A Study to Compare Tenofovir DF Versus the Combination of Emtricitabine Plus Tenofovir DF for the Treatment of Chronic Hepatitis B in Patients With Normal Alanine Aminotransferase (ALT)

Chronic Hepatitis B Clinical Trial

Official title:

A Randomized, Double-Blind Study Evaluating Tenofovir Disoproxil Fumarate (DF) Monotherapy Versus the Combination of Emtricitabine and Tenofovir DF for the Treatment of Chronic Hepatitis B

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00507507
• Other study ID #: GS-US-203-0101
• 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

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

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