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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00507507
Other study ID # GS-US-203-0101
Secondary ID
Status Completed
Phase Phase 2
First received July 25, 2007
Last updated July 7, 2015
Start date September 2007
Est. completion date August 2012

Study information

Verified date July 2015
Source Gilead Sciences
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

The main objective of the study was to evaluate the antiviral activity of tenofovir disoproxil fumarate (tenofovir DF) monotherapy versus emtricitabine (FTC) plus tenofovir DF combination therapy for the treatment of chronic hepatitis B (HBV) in participants in the immune tolerant phase of HBV infection.

The efficacy of tenofovir DF monotherapy versus FTC plus tenofovir DF combination therapy was evaluated for suppression of the virus (decrease in HBV DNA), serological response (generation of antibodies to the virus), biochemical response (changes in liver enzymes), and the development of drug-resistant mutations. The safety and tolerability of both tenofovir DF monotherapy and FTC plus tenofovir DF were evaluated by routine monitoring for adverse events and changes in laboratory parameters.

Participants were randomized in a 1:1 ratio to receive tenofovir DF monotherapy or FTC plus tenofovir DF. All subjects were to continue on blinded study medication until the last subject reached Week 192. Participants who permanently discontinued study drug (on or before Week 192) were followed for a 24-week treatment-free follow-up period, or until initiation of alternative HBV therapy, whichever occurred first. Subjects who discontinued study drug on or after Week 48 because of hepatitis B surface antigen (HBsAg) loss or seroconversion to antibody to hepatitis B surface antigen (anti-HBs), however, were to have returned for their regularly scheduled through Week 192 and every 16 weeks thereafter until the last subject reached Week 192.


Recruitment information / eligibility

Status Completed
Enrollment 126
Est. completion date August 2012
Est. primary completion date February 2012
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 69 Years
Eligibility Inclusion Criteria:

- Chronic HBV infection, defined as positive serum HBsAg for at least 6 months or HBsAg positive > 3 months and positive for immunoglobulin G antibody against hepatitis B core antigen

- 18 through 69 years of age, inclusive

- Hepatitis B e antigen (HBeAg) positive

- HBV DNA = 10^8 copies/mL

- ALT = the upper limit of the normal range (ULN)

- Willing and able to provide written informed consent

- Negative serum beta-human chorionic gonadotropin (for females of childbearing potential only)

- Calculated creatinine clearance = 70 mL/min

- Hemoglobin = 10 g/dL

- Neutrophils = 1,500/mm^3

- No prior oral HBV therapy (eg, nucleotide and/or nucleoside therapy or other investigational agents for HBV infection)

Exclusion Criteria:

- Pregnant women, women who were breast feeding, or who believed they may have wished to become pregnant during the course of the study

- Males and females of reproductive potential unwilling to use an effective method of contraception during the study

- Decompensated liver disease defined as direct (conjugated) bilirubin > 1.2 x ULN, prothrombin time > 1.2 x ULN, platelets < 150,000/mm^3, serum albumin < 3.5 g/dL, or prior history of clinical hepatic decompensation (eg, ascites, jaundice, encephalopathy, or variceal hemorrhage)

- Received interferon (pegylated or not) therapy within 6 months of the screening visit

- Alpha-fetoprotein > 50 ng/mL

- Evidence of hepatocellular carcinoma

- Coinfection with hepatitis C virus (by serology), HIV, or hepatitis D virus

- Significant renal, cardiovascular, pulmonary, or neurological disease

- Received solid organ or bone marrow transplantation

- Was currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion

- Had proximal tubulopathy

- Known hypersensitivity to the study drugs, the metabolites, or formulation excipients

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Intervention

Drug:
Tenofovir DF
Tenofovir disoproxil fumarate (tenofovir DF) 300 mg tablet taken orally once daily
FTC
Emtricitabine (FTC) 200 mg capsule taken orally once daily
Placebo
Placebo to match FTC taken once daily

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Hong Kong,  New Zealand,  Poland,  Singapore,  Taiwan,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Participants With HBV DNA < 400 Copies/mL at Week 192 The percentage of participants with HBV DNA < 400 copies/mL at Week 192 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation. Week 192 No
Secondary Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144 The percentage of participants with HBV DNA < 400 copies/mL at Weeks 48, 96, and 144 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation. Weeks 48, 96, and 144 No
Secondary Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192 The percentage of participants with HBV DNA < 169 copies/mL at Weeks 48, 96, 144, and 192 was analyzed. Participants with missing data were considered to have failed to achieve the criteria for evaluation. Weeks 48, 96, 144, and 192 No
Secondary Change From Baseline in HBV DNA at Week 48 The change from baseline in HBV DNA at Week 48 was analyzed. Baseline to Week 48 No
Secondary Change From Baseline in HBV DNA at Week 96 The change from baseline in HBV DNA at Week 96 was analyzed. Baseline to Week 96 No
Secondary Change From Baseline in HBV DNA at Week 144 The change from baseline in HBV DNA at Week 144 was analyzed. Baseline to Week 144 No
Secondary Change From Baseline in HBV DNA at Week 192 The change from baseline in HBV DNA at Week 192 was analyzed. Baseline to Week 192 No
Secondary Number of Participants With Normal Alanine Aminotransferase (ALT) at Weeks 48, 96, 144, and 192 Range of normal ALT was 6 to 34 U/L for females, 6 to 43 U/L for males. Participants with missing data were considered to have failed to achieve the criteria for evaluation. Weeks 48, 96, 144, and 192 No
Secondary Number of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 48, 96, 144, and 192 The number of participants with HBeAg loss at Weeks 48, 96, 144, and 192 was analyzed. Loss of HBeAg was defined as change of detectable HBeAg from positive to negative.
No statistical analysis is presented for Week 48 because no participants met the criteria at that time point.
Weeks 48, 96, 144, and 192 No
Secondary Number of Participants With Seroconversion to Antibody Against HBeAg (Anti-HBe) at Weeks 48, 96, 144, and 192 The number of participants with seroconversion to anti-HBe at Weeks 48, 96, 144, and 192 was analyzed. Seroconversion to anti-HBe was defined as change of detectable antibody to HBeAg from negative to positive.
No statistical analysis is presented for Week 48 because no participants met the criteria at that time point.
Weeks 48, 96, 144, and 192 No
Secondary Number of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 48, 96, 144, and 192 The number of participants with HBsAg loss at Weeks 48, 96, 144, and 192 was analyzed. Loss of HBsAg was defined as change of detectable HBsAg from positive to negative. Weeks 48, 96, 144, and 192 No
Secondary Number of Participants With Seroconversion to Antibody to HBsAg (Anti-HBs) at Weeks 48, 96, 144, and 192 The number of participants with seroconversion to anti-HBs at Weeks 48, 96, 144, and 192 was analyzed. Seroconversion to anti-HBs was defined as change of detectable antibody to HBsAg from negative to positive. Weeks 48, 96, 144, and 192 No
Secondary Occurrence of HBV Resistance Mutations The development of HBV resistance mutations (occurrence of conserved site changes and/or polymorphic site changes) was analyzed for the overall study period (through Week 192). Baseline to Week 192 No
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