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A Study of TMC435 in Combination With Pegylated Interferon Alp\Fa-2a and Ribavirin in Patients Infected With Genotype 1 Hepatitis C Virus Who Never Received Treatment (PILLAR)

19. maj 2014 opdateret af: Tibotec Pharmaceuticals, Ireland

A Phase IIb, Randomized, Double-Blind, Placebo-Controlled Trial to Investigate the Efficacy, Tolerability, Safety and Pharmacokinetics of TMC435 as Part of a Treatment Regimen Including Peginterferon Alfa-2a and Ribavirin In Treatment-Naive Genotype 1 Hepatitis C-Infected Subjects

The purpose of this study is to evaluate the efficacy of 4 different regimens of TMC435 in combination with peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV), defined as the proportion of patients with sustained virologic response at Week 72 (patients with undetectable plasma HCV RNA [less than 25 IU per mL undetectable] at the end of treatment and at Week 72), compared to the control group receiving PegIFN and RBV in combination with TMC435-matched placebo.

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

This is a randomized (study medication assigned by chance), 5-arm, double-blind (neither investigator nor the participant knows the treatment that the participant receives), placebo-controlled (an inactive substance that is compared with the study medication to test whether the study medication has a real effect in clinical study) study to compare the efficacy, tolerability and safety of different TMC435 regimens combined with peginterferon alfa-2a (PegIFNα-2a) and ribavirin (RBV) versus PegIFNα-2a plus RBV alone in adult treatment-naive patients with chronic genotype 1 HCV infection. The study mainly consists of 3 phases: screening phase (approximately 6 weeks), treatment phase (up to 48 weeks), and follow up phase (up to 48 weeks). In the treatment phase, patients will be divided in to 5 different arms in a 1:1:1:1:1 randomized ratio. In treatment arms 1 and 2, patients will receive 12 weeks of therapy with TMC435 along with PegIFNα 2a and RBV followed by treatment with PegIFNα 2a, RBV, and TMC435-matched placebo. In treatment arms 3 and 4, patients will receive 24 weeks of therapy with TMC435, PegIFNα 2a, and RBV. In treatment arm 5 (control group), patients will receive PegIFNα 2a and RBV for 48 weeks and TMC435 matched placebo for the first 24 weeks. Collection of blood samples for efficacy evaluations will be done at scheduled visits throughout the study. Safety evaluations for adverse events, clinical laboratory tests, physical examination, vital signs and electrocardiogram will be monitored throughout the study. The total duration of the study will be up to approximately 72 weeks after initiation of treatment.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

386

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Australien
      • Concord, Australien
      • Darlinghurst, Australien
      • Fitzroy, Australien
      • Melbourne, Australien
      • Sydney, Australien
      • Woolloongabba N/A, Australien
  • Belgien
      • Brugge, Belgien
      • Brussels, Belgien
      • Bruxelles, Belgien
      • Edegem, Belgien
      • Gent, Belgien
      • Leuven, Belgien
      • Roeselare, Belgien
  • Canada
    • Alberta
      • Calgary, Alberta, Canada
    • Ontario
      • Toronto, Ontario, Canada
    • Quebec
      • Montreal, Quebec, Canada
  • Danmark
      • Aarhus, Danmark
      • Copenhagen, Danmark
      • Hvidovre N/A, Danmark
      • Kolding, Danmark
      • Odense N/A, Danmark
  • Den Russiske Føderation
      • Moscow, Den Russiske Føderation
      • Nizhny Novgorod, Den Russiske Føderation
      • Saint-Petersburg, Den Russiske Føderation
      • Samara, Den Russiske Føderation
      • Smolensk, Den Russiske Føderation
      • St Petersburg, Den Russiske Føderation
  • Forenede Stater
    • California
      • Los Angeles, California, Forenede Stater
    • Florida
      • Jacksonville, Florida, Forenede Stater
      • Orlando, Florida, Forenede Stater
      • Palm Harbor, Florida, Forenede Stater
    • Illinois
      • Chicago, Illinois, Forenede Stater
    • Louisiana
      • New Orleans, Louisiana, Forenede Stater
    • Minnesota
      • Saint Paul, Minnesota, Forenede Stater
    • New York
      • New York, New York, Forenede Stater
    • North Carolina
      • Chapel Hill, North Carolina, Forenede Stater
    • Ohio
      • Cincinnati, Ohio, Forenede Stater
    • Tennessee
      • Germantown, Tennessee, Forenede Stater
    • Virginia
      • Charlottesville, Virginia, Forenede Stater
  • Frankrig
      • Clichy, Frankrig
      • Creteil N/A, Frankrig
      • Grenoble, Frankrig
      • Lyon, Frankrig
      • Nice, Frankrig
      • Paris, Frankrig
      • Vandoeuvre Les Nancy, Frankrig
  • New Zealand
      • Auckland, New Zealand
      • Christchurch, New Zealand
      • Hamilton, New Zealand
  • Norge
      • Bergen, Norge
      • Nordbyhagen, Norge
      • Oslo, Norge
      • Tromsø, Norge
  • Polen
      • Bialystok, Polen
      • Bydgoszcz, Polen
      • Czeladz, Polen
      • Kielce, Polen
      • Lodz, Polen
      • Warschau, Polen
  • Spanien
      • Barcelona, Spanien
      • Madrid, Spanien
      • Sevilla N/A, Spanien
      • Valencia, Spanien
  • Tyskland
      • Berlin, Tyskland
      • Düsseldorf, Tyskland
      • Frankfurt A. M., Tyskland
      • Freiburg, Tyskland
      • Hamburg, Tyskland
      • Hannover, Tyskland
      • Köln, Tyskland
      • Stuttgart, Tyskland
      • Würzburg, Tyskland
  • Østrig
      • Wien, Østrig

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 70 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • Patients with documented chronic genotype-1 hepatitis C infection and with plasma HCV RNA of > 100,000 IU/mL at screening
  • Patients that have not been treated before for HCV
  • Patients that are of childbearing potential or have a partner of childbearing potential should agree to use 2 effective methods of contraception

Exclusion Criteria:

  • Patients with cirrhosis or evidence of hepatic decompensation
  • Co-infection with the human immunodeficiency virus (HIV)
  • Any contraindication to Pegasys or Copegus therapy
  • History of, or any current medical condition which could impact the safety of the patient in the study

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Randomiseret
  • Interventionel model: Parallel tildeling
  • Maskning: Firedobbelt

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: TMC435 75 mg 12 Wks + PR 24/48
Participants will receive TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo once daily and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Medicin: TMC435
TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.
Andre navne:
  • TMC 435
Medicin: Ribavirin (R)
Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.
Andre navne:
  • COPEGUS
Medicin: PegIFNα-2a (P)
PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.
Andre navne:
  • PEGASYS
Medicin: Placebo
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
Eksperimentel: TMC435 75 mg 24 Wks + PR 24/48
Participants will receive TMC435 75 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Medicin: TMC435
TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.
Andre navne:
  • TMC 435
Medicin: Ribavirin (R)
Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.
Andre navne:
  • COPEGUS
Medicin: PegIFNα-2a (P)
PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.
Andre navne:
  • PEGASYS
Medicin: Placebo
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
Eksperimentel: TMC435 150 mg 12 Wks + PR 24/48
Participants will receive TMC435 150 mg once daily with PegIFNα-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed Placebo and PR for 12 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Medicin: TMC435
TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.
Andre navne:
  • TMC 435
Medicin: Ribavirin (R)
Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.
Andre navne:
  • COPEGUS
Medicin: PegIFNα-2a (P)
PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.
Andre navne:
  • PEGASYS
Medicin: Placebo
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
Eksperimentel: TMC435 150 mg 24 Wks + PR 24/48
Participants will receive TMC435 150 mg once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks. Treatment with PR was stopped at Week 24 for participants who met response-guided treatment (RGT) criteria. All other participants continued PR until Week 48.
Medicin: TMC435
TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.
Andre navne:
  • TMC 435
Medicin: Ribavirin (R)
Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.
Andre navne:
  • COPEGUS
Medicin: PegIFNα-2a (P)
PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.
Andre navne:
  • PEGASYS
Medicin: Placebo
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
Placebo komparator: Placebo 24 Wks + PR48
Participants will receive Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Medicin: Ribavirin (R)
Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.
Andre navne:
  • COPEGUS
Medicin: PegIFNα-2a (P)
PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.
Andre navne:
  • PEGASYS
Medicin: Placebo
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Procentdelen af ​​deltagere, der opnår et vedvarende virologisk respons i uge 72 (SVRW72)
Tidsramme: Uge 72
Tabellen nedenfor viser procentdelen af ​​deltagere i hver behandlingsgruppe, der opnåede en SVRW72, defineret som procentdelen af ​​deltagere med ikke-detekterbare plasma hepatitis C-virus-ribonukleinsyreniveauer ved behandlingens afslutning (EOT) og ved uge 72.
Uge 72

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Procentdelen af ​​deltagere, der opnår en hurtig virologisk respons (RVR)
Tidsramme: Uge 4
Tabellen nedenfor viser procentdelen af ​​deltagere i hver behandlingsgruppe, der opnåede en RVR, defineret som havende ikke-detekterbare hepatitis C-virus-ribonukleinsyreniveauer efter at have modtaget 4 ugers behandling.
Uge 4
Procentdelen af ​​deltagere, der opnår en komplet tidlig virologisk respons (cEVR)
Tidsramme: Uge 12
Tabellen nedenfor viser procentdelen af ​​deltagere i hver behandlingsgruppe, der havde en cEVR, defineret som havende ikke-detekterbare hepatitis C-virus-ribonukleinsyreniveauer i uge 12.
Uge 12
The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Undetectable During Treatment and Follow-up
Tidsramme: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
The table below shows the percentage of participants in each treatment group who achieved plasma HCV RNA levels of less than 25 IU/mL undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).
Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
The Percentage of Participants Who Achieved Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Less Than 25 IU/mL Detectable or Undetectable During Treatment and Follow-up
Tidsramme: Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA less than 25 IU/mL detectable or undetectable at selected time points during treatment, follow-up, and at end of treatment (EOT).
Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
The Percentage of Participants Achieving Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels of Greater Than or Equal to 2 log10 Drop During Treatment
Tidsramme: Baseline (Day 1) and Weeks, 2, 4, 8, and 12
The table below shows the percentage of participants in each treatment group who achieved plasma levels of HCV RNA greater than or equal to 2 log10 drop from Baseline at selected time points during treatment.
Baseline (Day 1) and Weeks, 2, 4, 8, and 12
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
Tidsramme: Week 48 or 72
The table below shows the percentage of participants in each treatment group who achieved a SVR24, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 24 weeks after the EOT.
Week 48 or 72
The Percentage of Participants Achieving an Early Virologic Response (EVR)
Tidsramme: Baseline (Day 1) and Week 12
The table below shows the percentage of participants who achieved an EVR, defined as having a change from baseline in plasma Hepatitis C virus ribonucleic acid of 2 log10 at Week 12.
Baseline (Day 1) and Week 12
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Tidsramme: Up to Week 36 or 52
The table below shows the percentage of participants who achieved undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 12 Weeks after the EOT.
Up to Week 36 or 52
Number of Participants With Viral Breakthrough
Tidsramme: Week 24 or 48
The table below shows the number of participants in each treatment group who experienced viral breakthrough during the TMC435 treatment period of the study, defined as a confirmed increase of more than 1 log10 IU/mL in plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached or a confirmed value of plasma HCV RNA more than 100 IU/mL in participants whose plasma HCV RNA level had previously been below the limit of quantification (less than 25 IU/mL detectable or undetectable).
Week 24 or 48
The Number of Participants With Viral Relapse
Tidsramme: Up to Week 72
The table below shows the number of participants who experienced viral relapse, defined as a confirmed detectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) level during the follow-up period in participants with undetectable plasma HCV RNA (less than 25 IU/mL undetectable) at the end of treatment.
Up to Week 72
The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT)
Tidsramme: Baseline (Day 1) up to Week 24 or 48
The table below shows the number of participants with abnormal ALT levels at Baseline who achieved ALT levels within the normal range at the EOT.
Baseline (Day 1) up to Week 24 or 48
Plasma Concentrations of TMC435
Tidsramme: Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
The table below shows median (range) predose plasma concentration (C0h) values and median (range) average steady-state plasma concentration (Css,av) values for participants in each of the 4 TMC435 treatment groups.
Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
Tidsramme: Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
The table below shows the median (range) AUC24h values for TMC435 for participants in each of the 4 TMC435 treatment groups. Two blood samples taken at least 2 hours apart from each other for determination of TMC435 plasma pharmacokinetics were obtained in all participants on Weeks 2, 4, 8, 12, 16, and 24 to obtain Bayesian estimates of TMC435 AUC24h (overall exposure).
Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Tibotec Pharmaceuticals, Ireland

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. juni 2009

Primær færdiggørelse (Faktiske)

1. april 2010

Studieafslutning (Faktiske)

1. april 2011

Datoer for studieregistrering

Først indsendt

16. april 2009

Først indsendt, der opfyldte QC-kriterier

16. april 2009

Først opslået (Skøn)

17. april 2009

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Skøn)

16. juni 2014

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

19. maj 2014

Sidst verificeret

1. maj 2014

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CR015799
  • TMC435-TiDP16-C205 (Anden identifikator: Tibotec Pharmaceuticals, Ireland)
  • 2008-007147-13 (EudraCT nummer)

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

Kliniske forsøg med Hepatitis C

Kliniske forsøg med TMC435

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Betingelser

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Placeringer

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