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)

NCT00507507 | Completed Phase 2 Results DMC

• 1 other identifier: GS-US-203-0101
• Study Type: interventional
• Target: 126
• Locations: 11 countries
• Sites: 45

Brief 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.

Conditions

Chronic Hepatitis B

Keywords

tenofovir; monotherapy; emtricitabine; combination; hepatitis B

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (12)

• Percentage of Participants With HBV DNA < 400 Copies/mL at Weeks 48, 96, and 144

  Weeks 48, 96, and 144

• Percentage of Participants With HBV DNA < 169 Copies/mL at Weeks 48, 96, 144, and 192

  Weeks 48, 96, 144, and 192

• Change From Baseline in HBV DNA at Week 48

  Baseline to Week 48

• Change From Baseline in HBV DNA at Week 96

  Baseline to Week 96

• Change From Baseline in HBV DNA at Week 144

  Baseline to Week 144

Study Arms (2)

Tenofovir DF

EXPERIMENTAL

Participants were randomized to receive tenofovir DF plus placebo to match FTC once daily.

Drug: Tenofovir DF; Drug: Placebo

FTC+Tenofovir DF

EXPERIMENTAL

Participants were randomized to receive FTC plus tenofovir DF once daily.

Drug: Tenofovir DF; Drug: FTC

Interventions

Tenofovir DF DRUG

Tenofovir disoproxil fumarate (tenofovir DF) 300 mg tablet taken orally once daily

Also known as: Viread®

FTC+Tenofovir DF; Tenofovir DF

FTC DRUG

Emtricitabine (FTC) 200 mg capsule taken orally once daily

Also known as: Emtriva®

FTC+Tenofovir DF

Placebo DRUG

Placebo to match FTC taken once daily

Tenofovir DF

Eligibility Criteria

• Age: 18 Years - 69 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (45)

Unknown Facility

Los Angeles, California, 90048, United States

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San Diego, California, 92115, United States

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San Francisco, California, 11355, United States

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Miami, Florida, 33136, United States

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Detroit, Michigan, 48202, United States

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Manhasset, New York, 11030, United States

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New York, New York, 10021, United States

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New York, New York, 10029-6574, United States

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Germantown, Tennessee, 38138, United States

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Seattle, Washington, 98111, United States

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Camperdown, New South Wales, 2050, Australia

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Westmead, New South Wales, 2145, Australia

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Heidelburg, Victoria, 3081, Australia

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Melbourne, Victoria, 3004, Australia

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Calgary, Alberta, T2N4N1, Canada

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Vancouver, British Columbia, V5Z1H2, Canada

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Toronto, Ontario, M5G 2C4, Canada

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Lille, 59037, France

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Lyon, 69288, France

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Strasbourg, 67091, France

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Berlin, 10969, Germany

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Berlin, 13353, Germany

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Düsseldorf, 40237, Germany

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Frankfurt, 60590, Germany

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Hamburg, 20251, Germany

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Hanover, 30623, Germany

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Heidelberg, 69120, Germany

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Herne, 44623, Germany

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Mainz, 55131, Germany

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Pokfulam, Hong Kong

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Shatin, Hong Kong

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Tai Po, Hong Kong

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Grafton, Auckland, 1150, New Zealand

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Hamilton, New Zealand

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Bydgoszcz, 85-030, Poland

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Chorzów, 41-500, Poland

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Warsaw, 01-201, Poland

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Singapore, 119074, Singapore

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Singapore, 529889, Singapore

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Kaohsiung City, 807, Taiwan

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Kaoshiung, 833, Taiwan

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Tainan, 107, Taiwan

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Taipei, Taiwan

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London, NW3 2QG, United Kingdom

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Sheffield, S10 2JF, United Kingdom

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MeSH Terms

Conditions

Hepatitis B, Chronic; Hepatitis B

Interventions

Tenofovir; Emtricitabine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.

ClinicalTrialDisclosures@gilead.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2007
• First Posted: July 26, 2007
• Study Start: September 1, 2007
• Primary Completion: February 1, 2012
• Study Completion: August 1, 2012
• Last Updated: July 17, 2015
• Results First Posted: August 8, 2013

Record last verified: 2015-07

Locations

PL (3); SG (2); DE (9); FR (3); AU (4); NZ (2); HK (3); TW (4); GB (2); CA (3); US (10)