Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate for Treatment of Hepatitis B e Antigen-Negative Hepatitis B

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01940341
First received: August 20, 2013
Last updated: September 25, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to evaluate the safety and efficacy of tenofovir alafenamide (TAF) compared to that of tenofovir disoproxil fumarate (TDF) in treatment naive and experienced adult subjects with chronic hepatitis B virus (HBV) infection, as determined by the achievement of HBV DNA < 29 IU/mL at Week 48.


Condition Intervention Phase
HBV
Chronic HBV Infections
Drug: Tenofovir alafenamide
Drug: Tenofovir DF
Drug: Placebo to match tenofovir alafenamide
Drug: Placebo to match tenofovir DF
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Tenofovir Alafenamide (TAF) 25 mg QD Versus Tenofovir Disoproxil Fumarate (TDF) 300 mg QD for the Treatment of HBeAg-Negative, Chronic Hepatitis B

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • The proportion of participants with hepatitis B virus (HBV) DNA < 29 IU/mL [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The primary efficacy endpoint is determined by the achievement of HBV DNA < 29 IU/mL at Week 48.


Secondary Outcome Measures:
  • Percent change from baseline in hip and spine bone mineral density (BMD) at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]
  • Change from baseline in serum creatinine at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 390
Study Start Date: September 2013
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tenofovir alafenamide
Tenofovir alafenamide plus placebo to match tenofovir DF for 96 weeks, followed by open-label tenofovir alafenamide through Week 144.
Drug: Tenofovir alafenamide
Tenofovir alafenamide 25 mg tablet administered orally once daily
Drug: Placebo to match tenofovir DF
Placebo to match tenofovir DF administered as a tablet orally once daily
Active Comparator: Tenofovir DF
Tenofovir DF plus placebo to match tenofovir alafenamide for 96 weeks, followed by open-label tenofovir alafenamide through Week 144.
Drug: Tenofovir alafenamide
Tenofovir alafenamide 25 mg tablet administered orally once daily
Drug: Tenofovir DF
Tenofovir DF 300 mg tablet administered orally once daily
Other Name: Viread®
Drug: Placebo to match tenofovir alafenamide
Placebo to match tenofovir alafenamide administered as a tablet orally once daily

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
  2. Adult males and non-pregnant, non-lactating females, 18 years of age and older
  3. Documented evidence of chronic HBV (CHB) infection
  4. Hepatitis e antigen (HBeAg)-negative, chronic hepatitis B with all of the following:

    • HBeAg-negative and hepatitis B e antibody (HBeAb) positive at screening
    • Screening HBV DNA ≥ 2 x 10^4 IU/mL
    • Screening serum alanine aminotransferase (ALT) level > 60 U/L (males) or > 38 U/L (females) and ≤ 10 x the upper limit of the normal range (ULN)
  5. Treatment-naive participants (defined as < 12 weeks of oral antiviral treatment with any nucleoside or nucleotide analogue), OR treatment-experienced participants (defined as participants meeting all entry criteria [including HBV DNA and serum ALT criteria] and with ≥ 12 weeks of previous treatment with any nucleoside or nucleotide analogue)
  6. Previous treatment with interferon (pegylated or non pegylated) must have ended at least 6 months prior to the baseline visit.
  7. Adequate renal function
  8. Normal ECG

Exclusion Criteria:

  1. Females who are breastfeeding
  2. Males and females of reproductive potential who are unwilling to use an "effective", protocol-specified method(s) of contraception during the study
  3. Co-infection with hepatitis C, HIV, or hepatitis D
  4. Evidence of hepatocellular carcinoma
  5. Any clinical and/or laboratory evidence of hepatic decompensation
  6. Abnormal hematological and biochemical parameters, including aspartate aminotransferase (AST) > 10 x ULN
  7. Received solid organ or bone marrow transplant
  8. History of malignancy within the past 5 years, with the exception of specific cancers that are cured by surgical resection; participants under evaluation for possible malignancy are not eligible
  9. Currently receiving therapy with immunomodulators (eg, corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion
  10. Subjects receiving ongoing therapy with drugs not to be used with tenofovir alafenamide or tenofovir disoproxil fumarate or subjects with a known hypersensitivity to study drugs, metabolites, or formulation excipients
  11. Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance
  12. Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with dosing requirements
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01940341

  Show 140 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: John Flaherty, PharmD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01940341     History of Changes
Other Study ID Numbers: GS-US-320-0108
Study First Received: August 20, 2013
Last Updated: September 25, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Bulgaria: Bulgarian Drug Agency
Bulgaria: Ethics committee
Canada: Ethics Review Committee
Canada: Health Canada
China: Food and Drug Administration
France: Agence Nationale de Sécurité du Médicament et des produits de santé
France: Committee for the Protection of Personnes
Germany: Federal Institute for Drugs and Medical Devices
Hong Kong: Department of Health
India: Drugs Controller General of India
Italy: The Italian Medicines Agency
Japan: Ministry of Health, Labor and Welfare
New Zealand: Medsafe
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Agency for Medicines and Medical Devices
Russia: Ministry of Health of the Russian Federation
Singapore: Ministry of Health
South Korea: Ministry of Food and Drug Safety
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Taiwan : Food and Drug Administration
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Vietnam: Ministry of Health

Keywords provided by Gilead Sciences:
Hepatitis
Tenofovir
Viread

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Tenofovir
Tenofovir disoproxil
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014