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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 août 2020 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Type d'étude

Interventionnel

Inscription (Réel)

490

Phase

  • Phase 3

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Canada
      • Edmonton, Canada
      • Toronto, Canada
      • Vancouver, Canada
  • Corée, République de
      • Daegu, Corée, République de, 700-721
      • Seoul, Corée, République de
      • Seoul, Corée, République de, 135-710
      • Seoul, Corée, République de, 05505
      • Seoul, Corée, République de, 03722
      • Seoul, Corée, République de, 152-703
      • Seoul, Corée, République de, 06973
      • Seoul, Corée, République de, 03830
    • Gyeonggi-d
      • Goyang, Gyeonggi-d, Corée, République de
  • Espagne
      • Barcelona, Espagne
      • Majadahonda, Espagne
  • Hong Kong
      • Hong Kong, Hong Kong
      • Kowloon, Hong Kong
  • Italie
      • Milan, Italie, 20122
  • Royaume-Uni
      • London, Royaume-Uni
      • London, Royaume-Uni, E1 1BB
  • Taïwan
      • Chiayi City, Taïwan, 60002
      • Kaohsiung, Taïwan
      • Taipei City, Taïwan, 10002
  • États-Unis
    • California
      • Los Angeles, California, États-Unis
      • Palo Alto, California, États-Unis
      • Pasadena, California, États-Unis
      • San Diego, California, États-Unis
      • San Francisco, California, États-Unis
      • San Jose, California, États-Unis
    • Maryland
      • Baltimore, Maryland, États-Unis
    • Massachusetts
      • Boston, Massachusetts, États-Unis
    • Michigan
      • Novi, Michigan, États-Unis
    • New York
      • Flushing, New York, États-Unis
      • Flushing, New York, États-Unis, 11355
      • New York, New York, États-Unis
      • New York, New York, États-Unis, 10029
    • Pennsylvania
      • Philadelphia, Pennsylvania, États-Unis
      • Philadelphia, Pennsylvania, États-Unis, 19107
    • Tennessee
      • Nashville, Tennessee, États-Unis
    • Texas
      • Sugar Land, Texas, États-Unis, 77478

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Double

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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.
Médicament: TAF
Comprimé de 25 mg administré par voie orale une fois par jour
Autres noms:
  • Vemlidy®
  • GS-7340
Médicament: TDF Placebo
Comprimé administré par voie orale une fois par jour
Comparateur actif: 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.
Médicament: TAF
Comprimé de 25 mg administré par voie orale une fois par jour
Autres noms:
  • Vemlidy®
  • GS-7340
Médicament: TDF
Comprimé de 300 mg administré par voie orale une fois par jour
Autres noms:
  • Viread®
Médicament: TAF Placebo
Comprimé administré par voie orale une fois par jour

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
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
Délai: 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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Percentage of Participants With HBV DNA Levels ≥ 20 IU/mL at Week 96, as Determined by the Modified US FDA-Defined Snapshot Algorithm
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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)
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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
Délai: 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

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Gilead Sciences

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Publications générales

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

29 décembre 2016

Achèvement primaire (Réel)

10 septembre 2018

Achèvement de l'étude (Réel)

30 janvier 2020

Dates d'inscription aux études

Première soumission

29 novembre 2016

Première soumission répondant aux critères de contrôle qualité

29 novembre 2016

Première publication (Estimation)

1 décembre 2016

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

14 septembre 2020

Dernière mise à jour soumise répondant aux critères de contrôle qualité

24 août 2020

Dernière vérification

1 août 2020

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

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

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

OUI

Description du régime IPD

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

Délai de partage IPD

18 months after study completion

Critères d'accès au partage IPD

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

Type d'informations de prise en charge du partage d'IPD

  • PROTOCOLE D'ÉTUDE
  • SÈVE

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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Essais cliniques sur TAF

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Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

CROs by country

CROs in Malaysia

Conditions

Maladies rares

Interventions en matière de drogue

Compléments alimentaires

Commanditaire / collaborateurs

Emplacements

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