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

24. august 2020 opdateret af: Gilead Sciences

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

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.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

490

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Canada
      • Edmonton, Canada
      • Toronto, Canada
      • Vancouver, Canada
  • Det Forenede Kongerige
      • London, Det Forenede Kongerige
      • London, Det Forenede Kongerige, E1 1BB
  • Forenede Stater
    • California
      • Los Angeles, California, Forenede Stater
      • Palo Alto, California, Forenede Stater
      • Pasadena, California, Forenede Stater
      • San Diego, California, Forenede Stater
      • San Francisco, California, Forenede Stater
      • San Jose, California, Forenede Stater
    • Maryland
      • Baltimore, Maryland, Forenede Stater
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater
    • Michigan
      • Novi, Michigan, Forenede Stater
    • New York
      • Flushing, New York, Forenede Stater
      • Flushing, New York, Forenede Stater, 11355
      • New York, New York, Forenede Stater
      • New York, New York, Forenede Stater, 10029
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forenede Stater
      • Philadelphia, Pennsylvania, Forenede Stater, 19107
    • Tennessee
      • Nashville, Tennessee, Forenede Stater
    • Texas
      • Sugar Land, Texas, Forenede Stater, 77478
  • Hong Kong
      • Hong Kong, Hong Kong
      • Kowloon, Hong Kong
  • Italien
      • Milan, Italien, 20122
  • Korea, Republikken
      • Daegu, Korea, Republikken, 700-721
      • Seoul, Korea, Republikken
      • Seoul, Korea, Republikken, 135-710
      • Seoul, Korea, Republikken, 05505
      • Seoul, Korea, Republikken, 03722
      • Seoul, Korea, Republikken, 152-703
      • Seoul, Korea, Republikken, 06973
      • Seoul, Korea, Republikken, 03830
    • Gyeonggi-d
      • Goyang, Gyeonggi-d, Korea, Republikken
  • Spanien
      • Barcelona, Spanien
      • Majadahonda, Spanien
  • Taiwan
      • Chiayi City, Taiwan, 60002
      • Kaohsiung, Taiwan
      • Taipei City, Taiwan, 10002

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

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.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Dobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: 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.
Medicin: TAF
25 mg tablet indgivet oralt én gang dagligt
Andre navne:
  • Vemlidy®
  • GS-7340
Medicin: TDF Placebo
Tablet indgivet oralt én gang dagligt
Aktiv komparator: 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.
Medicin: TAF
25 mg tablet indgivet oralt én gang dagligt
Andre navne:
  • Vemlidy®
  • GS-7340
Medicin: TDF
300 mg tablet indgivet oralt én gang dagligt
Andre navne:
  • Viread®
Medicin: TAF Placebo
Tablet indgivet oralt én gang dagligt

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
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
Tidsramme: Week 48

The percentage of participants with HBV DNA ≥ 20 IU/mL at Week 48 was analyzed using the modified US FDA-defined snapshot algorithm, which included participants who:

  1. Had the last available on-treatment HBV DNA ≥ 20 IU/mL in the Week 48 analysis window (from Day 295 to Day 378, inclusive), or

  2. Did not have on-treatment HBV DNA data available in the Week 48 analysis window and

    • Discontinued study drug prior to or in the Week 48 analysis window due to lack of efficacy, or
    • Discontinued study drug prior to or in the Week 48 analysis window due to reason other than lack of efficacy and had the last available on-treatment HBV DNA ≥ 20 IU/mL
Week 48

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Percentage of Participants With HBV DNA Levels ≥ 20 IU/mL at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm
Tidsramme: Week 96

The percentage of participants with HBV DNA ≥ 20 IU/mL at Week 96 was analyzed using the modified US FDA-defined snapshot algorithm, which included participants who:

  1. Had the last available on-treatment HBV DNA ≥ 20 IU/mL in the Week 96 analysis window (from Day 589 to Day 840, inclusive), or

  2. Did not have on-treatment HBV DNA data available in the Week 96 analysis window and

    • Discontinued study drug prior to or in the Week 96 analysis window due to lack of efficacy, or
    • Discontinued study drug prior to or in the Week 96 analysis window due to reason other than lack of efficacy and had the last available on-treatment HBV DNA ≥ 20 IU/mL
Week 96
Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 48
Tidsramme: Weeks 48
The percentage of participants with HBV DNA < 20 IU/mL at Week 48 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 48 analysis window. Missing=Failure (M = F) approach was used for analysis.
Weeks 48
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 48
Tidsramme: Week 48
The percentage of participants with HBV DNA < 20 IU/mL at Week 48 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 48 analysis window. The method of determining percentage of participants with HBV DNA levels <20 IU/mL (target detected/not detected i.e., lower limit of detection) at Week 48, was handled by M = F, and Missing=Excluded (M = E) approaches.
Week 48
Percentage of Participants With HBV DNA Levels < 20 IU/mL at Week 96
Tidsramme: Week 96
The percentage of participants with HBV DNA < 20 IU/mL at Week 96 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 96 analysis window. M = F approach was used for analysis.
Week 96
Percentage of Participants With HBV DNA Levels < 20 IU/mL (Target Detected/Not Detected) at Week 96
Tidsramme: Week 96
The percentage of participants with HBV DNA < 20 IU/mL at Week 96 was analyzed, which included participants who have the last available on-treatment HBV DNA, 20 IU/mL in the Week 96 analysis window. The method of determining percentage of participants with HBV DNA levels <20 IU/mL (target detected/not detected i.e., lower limit of detection) at Week 96, was handled by Missing=Failure (M = F), and Missing=Excluded (M = E) approaches.
Week 96
Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Week 48
Tidsramme: Week 48
HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline visit with baseline HBeAb negative or missing. The M = F approach was used for this analysis.
Week 48
Percentage of Participants With HBeAg Seroconversion at Week 48
Tidsramme: Week 48
HBeAg seroconversion was defined as HBeAg loss and HBeAb changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Week 48
Percentage of Participants With HBeAg Loss at Week 96
Tidsramme: Week 96
HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline visit with baseline HBeAb negative or missing. The M = F approach was used for this analysis.
Week 96
Percentage of Participants With HBeAg Seroconversion at Week 96
Tidsramme: Week 96
HBeAg seroconversion was defined as HBeAg loss and HBeAb changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Week 96
Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 48
Tidsramme: Week 48
HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline visit with baseline HBsAb negative or missing. The M = F approach was used for this analysis.
Week 48
Percentage of Participants With HBsAg Seroconversion at Week 48
Tidsramme: Week 48
HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Week 48
Percentage of Participants With HBsAg Loss at Week 96
Tidsramme: Week 96
HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline visit with baseline HBsAb negative or missing. The M = F approach was used for this analysis.
Week 96
Percentage of Participants With HBsAg Seroconversion at Week 96
Tidsramme: Week 96
HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Week 96
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)
Tidsramme: Week 48
Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to < 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to < 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis.
Week 48
Percentage of Participants With Normalized ALT at Week 48 (by Central Laboratory and AASLD Criteria)
Tidsramme: Week 48
ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to < 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to < 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis.
Week 48
Percentage of Participants With Normal ALT at Week 96 (by Central Laboratory and the AASLD Criteria)
Tidsramme: Week 96
Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to < 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to < 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis.
Week 96
Percentage of Participants With Normalized ALT at Week 96 (by Central Laboratory and AASLD Criteria)
Tidsramme: Week 96
ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to < 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to < 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. M = F approach was used for analysis.
Week 96
Change From Baseline in FibroTest® Score at Week 48
Tidsramme: Baseline; Week 48
The FibroTest score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 48 minus the value at Baseline.
Baseline; Week 48
Change From Baseline in FibroTest® Score at Week 96
Tidsramme: Baseline; Week 96
The FibroTest score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 96 minus the value at Baseline.
Baseline; Week 96
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Tidsramme: Baseline; Week 48
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Baseline; Week 48
Percent Change From Baseline in Hip BMD at Week 96
Tidsramme: Baseline; Week 96
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Baseline; Week 96
Percent Change From Baseline in Spine BMD at Week 48
Tidsramme: Baseline; Week 48
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Baseline; Week 48
Percent Change From Baseline in Spine BMD at Week 96
Tidsramme: Baseline; Week 96
Percent Change = Change from baseline at a postbaseline visit/baseline * 100%.
Baseline; Week 96
Change From Baseline in Estimated Glomerular Filtration Rate Calculated Using the Cockcroft-Gault Equation (eGFR-CG) at Week 48
Tidsramme: Baseline; Week 48

Cockcroft-Gault formula is as follows:

  • For men: Glomerular filtration rate (GFR) = (140 - age in years) * body weight in kg / 72 * serum creatinine (mg/dL)
  • For women: GFR = 0.85 * (140 - age in years) * body weight in kg / 72 * serum creatinine (mg/dL).

Change from baseline was calculated as the value at Week 48 minus the value at Baseline.
Baseline; Week 48
Change From Baseline in eGFR-CG at Week 96
Tidsramme: Baseline; Week 96

Cockcroft-Gault formula is as follows:

  • For men: Glomerular filtration rate (GFR) = (140 - age in years) * body weight in kg / 72 * serum creatinine (mg/dL)
  • For women: GFR = 0.85 * (140 - age in years) * body weight in kg / 72 * serum creatinine (mg/dL).

Change from baseline was calculated as the value at Week 96 minus the value at Baseline.
Baseline; Week 96

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Gilead Sciences

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

29. december 2016

Primær færdiggørelse (Faktiske)

10. september 2018

Studieafslutning (Faktiske)

30. januar 2020

Datoer for studieregistrering

Først indsendt

29. november 2016

Først indsendt, der opfyldte QC-kriterier

29. november 2016

Først opslået (Skøn)

1. december 2016

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

14. september 2020

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

24. august 2020

Sidst verificeret

1. august 2020

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • GS-US-320-4018
  • 2016-003632-20 (EudraCT nummer)

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

JA

IPD-planbeskrivelse

Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy

IPD-delingstidsramme

18 months after study completion

IPD-delingsadgangskriterier

A secured external environment with username, password, and RSA code.

IPD-deling Understøttende informationstype

  • STUDY_PROTOCOL
  • SAP

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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