Study to Evaluate Efficacy and Safety of Switching From TDF to TAF in Adults With Chronic Hepatitis B Who Are Virologically Suppressed

Gilead Sciences

Status and phase: Completed; Phase 3

Conditions: Chronic Hepatitis B

Treatments: Drug: TDF; Drug: TDF Placebo; Drug: TAF; Drug: TAF Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02979613

GS-US-320-4018

2016-003632-20 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 490 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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490 participants in 2 patient groups

TAF 25 mg

Experimental group

Description:

Double-blind (DB) phase: TAF 25 mg + TDF placebo for up to 53 weeks. Open-label extension (OLE) phase: TAF 25 mg for up to 52 weeks.

Treatment:

Drug: TAF

Drug: TDF Placebo

TDF 300 mg

Active Comparator group

Description:

DB phase: TDF 300 mg + TAF placebo for up to 50 weeks. OLE phase: TAF 25 mg for up to 52 weeks.

Treatment:

Drug: TAF

Drug: TAF Placebo

Drug: TDF