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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01940471
First received: August 20, 2013
Last updated: April 25, 2016
Last verified: April 2016
  Purpose
This study will compare the safety and efficacy of tenofovir alafenamide (TAF) versus tenofovir disoproxil fumarate (TDF) in treatment-naive and treatment-experienced adults with chronic hepatitis B virus (HBV) infection.

Condition Intervention Phase
HBV
Chronic HBV Infections
Drug: TAF
Drug: TDF
Drug: TAF Placebo
Drug: TDF Placebo
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 Positive, Chronic Hepatitis B

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • 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:
  • Proportion of participants with hepatitis B e antigen (HBeAg) loss with seroconversion to antibody against HBeAb (anti-HBe) at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Percent change from baseline in hip bone mineral density (BMD) at Week 48 [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: Yes ]
  • Percent change from baseline in spine BMD at Week 48 [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: Yes ]
  • Change from baseline at Week 48 in serum creatinine [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: Yes ]

Enrollment: 1022
Study Start Date: September 2013
Estimated Study Completion Date: November 2023
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TAF
TAF + TDF placebo for 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
Drug: TAF
TAF 25 mg tablet administered orally once daily
Drug: TDF Placebo
TDF placebo tablet administered orally once daily
Active Comparator: TDF
TDF + TAF placebo for 96 weeks (per amendment 1 & 2) or 144 weeks (per amendment 3)
Drug: TDF
TDF 300 mg tablet administered orally once daily
Other Name: Viread®
Drug: TAF Placebo
TAF placebo tablet administered orally once daily
Experimental: Open-label TAF
All participants who complete the double-blind period (96 weeks or 144 weeks) will be eligible to receive open-label TAF until Week 384 of the study.
Drug: TAF
TAF 25 mg tablet administered orally once daily

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
  • Adult males and non-pregnant, non-lactating females
  • Documented evidence of chronic HBV infection
  • HBeAg-positive, chronic hepatitis B with all of the following:

    • HBeAg-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)
  • 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)
  • Previous treatment with interferon (pegylated or non-pegylated) must have ended at least 6 months prior to the baseline visit
  • Adequate renal function
  • Normal ECG

Exclusion Criteria:

  • Females who are breastfeeding
  • Males and females of reproductive potential who are unwilling to use an "effective", protocol specified method(s) of contraception during the study
  • Co-infection with hepatitis C virus, HIV, or hepatitis D virus
  • Evidence of hepatocellular carcinoma
  • Any history of, or current evidence of, clinical hepatic decompensation
  • Abnormal hematological and biochemical parameters, including aspartate aminotransferase (AST) > 10 x ULN
  • Received solid organ or bone marrow transplant
  • History of malignancy within the past 5 years, with the exception of specific cancers that are cured by surgical resection; individuals under evaluation for possible malignancy are not eligible
  • Currently receiving therapy with immunomodulators (eg, corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion
  • Individuals receiving ongoing therapy with drugs not to be used with tenofovir alafenamide or tenofovir disoproxil fumarate or individuals with a known hypersensitivity to study drugs, metabolites, or formulation excipients
  • Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance
  • 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: NCT01940471

  Show 188 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: John Flaherty, PharmD Gilead Sciences
  More Information

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01940471     History of Changes
Other Study ID Numbers: GS-US-320-0110 
Study First Received: August 20, 2013
Last Updated: April 25, 2016
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 B
Liver Diseases
Digestive System Diseases
Hepadnaviridae Infections
DNA Virus Infections
Virus Diseases
Hepatitis, Viral, Human
Tenofovir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 24, 2016