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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 augusti 2020 uppdaterad av: 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.

Studieöversikt

Status

Avslutad

Betingelser

Intervention / Behandling

Studietyp

Interventionell

Inskrivning (Faktisk)

490

Fas

  • Fas 3

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Dubbel

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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.
Läkemedel: TAF
25 mg tablett administreras oralt en gång dagligen
Andra namn:
  • Vemlidy®
  • GS-7340
Läkemedel: TDF Placebo
Tablett administreras oralt en gång dagligen
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.
Läkemedel: TAF
25 mg tablett administreras oralt en gång dagligen
Andra namn:
  • Vemlidy®
  • GS-7340
Läkemedel: TDF
300 mg tablett administreras oralt en gång dagligen
Andra namn:
  • Viread®
Läkemedel: TAF Placebo
Tablett administreras oralt en gång dagligen

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
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
Tidsram: 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

Sekundära resultatmått

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

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Gilead Sciences

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Allmänna publikationer

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

29 december 2016

Primärt slutförande (Faktisk)

10 september 2018

Avslutad studie (Faktisk)

30 januari 2020

Studieregistreringsdatum

Först inskickad

29 november 2016

Först inskickad som uppfyllde QC-kriterierna

29 november 2016

Första postat (Uppskatta)

1 december 2016

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

14 september 2020

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

24 augusti 2020

Senast verifierad

1 augusti 2020

Mer information

Termer relaterade till denna studie

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

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

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

JA

IPD-planbeskrivning

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

Tidsram för IPD-delning

18 months after study completion

Kriterier för IPD Sharing Access

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

IPD-delning som stöder informationstyp

  • STUDY_PROTOCOL
  • SAV

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Ja

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

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