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

NCT ID: NCT02979613

Last Updated: 2020-09-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

490 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-29

Study Completion Date

2020-01-30

Brief Summary

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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.

Detailed Description

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Conditions

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Chronic Hepatitis B

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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TAF 25 mg

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.

Group Type EXPERIMENTAL

TAF

Intervention Type DRUG

25 mg tablet administered orally once daily

TDF Placebo

Intervention Type DRUG

Tablet administered orally once daily

TDF 300 mg

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

Group Type ACTIVE_COMPARATOR

TAF

Intervention Type DRUG

25 mg tablet administered orally once daily

TDF

Intervention Type DRUG

300 mg tablet administered orally once daily

TAF Placebo

Intervention Type DRUG

Tablet administered orally once daily

Interventions

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TAF

25 mg tablet administered orally once daily

Intervention Type DRUG

TDF

300 mg tablet administered orally once daily

Intervention Type DRUG

TAF Placebo

Tablet administered orally once daily

Intervention Type DRUG

TDF Placebo

Tablet administered orally once daily

Intervention Type DRUG

Other Intervention Names

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Vemlidy® GS-7340 Viread®

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Los Angeles, California, United States

Site Status

Palo Alto, California, United States

Site Status

Pasadena, California, United States

Site Status

San Diego, California, United States

Site Status

San Francisco, California, United States

Site Status

San Jose, California, United States

Site Status

Baltimore, Maryland, United States

Site Status

Boston, Massachusetts, United States

Site Status

Novi, Michigan, United States

Site Status

Flushing, New York, United States

Site Status

Flushing, New York, United States

Site Status

New York, New York, United States

Site Status

New York, New York, United States

Site Status

Philadelphia, Pennsylvania, United States

Site Status

Philadelphia, Pennsylvania, United States

Site Status

Nashville, Tennessee, United States

Site Status

Sugar Land, Texas, United States

Site Status

Edmonton, , Canada

Site Status

Toronto, , Canada

Site Status

Vancouver, , Canada

Site Status

Hong Kong, , Hong Kong

Site Status

Kowloon, , Hong Kong

Site Status

Milan, , Italy

Site Status

Goyang, Gyeonggi-d, South Korea

Site Status

Daegu, , South Korea

Site Status

Seoul, , South Korea

Site Status

Seoul, , South Korea

Site Status

Seoul, , South Korea

Site Status

Seoul, , South Korea

Site Status

Seoul, , South Korea

Site Status

Seoul, , South Korea

Site Status

Seoul, , South Korea

Site Status

Barcelona, , Spain

Site Status

Majadahonda, , Spain

Site Status

Chiayi City, , Taiwan

Site Status

Kaohsiung City, , Taiwan

Site Status

Taipei, , Taiwan

Site Status

London, , United Kingdom

Site Status

London, , United Kingdom

Site Status

Countries

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United States Canada Hong Kong Italy South Korea Spain Taiwan United Kingdom

References

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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.

Reference Type RESULT
PMID: 32087795 (View on PubMed)

Provided Documents

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Document Type: Study Protocol: Original

View Document

Document Type: Study Protocol: Amendment 1

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2016-003632-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-320-4018

Identifier Type: -

Identifier Source: org_study_id

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