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- Essai clinique NCT01063036
Efficacy and Safety Study of Entecavir Plus Tenofovir in Patients With Chronic Hepatitis B Who Failed Previous Treatment
25 novembre 2014 mis à jour par: Bristol-Myers Squibb
A Study of the Safety and Efficacy of Entecavir Plus Tenofovir in Adults With Chronic Hepatitis B Virus Infection With Previous Nucleoside/Nucleotide Treatment Failure
The purpose of this study is to show that the combination of entecavir and tenofovir, is effective and well tolerated in chronic hepatitis B patients who have failed previous treatment.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
144
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
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Berlin, Allemagne, 13353
- Local Institution
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Berlin, Allemagne, 10969
- Local Institution
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Hamburg, Allemagne, 20246
- Local Institution
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Hamburg, Allemagne, 20099
- Local Institution
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Hannover, Allemagne, 30625
- Local Institution
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Heindelberg, Allemagne, 69120
- Local Institution
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Munchen, Allemagne, 81675
- Local Institution
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Tubingen, Allemagne, 72076
- Local Institution
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Barcelona, Espagne, 08025
- Local Institution
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Valencia, Espagne, 46014
- Local Institution
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Clichy, France, 92110
- Local Institution
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Lyons Cedex 04, France, 69317
- Local Institution
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Orleans Cedex 2, France, 45067
- Local Institution
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Strasbourg, France, 67000
- Local Institution
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Bagno A Ripoli (Fi), Italie, 50012
- Local Institution
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Bari, Italie, 70124
- Local Institution
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Foggia, Italie, 71100
- Local Institution
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Milano, Italie, 20122
- Local Institution
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Amsterdam, Pays-Bas, 1105 AZ
- Local Institution
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Arnhem, Pays-Bas, 6815 AD
- Local Institution
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Rotterdam, Pays-Bas, 3015 CE
- Local Institution
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Kielce, Pologne, 25-317
- Local Institution
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Krakow, Pologne, 31-531
- Local Institution
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Lodz, Pologne, 91-347
- Local Institution
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Wroclaw, Pologne, 50-349
- Local Institution
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Bucuresti, Roumanie, 021105
- Local Institution
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Burcuresti, Roumanie, 022328
- Local Institution
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Timisoara, Roumanie, 300 002
- Local Institution
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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
Inclusion Criteria:
- Subjects with chronic hepatitis B virus (HBV) infection; either hepatitis B-e antigen(HBeAg)-negative or HBeAg-positive
- Subjects must have a treatment failure to their current nucleoside/ nucleotide treatment regimen
- Prior entecavir and/or tenofovir monotherapy is allowed
- Subjects must have compensated liver function
Exclusion Criteria:
- Women who are pregnant or breastfeeding
- Evidence of decompensated cirrhosis
- Co-infection with HIV, hepatitis C virus (HCV), or hepatitis D virus (HDV)
- Moderate or severe renal impairment
- Recent history of pancreatitis
- Therapy with interferon, thymosin alpha or other immuno-stimulators within 24 weeks of being assigned to study drug into this study
- Prior entecavir/tenofovir combination therapy
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: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: Entecavir + Tenofovir
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Tablets, Oral, 1 mg, once daily, 96 weeks
Autres noms:
Tablets, Oral, 300 mg, once daily, 96 weeks
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Percentage of Participants With a Virologic Response at Week 48 - Treated Population
Délai: Week 48
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Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL.
Percentage was calculated as number of participants with virologic response at Week 48 divided by the number of treated participants.
Treated participants were evaluated using non-completer (NC) = failure (F).
The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay, in a central laboratory.
The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL.
HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
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Week 48
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Percentage of Participants With a Virologic Response at Week 24 and at Week 96 - Treated Population
Délai: Week 24, Week 96
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Virologic response was defined as Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) less than 50 international units per milliliter (IU/mL); approximately 300 copies/mL.
Percentage was calculated as number of participants with virologic response at Week 24, Week 96 divided by the number of treated participants.
Treated participants were evaluated using non-completer (NC) = failure (F).
The HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay.
The results were reported in IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL.
HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
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Week 24, Week 96
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Change From Baseline in Mean log10 HBV DNA at Weeks 12, 24, 48, and 96 - Treated Evaluable Population
Délai: Baseline to Weeks 12, 24, 48, 96
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HBV DNA by polymerase chain reaction (PCR) was measured using the Roche COBAS(REGISTERED) TaqMan - High Pure System (HPS) assay.
The results were reported in log 10 IU/mL, with the limit of quantification (LOQ) = 29 IU/mL and lower limit of detection (LLD) = 6 IU/mL.
HBV DNA measurements were transformed by the log10 scale when analyzed as a continuous variable, using log10(LOQ-1) for values below LOQ.
Baseline was Day 1, prior to study drug administration.
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Baseline to Weeks 12, 24, 48, 96
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Percentage of Participants With HBV DNA Less Than the Lower Limit of Detection (LLD) at Weeks 24, 48, and 96 - Treated Population
Délai: Weeks 24, 48, 96
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HBV DNA less than (<) LLD (6 IU/mL) was defined/measured by the COBAS(REGISTERED) TaqMan HPS assay at Weeks 24, 48, and 96.
Percentage was calculated as number of participants with HBV DNA < LLD at Weeks 24, 48, 96 divided by the number of treated participants.
Treated participants were evaluated using non-completer (NC) = failure (F).
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Weeks 24, 48, 96
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Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg Positive at Baseline
Délai: Baseline to Weeks 24, 48, and 96
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Loss of HBeAg was defined as being HBeAg-negative at Weeks 24, 48, and 96 in those participants who had been HBeAg-positive at baseline.
Method used for HBeAg was DiaSorin - Anti HBe enzyme immunoassay kit - procedure for qualitative determination of antibodies to HBeAg in human serum or plasma samples.
Percentage was calculated as number of participants with HBeAg loss at Weeks 24 and 48 divided by the number of treated participants who were HBeAg-positive at baseline.
Treated participants (HBeAg-positive at baseline) were evaluated using NC = F. Baseline was Day 1, before start of study drug.
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Baseline to Weeks 24, 48, and 96
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Percentage of Participants With HBe Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBeAg-positive at Baseline
Délai: Baseline, Weeks 24, 48, and 96
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HBe seroconversion was defined as being both HBeAg-negative and HBeAb-positive at Weeks 24, 48, and 96 in those participants who had been HBeAg-positive at baseline.
Method used was DiaSorin - Anti HBe enzyme immunoassay kit - procedure for qualitative determination of antibodies to HBeAg in human serum or plasma samples.
Percentage was calculated as number of participants with HBe seroconversion at Weeks 24, 48, and 96 divided by the number of treated participants who were HBeAg-positive at baseline.
Treated participants (HBeAg-positive at baseline) were evaluated using NC = F. Baseline was Day 1, before start of study drug.
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Baseline, Weeks 24, 48, and 96
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Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Weeks 24, 48, 96 - Treated Population Who Were HBsAg-Positive at Baseline
Délai: Baseline, Weeks 24, 48, 96
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Loss of HBsAg was defined as being HBsAg-negative at Weeks 24, 48, 96 in those participants who had been HBsAg-positive at baseline.
The method used: Immunoassay - ADVIA CENTAUR from SIEMENS: in vitro diagnostic immunoassay for the qualitative and quantitative determination of HBsAg in human serum and plasma (potassium ethylene diamine tetraacetic acid, lithium or sodium heparinized).
Percentage calculated as number of participants with a HBsAg loss at Weeks 24, 48, and 96 divided by the number of treated participants who were HBsAg-positive at baseline (participants were not enrolled into the study unless they were positive for HBsAg).
Treated participants (HBsAg-positive at baseline) were evaluated using NC=F.
Baseline was Day 1, before start of study drug.
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Baseline, Weeks 24, 48, 96
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Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Seroconversion at Weeks 24, 48, and 96 - Treated Population Who Were HBsAg-Positive at Baseline
Délai: Baseline, Weeks 24, 48, and 96
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HBsAg seroconversion was defined as being both HBsAg-negative and HBsAb-positive at Weeks 24, 48, and 96 in those participants who had been HBsAg-positive at baseline.
Percentage was calculated as number of participants with HBs seroconversion at Weeks 24 and 48 divided by the number of treated participants who were HBsAg-positive at baseline.
Positive result for HBsAg was one of the inclusion criteria.
Treated participants (HBsAg positive at baseline) were evaluated using NC=F.
The method used was an Immunoassay testing - ADVIA CENTAUR from SIEMENS: in vitro diagnostic immunoassay for the qualitative and quantitative determination of HBsAg in human serum and plasma [potassium ethylenediaminetetraacetic acid (EDTA), lithium or sodium heparinized].
Baseline was Day 1, before start of study drug.
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Baseline, Weeks 24, 48, and 96
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Number of Participants With Treatment Emergent Serious Adverse Events (SAEs) on Treatment, and Discontinuation of Study Drug Due to Adverse Events (AE) - Treated Population
Délai: Day 1 to last dose of study drug plus 5 days; up to Week 96
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AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment.
SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Treatment-related=having certain, probable, possible, or missing relationship to study drug.
Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death.
On-treatment = on Day 1 through last dose of study therapy + 5 days.
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Day 1 to last dose of study drug plus 5 days; up to Week 96
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Number of Participants With Emergence of Genotypic Resistance to Study Drugs at Weeks 48 and 96- Treated Population
Délai: Baseline to Weeks 48, 96
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Testing of HBV genotype was performed at baseline for all treated patients and for participants at Weeks 48 and 96 with primary non-response or virologic breakthrough.
Emergent genotypic resistance to study drugs was defined as follows: Emergent = not detected at baseline; entecavir (ETV) resistance (ETVr): participant's sample was to have rtM204V/I/S and any substitution at rtT184, rtS202, or rtM250; tenofovir (TDF) resistance (TDFr) which was based on adefovir (ADV)-mutations: participant's sample was to have rtA181T/V, rtN236T, or (rtA194T and rtM204V/I/S).
Primary non-response was defined as < 1 log10 decrease in HBV DNA from baseline on treatment at or after Week 12. Virologic breakthrough was defined as ≥ 1 log10 increase in HBV DNA over nadir on treatment, either confirmed or last on-treatment followed by discontinuation of study therapy.
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Baseline to Weeks 48, 96
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Number of Participants on Treatment With Study Drug With Laboratory Test Abnormalities Meeting Selected Criteria on Treatment - Treated Population
Délai: Day 1 to last dose of study drug plus 5 days; up to Week 96
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Selected criteria presented in each category.
Upper limit of normal among all laboratory ranges (ULN); Baseline (BL); alanine transaminase (ALT); milligram per deciliter (mg/dL); milliliters per minute (mL/min); greater than (>);greater than, equal to (>=); less than (<).
Creatinine data presented below were confirmed, ie, at least 2 consecutive values.
On-treatment = after Day 1 through last dose of study therapy + 5 days.
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Day 1 to last dose of study drug plus 5 days; up to Week 96
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
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.
Liens utiles
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
1 mai 2010
Achèvement primaire (Réel)
1 novembre 2012
Achèvement de l'étude (Réel)
1 février 2014
Dates d'inscription aux études
Première soumission
3 février 2010
Première soumission répondant aux critères de contrôle qualité
4 février 2010
Première publication (Estimation)
5 février 2010
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
15 décembre 2014
Dernière mise à jour soumise répondant aux critères de contrôle qualité
25 novembre 2014
Dernière vérification
1 novembre 2014
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies du système digestif
- Infections par virus à ARN
- Maladies virales
- Infections
- Infections transmissibles par le sang
- Maladies transmissibles
- Maladies du foie
- Hépatite, virale, humaine
- Infections à Hépadnaviridae
- Infections par le virus de l'ADN
- Infections à entérovirus
- Infections à Picornaviridae
- Hépatite B
- Hépatite
- Hépatite A
- Hépatite B chronique
- Hépatite chronique
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents antiviraux
- Inhibiteurs de la transcriptase inverse
- Inhibiteurs de la synthèse des acides nucléiques
- Inhibiteurs d'enzymes
- Agents anti-VIH
- Agents antirétroviraux
- Ténofovir
- Entécavir
Autres numéros d'identification d'étude
- AI463-203
- 2009-015705-40 (Numéro EudraCT)
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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