An Exploratory Study of Telaprevir in Treatment-Naive Participants With Chronic Genotype 4 Hepatitis C Virus Infection
27 août 2013 mis à jour par: Tibotec BVBA
A Phase IIa Randomized, Partially Blinded Trial of Telaprevir (VX-950) in Treatment-Naive Subjects With Chronic Genotype 4 Hepatitis C Infection
The purpose of this study is to evaluate the activity and safety of telaprevir on Hepatitis C Virus (HCV) Genotype 4, alone or in combination with standard therapy, that is, pegylated-interferon-alfa-2a and ribavirin in treatment-naive (never been treated before with antiretroviral therapy) participants.
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Description détaillée
This is a Phase 2a, partially-blind, randomized (study drug assigned by chance) and multiple-dose study to evaluate the activity and safety of telaprevir on HCV early viral kinetics in treatment-naive participants who are chronically infected with HCV Genotype 4. The study consists of 4 parts: Screening period (6-week); Investigational Treatment period (consisting of 2-week treatment with telaprevir or telaprevir+standard treatment or placebo); Standard Treatment period (consists of 46 or 48-week standard treatment); and Follow-up period (24-week).
The activity of telaprevir will be evaluated by early viral kinetic parameters along with viral response and pharmacokinetic assessments during the investigational treatment phase.
Participants' safety will be monitored throughout the study.
Type d'étude
Interventionnel
Inscription (Réel)
24
Phase
- Phase 2
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 à 65 ans (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria: - Participant has chronic Genotype 4 Hepatitis C infection
- Plasma hepatitis C virus (HCV) ribonucleic acid (RNA) level greater than 10,000 International unit per milliliter (IU/mL) at Screening
- Participant never received treatment for HCV
- Participant was to be in good health (besides HCV infection), in the opinion of the Investigator, judged on the basis of medical history and physical examination (including vital signs and screening electrocardiogram [ECG]), with any chronic medical conditions under stable medical control
- Participant had to be willing to refrain from the concomitant use of any medications or substances Exclusion Criteria: - Participants with history or evidence of cirrhosis or history of suspicion of alcohol, barbiturate, or amphetamine recreational or narcotic drug use, which in the Investigator's opinion would compromise the participant's safety and/or compliance with study procedures
- Participant has human immunodeficiency virus (HIV) or hepatitis B virus (HBV) co-infection
- Female participants who are pregnant, or planning to become pregnant, or breastfeeding, and partners of female participants who are pregnant or breastfeeding
- Participant has hypersensitivity to tartrazine
- Participant had participated in any clinical trial for an investigational drug within 90 days before drug administration or participated in more than 2 drug studies in the last 12 months
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 |
|---|---|
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Expérimental: Telaprevir and then Pegylated-interferon-alfa-2a+Ribavirin
Telaprevir 750 milligram (mg) tablet will be administered three times a day orally for 2 weeks and after that pegylated-interferon-alfa-2a (180 microgram [mcg] subcutaneous injection [injected under the skin by way of a needle], once weekly) and ribavirin (1000-1200 mg as oral tablet daily) will be administered from Week 2 to 50.
|
Telaprevir 750 milligram (mg) tablet will be administered three times a day orally for 2 weeks.
Pegylated-interferon-alfa-2a (180 microgram [mcg] subcutaneous injection, once weekly) will be administered from Week 1 to Week 48 or 50.
Ribavirin (1000-1200 mg as oral tablet daily) will be administered from Week 1 to Week 48 or 50.
|
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Expérimental: Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin
Telaprevir 750 mg tablet will be administered three times a day orally for 2 weeks along with pegylated-interferon-alfa-2a (180 mcg subcutaneous injection, once weekly) and ribavirin (1000-1200 mg as oral tablet daily), from Week 1 to 48.
|
Telaprevir 750 milligram (mg) tablet will be administered three times a day orally for 2 weeks.
Pegylated-interferon-alfa-2a (180 microgram [mcg] subcutaneous injection, once weekly) will be administered from Week 1 to Week 48 or 50.
Ribavirin (1000-1200 mg as oral tablet daily) will be administered from Week 1 to Week 48 or 50.
|
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Comparateur actif: Placebo+Pegylated-interferon-alfa-2a+Ribavirin
Matching placebo tablet to telaprevir will be administered three times a day orally for 2 weeks along with pegylated-interferon-alfa 2a (180 mcg subcutaneous injection, once weekly) and ribavirin (1000-1200 mg as oral tablet daily), from Week 1 to 48.
|
Pegylated-interferon-alfa-2a (180 microgram [mcg] subcutaneous injection, once weekly) will be administered from Week 1 to Week 48 or 50.
Ribavirin (1000-1200 mg as oral tablet daily) will be administered from Week 1 to Week 48 or 50.
Matching placebo tablet to telaprevir was administered three times a day orally for 2 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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Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Day 15
Délai: Baseline and Day 15
|
The plasma HCV RNA levels were used to assess the antiviral activity which included viral response as either undetectable HCV RNA (that is no HCV target was detected in the plasma sample) or less than 25 International unit per milliliter (IU/mL) of HCV RNA (that is Plasma sample contained HCV RNA at a concentration below the limit of quantification [LLOQ=25 IU/mL] of the viral load assay).
Plasma HCV RNA levels were measured using the COBAS TaqMan HCV test Version 2.0.
This assay used real-time reverse transcription-polymerase chain reaction (RT-PCR) methodology.
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Baseline and Day 15
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Percentage of Participants With Viral Response (Undetectable HCV RNA)
Délai: Day 15 up to EOT (Week 48/50 or early discontinuation)
|
Viral response was either defined as having undetectable HCV RNA (that is, no HCV RNA was detected in the participants' plasma samples) or less than 25 IU/mL HCV RNA from Day 15 up to end of treatment (EOT), that is Week 48/50 or early discontinuation.
In Week x/y, where, x represents time frame for Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin and Placebo+Pegylated-interferon-alfa-2a+Ribavirin and; y represents time frame for Telaprevir and Pegylated-interferon-alfa-2a+Ribavirin treatment group.
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Day 15 up to EOT (Week 48/50 or early discontinuation)
|
|
Median Time to First Viral Response (Undetectable HCV RNA)
Délai: Up to Week 48/50
|
Time to first viral response (Undetectable HCV RNA) is defined as the number of days since the start of study medication until first time negative HCV RNA level that is less than 25 IU/mL was detected.
|
Up to Week 48/50
|
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Number of Participants With Viral Breakthrough (Detectable HCV RNA)
Délai: Day 8, Day 12, Day 15, Week 24/26 and Week 36/38
|
Viral breakthrough was defined as having a confirmed increase greater than 1 log 10 in HCV RNA level from the lowest level reached, or a confirmed level of HCV RNA greater than 100 IU/mL in participants whose HCV RNA had previously become undetectable [less than 25 IU/mL]).
In Week x/y, where, x represents time frame for Telaprevir+pegylated-interferon-alfa-2a+Ribavirin and Placebo+pegylated-interferon-alfa-2a+Ribavirin and y represents time frame for Telaprevir and then Pegylated-interferon-alfa-2a+Ribavirin treatment group.
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Day 8, Day 12, Day 15, Week 24/26 and Week 36/38
|
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Percentage of Participants With Sustained Viral Response (SVR)
Délai: Week 12 and 24 after the last dose of study medication
|
Sustained viral response was defined as having undetectable HCV RNA at EOT (Week 48/50 or early discontinuation) and no confirmed detectable HCV RNA levels between EOT and 12 weeks (SVR12) and 24 weeks (SVR24) after the last dose of study medication.
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Week 12 and 24 after the last dose of study medication
|
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Percentage of Participants With Relapse
Délai: Week 24 after EOT (Week 48/50 or early discontinuation)
|
Relapse was defined as having confirmed detectable HCV RNA during the 24-week follow-up period in participants who had undetectable HCV RNA at EOT (Week 48/50 or early discontinuation).
Participants who dropped out between 24-week follow-up after EOT were not evaluated for relapse.
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Week 24 after EOT (Week 48/50 or early discontinuation)
|
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Area Under the Serum Concentration-Time Curve (AUC)
Délai: Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15
|
The AUC is a measure of the serum concentration-time curve, calculated by the lin-up/log-down method.
|
Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15
|
|
Maximum Serum Concentration (Cmax) of Telaprevir
Délai: Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15
|
The Cmax is the maximum observed serum concentration, which was measured at Day 1 and 15 for telaprevir and then pegylated-interferon-alfa-2a+Ribavirin (reference) and telaprevir+pegylated-interferon-alfa-2a+Ribavirin (test).
|
Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15
|
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Pre-Dose Serum Concentration (C[0h]) of Telaprevir
Délai: 0 hour (pre-dose) at Day 15
|
The C(0h) is the pre-dose serum concentration of telaprevir and then pegylated-interferon-alfa-2a+Ribavirin (reference) and telaprevir+pegylated-interferon-alfa-2a+Ribavirin (test).
|
0 hour (pre-dose) at Day 15
|
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Minimum Serum Concentration (Cmin) of Telaprevir on Day 15
Délai: Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 15
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The Cmin is the minimum serum concentration between 0 hour and τ (τ=dosing interval) of telaprevir and then pegylated-interferon-alfa-2a+Ribavirin (reference) and telaprevir+pegylated-interferon-alfa-2a+Ribavirin (test).
Cmin on Day 15 is reported here.
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Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 15
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Time to Reach the Maximum Serum Concentration (Tmax) of Telaprevir
Délai: Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15
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The tmax is the time to reach maximum observed serum concentration of telaprevir and then pegylated-interferon-alfa-2a+Ribavirin (reference) and pegylated-interferon-alfa-2a+Ribavirin (test).
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Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15
|
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Average Steady-State Serum Concentration (Css,av) of Telaprevir
Délai: Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15
|
The Average steady-state serum concentration (Css,av) was calculated by AUC/τ at steady-state (τ=dosing interval) of telaprevir and then pegylated-interferon-alfa-2a+Ribavirin (reference) and telaprevir+pegylated-interferon-alfa-2a+Ribavirin (test).
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Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15
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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 janvier 2008
Achèvement primaire (Réel)
1 janvier 2010
Achèvement de l'étude (Réel)
1 janvier 2010
Dates d'inscription aux études
Première soumission
20 décembre 2007
Première soumission répondant aux critères de contrôle qualité
26 décembre 2007
Première publication (Estimation)
27 décembre 2007
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
9 septembre 2013
Dernière mise à jour soumise répondant aux critères de contrôle qualité
27 août 2013
Dernière vérification
1 août 2013
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
- Infections à entérovirus
- Infections à Picornaviridae
- Hépatite
- Hépatite A
- Hépatite C
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents antiviraux
- Antimétabolites
- Agents antinéoplasiques
- Facteurs immunologiques
- Interférons
- Interféron-alpha
- Ribavirine
- Peginterféron alfa-2a
- Interféron alpha-2
Autres numéros d'identification d'étude
- CR013714
- VX-950-TiDP24-C210
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