Clinical trial NCT02979613: Study to Evaluate Efficacy and Safety of Switching From TDF to TAF in Adults With Chronic Hepatitis B Who Are Virologically Suppressed
Official title: A Phase 3, Randomized, Double-Blind Study to Evaluate the Efficacy and Safety of Switching From Tenofovir Disoproxil Fumarate (TDF) 300 mg QD to Tenofovir Alafenamide (TAF) 25 mg QD in Subjects With Chronic Hepatitis B Who Are Virologically Suppressed
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Hepatitis B
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-12-01
Enrollment: 490
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of switching to tenofovir alafenamide (TAF) versus continuing tenofovir disoproxil fumarate (TDF) in virologically suppressed adults with chronic hepatitis B virus (HBV) infection.


Eligibility criteria: Key Inclusion Criteria:

* Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
* Adult male and non-pregnant, non-lactating females
* Documented evidence of chronic hepatitis B virus (HBV) infection previously
* Maintained on tenofovir disoproxil fumarate (TDF) 300 mg once daily for at least 48 weeks, and as monotherapy for chronic hepatitis B for at least 24 weeks with viral suppression (HBV DNA \< lower limit of quantitation) for a minimum of 12 weeks prior to screening
* Adequate renal function
* Normal Electrocardiogram

Key Exclusion Criteria:

* Pregnant women or women 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 (HCV), hepatitis D virus (HDV), or human immunodeficiency virus (HIV)
* Evidence of hepatocellular carcinoma
* Current evidence of, or recent (≤ 5 year) history of clinical hepatic decompensation
* Abnormal hematological and biochemical parameters, including:

  * Hemoglobin \< 10 g/dL
  * Absolute neutrophil count \< 750/mm\^3
  * Platelets ≤ 50,000/mm\^3
  * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 5 × upper limit of the normal (ULN)
  * Albumin \< 3.0 mg/ dL
  * International normalized ratio (INR) \> 1.5 × ULN (unless stable on anticoagulant regimen)
  * Total bilirubin \> 2.5 × ULN
* Received solid organ or bone marrow transplant
* Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (eg, basal cell skin cancer). Individuals under evaluation for possible malignancy are not eligible.
* Currently receiving therapy with immunomodulators (eg, corticosteroids), nephrotoxic agents, or agents capable of modifying renal excretion
* Individuals receiving ongoing therapy with drugs not to be used with TAF or TDF 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 compliance
* Any other clinical condition or prior therapy that, in the opinion of the investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements.
* Use of investigational agents within 3 months of screening, unless allowed by the sponsor

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants With Hepatitis B Virus (HBV) DNA Levels ≥ 20 IU/mL at Week 48, as Determined by the Modified United States Food and Drug Administration (US FDA)-Defined Snapshot Algorithm
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With HBV DNA Levels ≥ 20 IU/mL at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm
timeFrame: Week 96
measure: Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 48
timeFrame: Weeks 48
measure: Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 96
timeFrame: Week 96
measure: Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96
timeFrame: Week 96
measure: Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HBeAg Seroconversion at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HBeAg Loss at Week 96
timeFrame: Week 96
measure: Percentage of Participants With HBeAg Seroconversion at Week 96
timeFrame: Week 96
measure: Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HBsAg Seroconversion at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HBsAg Loss at Week 96
timeFrame: Week 96
measure: Percentage of Participants With HBsAg Seroconversion at Week 96
timeFrame: Week 96
measure: Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 48 (by Central Laboratory and the American Association for the Study of Liver Diseases [AASLD] Criteria)
timeFrame: Week 48
measure: Percentage of Participants With Normalized ALT at Week 48 (by Central Laboratory and AASLD Criteria)
timeFrame: Week 48
measure: Percentage of Participants With Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria)
timeFrame: Week 96
measure: Percentage of Participants With Normalized ALT at Week 96 (by Central Laboratory and AASLD Criteria)
timeFrame: Week 96
measure: Change From Baseline in FibroTest® Score at Week 48
timeFrame: Baseline; Week 48
measure: Change From Baseline in FibroTest® Score at Week 96
timeFrame: Baseline; Week 96
measure: Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
timeFrame: Baseline; Week 48
measure: Percent Change From Baseline in Hip BMD at Week 96
timeFrame: Baseline; Week 96
measure: Percent Change From Baseline in Spine BMD at Week 48
timeFrame: Baseline; Week 48
measure: Percent Change From Baseline in Spine BMD at Week 96
timeFrame: Baseline; Week 96
measure: Change From Baseline in Estimated Glomerular Filtration Rate Calculated Using the Cockcroft-Gault Equation (eGFR-CG) at Week 48
timeFrame: Baseline; Week 48
measure: Change From Baseline in eGFR-CG at Week 96
timeFrame: Baseline; Week 96
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: Pasadena
country: United States
state: California
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: San Jose
country: United States
state: California
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Novi
country: United States
state: Michigan
city: Flushing
country: United States
state: New York
city: Flushing
country: United States
state: New York
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Philadelphia
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Nashville
country: United States
state: Tennessee
city: Sugar Land
country: United States
state: Texas
city: Edmonton
country: Canada
city: Toronto
country: Canada
city: Vancouver
country: Canada
city: Hong Kong
country: Hong Kong
city: Kowloon
country: Hong Kong
city: Milan
country: Italy
city: Goyang
country: Korea, Republic of
state: Gyeonggi-d
city: Daegu
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Barcelona
country: Spain
city: Majadahonda
country: Spain
city: Chiayi City
country: Taiwan
city: Kaohsiung
country: Taiwan
city: Taipei City
country: Taiwan
city: London
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Lampertico P, Buti M, Fung S, Ahn SH, Chuang WL, Tak WY, Ramji A, Chen CY, Tam E, Bae H, Ma X, Flaherty JF, Gaggar A, Lau A, Liu Y, Wu G, Suri V, Tan SK, Subramanian GM, Trinh H, Yoon SK, Agarwal K, Lim YS, Chan HLY. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patients with chronic hepatitis B: a randomised, double-blind, phase 3, multicentre non-inferiority study. Lancet Gastroenterol Hepatol. 2020 May;5(5):441-453. doi: 10.1016/S2468-1253(19)30421-2. Epub 2020 Feb 20.