Tenofovir Alone Versus Tenofovir With Emtricitabine to Treat Chronic Hepatitis B

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00524173
• Date of registration: 31/08/2007
• Primary sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Public title: Tenofovir Alone Versus Tenofovir With Emtricitabine to Treat Chronic Hepatitis B
• Scientific title: Tenofovir Disoproxil Fumarate Alone Versus Its Combination With Emtricitabine for Treatment of Chronic Hepatitis B
• Date of first enrolment: August 2007
• Target sample size: 100
• Recruitment status: Recruiting
• URL: http://clinicaltrials.gov/show/NCT00524173
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)

• Name: Elenita Rivera, R.N.

• Name: Marc G Ghany, M.D.
• Affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Key inclusion & exclusion criteria

- INCLUSION CRITERIA (nucleoside analogue-naive subjects):

- Age greater than 18 years and older, male or female.

- Known serum HBsAg positivity for 24 weeks.

- Detectable HBV DNA greater than 10(5) copies per ml.

- Serum ALT or AST levels 1.5 times the upper limit of normal (for ALT: greater than or
equal to 62 U/L and for AST greater than or equal to 46 U/L) based on at least two
determinations taken at least one month apart during the 24 weeks before study entry.

- Liver biopsy within 2 years of entry that is consistent with chronic.

- Written informed consent.

INCLUSION CRITERIA SALVAGE STUDY (nucleoside analogue experienced subjects):

- Age > 18 years and older, male or female

- Known serum HBsAg positivity for 6 months

- Detectable HBV DNA > 10(2) copies/ml.

- Liver biopsy within 5 years of entry that is consistent with chronic hepatitis

- Written informed consent

INCLUSION CRITERIA: SALVAGE STUDY (relapsers)

- Age greater than 18 years and older, male or female.

- Known serum HBsAg positivity for 6 months.

- Detectable HBV DNA greater than 10(3) copies per milliliter.

- Liver biopsy within 5 years of entry that is consistent with chronic hepatitis.

- Written informed consent.

Serum ALT or AST levels 1.5 times the ULN (for ALT: greater than 62 U/L and for AST:
greater than 46 U/L) based on at least two determinations taken at least 2 weeks apart.

EXCLUSION CRITERIA:

- Previous or current treatment with tenofovir or emtricitabine.

- Co-infection with HDV as defined by the presence of anti-HDV in serum and/or HDV
antigen in the liver.

- Co-infection with HCV as defined by the presence of HCV RNA in serum.

- Co-infection with HIV as defined by the presence of anti-HIV in serum.

- Decompensated liver disease as defined by serum bilirubin greater than 2.5 milligram
per deciliter (with direct bilirubin greater than 0.5 milligram per deciliter),
prothrombin time of greater than 2 seconds prolonged, a serum albumin of less than 3
grams per deciliter, or a history of ascites, variceal bleeding or hepatic
encephalopathy.

- Presence of other causes of liver disease (i.e. hemochromatosis, Wilson disease,
alcoholic liver disease, nonalcoholic steatohepatitis, alpha-1anti-trypsin
deficiency).

- A history of organ transplantation or in the absence of organ transplantation, any
immunosuppressive therapy requiring the use of more than 5 milligrams of prednisone
(or its equivalent) daily.

- Significant systemic illness other than liver diseases including congestive heart
failure, renal failure, chronic pancreatitis, diabetes mellitus with poor control
that in the opinion of the investigator may interfere with therapy.

- Pregnancy or inability to practice contraception in patients capable of bearing or
fathering children and lactating women.

- Hepatocellular carcinoma (HCC), or the presence of a mass on imaging studies of the
liver that is suggest of HCc, or an alpha-fetoprotein level of greater than 500ng/mL.

- 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.

- Sensory or motor neuropathy apparent from medical history and physical examination.

- Creatinine clearance less than 50 ml/min, serum creatinine greater than 1.3 mg/dl or
urine protein greater than 1 gram/24 hours; creatinine clearance will be determined
on the average of two 24 hour urine specimens. Accuracy of collection will be ensured
by documenting appropriate total creatinine excretion in the 24 hour urine specimen
(15mg/kg) and correcting for the patient's age, gender and body surface area.

- Concurrent use of nephrotoxic agents (e.g. aminoglycosides, amphotericin B,
vancomycin, foscarnet, cis-platinum, 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.

- History of hypersensitivity to nucleoside analogues.

- Active ethanol/drug abuse/psychiatric problems such as major depression,
schizophrenia, bipolar illness, obsessive-compulsive disorder, severe anxiety,
personality disorder that, in the investigator's opinion, might interfere with
participation in the study.

- History of renal tubular acidosis.

- History of malignancy or treatment for a malignancy within the past 5 years.

- Presence of conditions that, in the opinion of the investigators, would not allow the
patient to be followed in the current study for at least 5 years.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Chronic Hepatitis B e Antigen Negative

Chronic Hepatitis B e Antigen Positive

Intervention(s)

Drug: Tenofovir/ & Emtricitabine

Primary Outcome(s)

Maintained suppression of HBV DNA below 102 copies/ml (< 95 IU/ml, undetectable by current PCR-based assays, Roche Amplicor assay). [Time Frame: No]

Secondary Outcome(s)

Normalization of ALT levels and histological improvements which are expected to occur in all patients with full suppression of HBV DNA and in a proportion of those with partial suppression. Other endpoints will be loss of HBeAg and loss of HBsA... [Time Frame: No]

Secondary ID(s)

07-DK-0207

070207

Source(s) of Monetary Support

Please refer to primary and secondary sponsors