum amylase values twice the upper limits of the

normal range and abnormalities of the pancreas on CT or other imaging

studies of the abdomen.

No prior interferon treatment within 1 year of entry.

No sensory or motor neuropathy apparent from medical history and physical

examination.

No creatinine clearance less than 50 ml/min or serum creatinine greater

than 1.5 mg/dl; creatinine clearance will be determined on a 24 hour urine

specimen. Accuracy of collection will be ensured by documenting appropriate

total creatinine excretion in the 24 hour urine specimen (15 mg/kg) and

correcting for the patient's age and gender.

No concurrent use of nephrotoxic agents (e.g., aminoglycosides,

amphotericin B, vancomycin, foscarnet, cis-platnum, pentamidine,

nonsteroidal anti-inflammatory agents) or competitors of renal tubular

excretion (e.g., probenecid) within 2 months prior to study screening or the

expectation that the subject will receive these during the course of the

study.

No history of hypersensitivity to nucleoside/nucleotide analogues.

No active ethanol/drug abuse/psychiatric problems that, in the

investigator's opinion, might interfere with participation in the study.

No history of seizure disorder.

No history of renal tubular acidosis.

No history of malignancy or treatment for a malignancy within the past 5

years.

Expected Total Enrollment: 20

Location and Contact Information

land

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),

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

Long-term follow-up of HBeAg-positive patients treated with interferon alfa

for chronic hepatitis B

Chronic hepatitis B virus infection: treatment strategies for the next

millennium

The treatment of chronic viral hepatitis

Study ID Numbers 010246; 01-DK-0246

Date study started August 28, 2001

Record last reviewed August 20, 2001

Last Updated August 20, 2001

NLM Identifier NCT00023309

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

[Guest guest]

Combination of Lamivudine and Adefovir Dipivoxil for Treatment of Chronic

Hepatitis B

This study is currently recruiting patients.

Sponsored by

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Purpose

Aims: To assess the safety, antiviral activity and clinical benefit of the

combination of lamivudine and adefovir dipivoxil in patients with chronic

hepatitis B for up to five years.

Background: Adefovir dipivoxil and lamivudine are oral antiviral agents

that have been shown to have potent activity against HBV in vitro and in

vivo. Both drugs have been used extensively in patients with HIV infection

and more recently in controlled trials in patients with chronic hepatitis B.

While lamivudine monotherapy induces a transient improvement in viral levels

and liver histology, viral resistance develops in a large proportion of

patients with re-appearance of HBV DNA in serum in high levels associated

with mutations in the YMDD motif of the HBV polymerase gene and worsening of

the hepatitis.

Protocol: Up to 20 patients with HBeAg positive chronic hepatitis B who

have not been treated with nucleoside analogues for hepatitis B and who have

raised serum ALT levels, HBV DNA in serum (detectable on hybrid capture

assay or above 1.6 x 10(5) copies per ml by quantitative PCR) and active

liver disease on liver biopsy will be enrolled and started on the

combination of lamivudine (100 mg daily) and adefovir dipivoxil (10 mg

daily). Patients will be monitored carefully during the therapy for adverse

events, clinical symptoms and signs of liver disease, biochemical and

hematological parameters, and HBV serology at 2 to 4 week intervals. The

primary endpoint of therapy will be a maintained combined response (a

combination of virological, biochemical, and histological response).

Secondary endpoints will include loss of HBeAg, the individual types of

maintained responses (virological, biochemical and histological), the

development of resistance, and improvement in symptom scores and quality of

life assessments at 1 and 4 years. If patients demonstrate improvement at 1

year, therapy will be continued for up to five years with repeat evaluation

after 4 years.

Conclusions: This study will assess the effects of the combination of

lamivudine and adefovir dipivoxil in suppressing hepatitis B and prevention

of lamivudine resistant mutants that arise during long-term therapy with

lamivudine alone.

Condition Treatment or Intervention Phase

Sickle Cell Anemia

beta-Thalassemia

Pulmonary Hypertension Drug: Adefovir Dipivoxil Phase II

MEDLINEplus related topics: Anemia; High Blood Pressure; Sickle Cell

Anemia

Study Type: Interventional

Further Study Details:

Aims: To assess the safety, antiviral activity and clinical benefit of the

combination of lamivudine and adefovir dipivoxil in patients with chronic

hepatitis B for up to five years.

Background: Adefovir dipivoxil and lamivudine are oral antiviral agents

that have been shown to have potent activity against HBV in vitro and in

vivo. Both drugs have been used extensively in patients with HIV infection

and more recently in controlled trials in patients with chronic hepatitis B.

While lamivudine monotherapy induces a transient improvement in viral levels

and liver histology, viral resistance develops in a large proportion of

patients with re-appearance of HBV DNA in serum in high levels associated

with mutations in the YMDD motif of the HBV polymerase gene and worsening of

the hepatitis.

Protocol: Up to 20 patients with HBeAg positive chronic hepatitis B who

have not been treated with nucleoside analogues for hepatitis B and who have

raised serum ALT levels, HBV DNA in serum (detectable on hybrid capture

assay or above 1.6 x 10(5) copies per ml by quantitative PCR) and active

liver disease on liver biopsy will be enrolled and started on the

combination of lamivudine (100 mg daily) and adefovir dipivoxil (10 mg

daily). Patients will be monitored carefully during the therapy for adverse

events, clinical symptoms and signs of liver disease, biochemical and

hematological parameters, and HBV serology at 2 to 4 week intervals. The

primary endpoint of therapy will be a maintained combined response (a

combination of virological, biochemical, and histological response).

Secondary endpoints will include loss of HBeAg, the individual types of

maintained responses (virological, biochemical and histological), the

development of resistance, and improvement in symptom scores and quality of

life assessments at 1 and 4 years. If patients demonstrate improvement at 1

year, therapy will be continued for up to five years with repeat evaluation

after 4 years.

Conclusions: This study will assess the effects of the combination of

lamivudine and adefovir dipivoxil in suppressing hepatitis B and prevention

of lamivudine resistant mutants that arise during long-term therapy with

lamivudine alone.

Eligibility

Genders Eligible for Study: Both

Criteria

Must be 18 years and above, male or female.

Must have known serum HBsAg and HBeAg positivity for at least 6 months.

Must have detectable HBV-DNA in serum above 1.6 x 10(5) copies per ml, as

detected by hybrid capture assay or by quantitative PCR (Roche Cobas Assay).

Serum ALT or AST levels must be above the upper limit of normal based on

two determinations taken at least one month apart during the 6 months before

entry.

Liver biopsy within 1 year must be consistent with chronic hepatitis and

with a histology activity index score (HAI) of 6 or more (out of a total

possible score of 22) and an Ishak fibrosis score of at least 1 (out of a

total possible score of 6).

Must give written informed consent.

No previous or current treatment with lamivudine, adefovir, tenofovir, or

other nucleotide/nucleoside analogue known to be active against HBV.

No coinfection with HDV as defined by the presence of both anti-HDV in

serum and HDV antigen in liver.

No coinfection with HCV as defined by the presence of both anti-HCV and

HCV RNA in serum.

No coinfection with HIV as defined by the presence of anti-HIV in serum.

No decompensated liver disease as defined by serum bilirubin greater than

2.5 mg%, prothrombin time of greater than 2 seconds prolonged, a serum

albumin of less than 3.0 gm%, or a history of ascites, variceal bleeding, or

hepatic encephalopathy.

No presence of other causes of liver disease (i.e., hemochromatosis,

's disease, alcoholic liver disease, non-alcoholic steatohepatitis,

alpha-1 antitypsin deficiency).

Must not have a history of organ transplantation or in the absence of

organ transplantation, any immunosuppressive therapy requiring the use of

more than 5 mg of prednisone (or its equivalent) daily.

No significant systemic illnesses other than liver diseases including

congestive heart failure, renal failure, chronic pancreatitis, diabetes

mellitus with poor control that in the opinion of the investigators might

interfere with therapy.

Must not be pregnant or have the inability to practice contraception in

patients capable of bearing or fathering children.

No pre-existing bone marrow suppression: WBC less than 2,000 cells/mm(3),

hematocrit less than 30%, or platelets less than 50,000 cells/mm(3).

No history of clinically apparent pancreatitis or evidence of subclinical

pancreatitis as shown by serum amylase values twice the upper limits of the

normal range and abnormalities of the pancreas on CT or other imaging

studies of the abdomen.

No prior interferon treatment within 1 year of entry.

No sensory or motor neuropathy apparent from medical history and physical

examination.

No creatinine clearance less than 50 ml/min or serum creatinine greater

than 1.5 mg/dl; creatinine clearance will be determined on a 24 hour urine

specimen. Accuracy of collection will be ensured by documenting appropriate

total creatinine excretion in the 24 hour urine specimen (15 mg/kg) and

correcting for the patient's age and gender.

No concurrent use of nephrotoxic agents (e.g., aminoglycosides,

amphotericin B, vancomycin, foscarnet, cis-platnum, pentamidine,

nonsteroidal anti-inflammatory agents) or competitors of renal tubular

excretion (e.g., probenecid) within 2 months prior to study screening or the

expectation that the subject will receive these during the course of the

study.

No history of hypersensitivity to nucleoside/nucleotide analogues.

No active ethanol/drug abuse/psychiatric problems that, in the

investigator's opinion, might interfere with participation in the study.

No history of seizure disorder.

No history of renal tubular acidosis.

No history of malignancy or treatment for a malignancy within the past 5

years.

Expected Total Enrollment: 20

Location and Contact Information

land

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),

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

Long-term follow-up of HBeAg-positive patients treated with interferon alfa

for chronic hepatitis B

Chronic hepatitis B virus infection: treatment strategies for the next

millennium

The treatment of chronic viral hepatitis

Study ID Numbers 010246; 01-DK-0246

Date study started August 28, 2001

Record last reviewed August 20, 2001

Last Updated August 20, 2001

NLM Identifier NCT00023309

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