An Efficacy and Safety Study of Simeprevir and Sofosbuvir With and Without Ribavirin in Participants With Recurrent Genotype 1 Hepatitis C Post-Orthotopic Liver Transplant (GALAXY)
10 novembre 2016 mis à jour par: Janssen Scientific Affairs, LLC
A Phase 2 Open-Label Study in Patients With Recurrent Genotype 1 Hepatitis C Post-Orthotopic Liver Transplant to Explore the Safety And Efficacy of Simeprevir and Sofosbuvir With and Without Ribavirin
The purpose of this study is to evaluate sustained virologic response 12 weeks after the end of treatment (SVR12) following 12 weeks of simeprevir plus sofosbuvir with and without ribavirin (RBV) and 24 weeks of simeprevir plus sofosbuvir without RBV in post orthotopic liver transplant participants with recurrent hepatitis (inflammation of the liver) C virus (HCV) Genotype 1 infection.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
This is a Phase 2, multicenter (when more than one hospital or medical school team work on a medical research study), partially randomized (study drug is assigned by chance), and open-label (all people know the identity of the intervention) study to explore the safety and efficacy of simeprevir plus sofosbuvir.
The study will consist of a screening period (Screening and Baseline), followed by randomization.
First 33 non-cirrhotic participants will be randomly assigned in a ratio of 1:1:1 into 1 of 3 treatment arms, and up to 12 cirrhotic participants will be enrolled and all will be assigned to Arm 3.
All participants in treatment Arms 1 and 2 will return for treatment visits at Weeks 1, 2, 4, 8, 12, and post-treatment follow-up visits on Weeks 16 and 24.
All participants in treatment Arm 3 will return for treatment visits at Weeks 1, 2, 4, 8, 12, 16, 20, and 24, and post-treatment follow-up visits on Weeks 28 and 36.
Participants will receive simeprevir plus sofosbuvir and RBV for a 12-week treatment period in Arm 1, simeprevir plus sofosbuvir without RBV for a 12-week treatment period in Arm 2 and simeprevir plus sofosbuvir for a 24-week treatment period in Arm 3. Efficacy will primarily be evaluated by SVR12.
Participants' safety will be monitored throughout the study.
Type d'étude
Interventionnel
Inscription (Réel)
46
Phase
- Phase 2
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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Colorado
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Aurora, Colorado, États-Unis
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Florida
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Gainesville, Florida, États-Unis
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Miami, Florida, États-Unis
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Massachusetts
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Boston, Massachusetts, États-Unis
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Michigan
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Ann Arbor, Michigan, États-Unis
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Detroit, Michigan, États-Unis
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New York
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New York, New York, États-Unis
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North Carolina
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Durham, North Carolina, États-Unis
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Pennsylvania
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Philadelphia, Pennsylvania, États-Unis
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Pittsburgh, Pennsylvania, États-Unis
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Texas
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Dallas, Texas, États-Unis
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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:
- Participant must be infected with Hepatitis C virus (HCV) Genotype 1 (1a or 1b) with Baseline HCV ribonucleic acid (RNA) greater than (>) 10,000 international unit per milliliter (IU/mL). Retesting of HCV RNA to assess eligibility will be allowed once, using an unscheduled visit during the Screening period
- Participant must have had an orthotopic liver transplant greater than or equal to (>=) 6 months to 15 years prior to enrollment
- Participant must have had primary liver transplant
- Participant must be on a stable immunosuppressive regimen for at least 3 months prior to the Screening visit. Immunosuppression regimens may include calcineurin inhibitors (for example, tacrolimus), mammalian target of rapamycin (mTOR) inhibitor, mycophenolate mofetil, prednisone, prednisolone less than or equal to (<=) 5 milligram per day (mg/day), other corticosteroids (except systemic dexamethasone), sirolimus, everolimus, or azathioprine. Stable immunosuppression includes normal adjustment of immunosuppressant dose but excludes changes in immunosuppressant medication and/or treatment of rejection.
- Participant's renal function as measured by the Cockcroft Gault formula must be >30 milliliter per minute (mL/min)
Exclusion Criteria:
- Participants received prior treatment with an investigational or Food and Drug Administration (FDA) approved direct-acting antiviral drug for the treatment of hepatitis C. Prior HCV treatment with interferon or peginterferon with or without ribavirin (RBV) is allowed but must have been completed at least 3 months prior to Screening
- Participants with hepatic decompensation defined by any of the following: 1) Any post-liver transplant clinical signs including ascites, hepatic encephalopathy, and/or evidence of varices with or without variceal bleeding, and 2) Child-Turcotte-Pugh (CTP) score >=7
- Participant has (post-transplant) any underlying serious or life-threatening condition, such as severe uncontrolled cardiopulmonary disease, vascular disease, rheumatologic condition, renal failure, dialysis, ongoing systemic infection, uncontrolled malignancy, or other serious illness that would compromise adherence to medications and ability to comply with all aspects of the study protocol
- Any other active, clinically significant disease or clinically significant findings during the Screening period of medical history, physical examination, laboratory testing, or electrocardiogram (ECG) recording that, in the investigator's opinion, would compromise the participant's safety or could interfere with the participant participating in and completing the study. Retesting of laboratory results that lead to exclusion will be allowed once using an unscheduled visit during the Screening period to assess eligibility
- Participant is a woman who is pregnant, breast-feeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of ribavirin (or longer when dictated by local regulations)
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: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
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Expérimental: Simeprevir plus Sofosbuvir plus Ribavirin (Arm 1)
Participants will be administered simeprevir capsule 150 milligram (mg), sofosbuvir 400 mg tablet, and ribavirin 2 x 200 mg tablets (for participants weighing less than 75 kilogram [kg]) or 3 x 200 mg tablets (for participants weighing more than 75 kg weight), orally once daily up to 12 weeks.
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Participants will be administered simeprevir capsule 150 mg orally once daily up to 12 weeks.
Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 12 weeks.
Participants will be administered ribavirin 2 x 200 mg tablets (for participants weighing less than 75 kilogram ([kg]) or 3 x 200 mg tablets (for participants weighing more than 75 kg) orally once daily up to 12 weeks.
Participants will be administered simeprevir capsule 150 mg orally once daily up to 24 weeks.
Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 24 weeks.
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Expérimental: Simeprevir plus Sofosbuvir (Arm 2)
Participants will be administered simeprevir capsule 150 mg and sofosbuvir 400 mg tablet orally once daily up to 12 weeks.
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Participants will be administered simeprevir capsule 150 mg orally once daily up to 12 weeks.
Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 12 weeks.
Participants will be administered simeprevir capsule 150 mg orally once daily up to 24 weeks.
Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 24 weeks.
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Expérimental: Simeprevir plus Sofosbuvir (Arm 3)
Participants will be administered simeprevir 150 mg capsule and sofosbuvir 400 mg tablet orally once daily 24 weeks.
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Participants will be administered simeprevir capsule 150 mg orally once daily up to 12 weeks.
Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 12 weeks.
Participants will be administered simeprevir capsule 150 mg orally once daily up to 24 weeks.
Participants will be administered sofosbuvir 400 mg tablet orally once daily up to 24 weeks.
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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 Sustained Virologic Response After 12 Weeks of end of Treatment (SVR12)
Délai: Week 24 or Week 36
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Participants will be considered to have achieved SVR12 if the hepatitis C virus ribonucleic acid (HCV RNA) is less than (<) 15 international unit per milliliter (IU/mL) (detectable or undetectable) at 12 weeks after the end of treatment.
End of treatment is at Week 12 (for Arms 1 and 2) or Week 24 (for Arm 3); therefore, outcome will be measured at Week 24 (for Arms 1 and 2) or Week 36 (for Arm 3).
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Week 24 or Week 36
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Percentage of Participants With Sustained Virologic Response After 4 Weeks of end of Treatment (SVR4)
Délai: Week 16 (for Arms 1 and 2) and Week 28 (for Arm 3)
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Participants will be considered to have achieved SVR4 if the hepatitis C virus ribonucleic acid (HCV RNA) is <15 IU/mL (detectable or undetectable) at 4 weeks after the end of treatment.
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Week 16 (for Arms 1 and 2) and Week 28 (for Arm 3)
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Percentage of Participants With Undetectable Hepatitis C Virus Ribonucleic Acid (HCV-RNA)
Délai: Weeks 2, 4, 8 and 12 (for all treatment arms) and Weeks 16 20, and 24 (for Arm 3)
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Plasma HCV RNA will be determined using an in vitro nucleic acid amplification test for the quantification of HCV RNA in human plasma using a sensitive assay (COBAS® AmpliPrep/COBAS® TaqMan® HCV Test v2.0 , lower limit of quantification = limit of detection = 15 IU/mL).
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Weeks 2, 4, 8 and 12 (for all treatment arms) and Weeks 16 20, and 24 (for Arm 3)
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Percentage of Participants With Viral Breakthrough
Délai: Baseline up to Week 24 (for Arms 1 and 2) and Baseline up to Week 36 (for Arm 3)
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Viral breakthrough is defined as confirmed greater than (>) 1.0 Log10 increase in HCV RNA from nadir or confirmed HCV RNA >100 IU/mL in participants who had previously achieved HCV RNA <15 IU/mL.
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Baseline up to Week 24 (for Arms 1 and 2) and Baseline up to Week 36 (for Arm 3)
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Percentage of Participants With Viral Relapse
Délai: Baseline up to Week 24 (for Arms 1 and 2) and Baseline up to Week 36 (for Arm 3)
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Participants will be considered to have viral relapse if they meet the following conditions: 1) HCV RNA <15 IU/mL (undetectable) at the end of treatment; and 2) HCV RNA greater than or equal to (>=) 15 IU/mL during the post-treatment follow-up period.
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Baseline up to Week 24 (for Arms 1 and 2) and Baseline up to Week 36 (for Arm 3)
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Change From Baseline in Hepatitis C Symptom and Impact Questionnaire Version 4 (HCV-SIQv4) Score at Week 24 (for Arms 1 and 2) and Week 36 (for Arm 3)
Délai: Baseline, Week 24 (for Arms 1 and 2) and Week 36 (for Arm 3)
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The HCV-SIQv4 is a self-administered questionnaire containing 33 items classified as 3 categories of scores: 1) Symptom severity score (sum of responses to 29 questions to assess severity or frequency of symptoms associated with HCV or its treatment; 2) Time missed from work/school (sum of responses to 3 questions regarding the impact of symptoms on work/school attendance); 3) Daily activity score (response to 1 question regarding the impact of symptoms on daily activities).
Higher HCV SIQv4 scores indicate worse symptom severity, more time missed from work/school, and more impairment in daily activities, respectively.
The total score is the sum of scores of these 3 categories.
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Baseline, Week 24 (for Arms 1 and 2) and Week 36 (for Arm 3)
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Change From Baseline in EuroQol 5 - Dimension (EQ-5D) Questionnaire Score at Weeks 4, 8, 12, 16, 20, 24 (for all treatment arms) and Week 36 (for Arm 3)
Délai: Baseline, Weeks 4, 8, 12, 16, 20, 24 (for all treatment arms) and Week 36 (for Arm 3)
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The EQ-5D questionnaire is a brief, generic health-related quality of life assessment (HRQOL) that can also be used to incorporate participant preferences into health economic evaluations.
The EQ-5D questionnaire assesses HRQOL in terms of degree of limitation on 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) and as overall health using a "thermometer" visual analog scale with response options ranging from 0 (worst imaginable health) to 100 (best imaginable health).
Lower scores indicate worsening.
EQ-5D scores include EQ-5D valuation index score (a weighted scoring of the 5 dimension scores with a possible range from 0 to 1), EQ-5D visual analog scale (VAS) is a 20 centimeter (cm) vertical VAS with scores ranging from 0 (worst imaginable health) to 100 (perfect health), and EQ5D descriptive system scores (five scores reflecting each of the 5 EQ-5D health dimensions ranging from 0 [no limitation] to 4 [incapacity]).
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Baseline, Weeks 4, 8, 12, 16, 20, 24 (for all treatment arms) and Week 36 (for Arm 3)
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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.
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 août 2014
Achèvement primaire (Réel)
1 novembre 2015
Achèvement de l'étude (Réel)
1 novembre 2015
Dates d'inscription aux études
Première soumission
10 juin 2014
Première soumission répondant aux critères de contrôle qualité
13 juin 2014
Première publication (Estimation)
17 juin 2014
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
11 novembre 2016
Dernière mise à jour soumise répondant aux critères de contrôle qualité
10 novembre 2016
Dernière vérification
1 novembre 2016
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
- Infections à Flaviviridae
- Hépatite, virale, humaine
- Hépatite
- Hépatite C
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents antiviraux
- Inhibiteurs d'enzymes
- Antimétabolites
- Inhibiteurs de protéase
- Sofosbuvir
- Ribavirine
- Siméprévir
Autres numéros d'identification d'étude
- CR104281
- TMC435HPC2009 (Autre identifiant: Janssen Scientific Affairs, LLC)
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 .