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Hepatitis CPhase 2PILLARNCT00882908

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

A Phase 2 study testing TMC435, Ribavirin (R) and PegIFNα-2a (P) in people with Hepatitis C, run by Tibotec Pharmaceuticals, Ireland at 71 sites in 13 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Hepatitis C
What is being tested?
TMC435, Ribavirin (R) and PegIFNα-2a (P)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
386 participants
Where
71 sitesin 13 countries
Study dates
Jun 2009to Apr 2011
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

71 sites in 13 countries.

71 sites in 13 countries

United States12 sites

  • Study site

    Chapel Hill, North Carolina

  • Study site

    Charlottesville, Virginia

  • Study site

    Chicago, Illinois

  • Study site

    Cincinnati, Ohio

  • Study site

    Germantown, Tennessee

  • Study site

    Jacksonville, Florida

  • Study site

    Los Angeles, California

  • Study site

    New Orleans, Louisiana

  • Study site

    New York, New York

  • Study site

    Orlando, Florida

  • Study site

    Palm Harbor, Florida

  • Study site

    Saint Paul, Minnesota

Other trials in United States

Germany9 sites

  • Study site

    Berlin

  • Study site

    Cologne

  • Study site

    Düsseldorf

  • Study site

    Frankfurt A. M.

  • Study site

    Freiburg im Breisgau

  • Study site

    Hamburg

  • Study site

    Hanover

  • Study site

    Stuttgart

  • Study site

    Würzburg

Other trials in Germany

France7 sites

  • Study site

    Clichy

  • Study site

    Créteil

  • Study site

    Grenoble

  • Study site

    Lyon

  • Study site

    Nice

  • Study site

    Paris

  • Study site

    Vandœuvre-lès-Nancy

Other trials in France

Australia6 sites

  • Study site

    Concord

  • Study site

    Darlinghurst

  • Study site

    Fitzroy

  • Study site

    Melbourne

  • Study site

    Sydney

  • Study site

    Woolloongabba

Other trials in Australia

Belgium6 sites

  • Study site

    Bruges

  • Study site

    Brussels

  • Study site

    Edegem

  • Study site

    Ghent

  • Study site

    Leuven

  • Study site

    Roeselare

Other trials in Belgium

Poland6 sites

  • Study site

    Bialystok

  • Study site

    Bydgoszcz

  • Study site

    Czeladź

  • Study site

    Kielce

  • Study site

    Lodz

  • Study site

    Warsaw

Other trials in Poland

Denmark5 sites

  • Study site

    Aarhus

  • Study site

    Copenhagen

  • Study site

    Hvidovre

  • Study site

    Kolding

  • Study site

    Odense

Other trials in Denmark

Russia5 sites

  • Study site

    Moscow

  • Study site

    Nizhny Novgorod

  • Study site

    Saint Petersburg

  • Study site

    Samara

  • Study site

    Smolensk

Other trials in Russia

Norway4 sites

  • Study site

    Bergen

  • Study site

    Nordbyhagen

  • Study site

    Oslo

  • Study site

    Tromsø

Other trials in Norway

Spain4 sites

  • Study site

    Barcelona

  • Study site

    Madrid

  • Study site

    Seville

  • Study site

    Valencia

Other trials in Spain

Canada3 sites

  • Study site

    Calgary, Alberta

  • Study site

    Montreal, Quebec

  • Study site

    Toronto, Ontario

Other trials in Canada

New Zealand3 sites

  • Study site

    Auckland

  • Study site

    Christchurch

  • Study site

    Hamilton

Other trials in New Zealand

Austria1 site

  • Study site

    Vienna

Other trials in Austria

About this study

Official title: 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.

Read the detailed description

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.

Conditions
Hepatitis C
Being tested
TMC435, Ribavirin (R), PegIFNα-2a (P), Placebo
Keywords
Hepatitis C, TMC435, Peginterferon alpha-2a, PegIFNalpha-2a, RBV, Ribavirin, Placebo
Medical subject headings
Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TMC435Drug

    Also called TMC 435

    TMC435 will be administered as one or two 75 mg capsules orally, once daily, for 12 or 24 weeks.

  • Ribavirin (R)Drug

    Also called COPEGUS

    Ribavirin (R) will be administered as 200 mg tablets (5 to 6 tablets) orally, twice daily, for 48 weeks.

  • PegIFNα-2a (P)Drug

    Also called PEGASYS

    PegIFNα-2a (P) 180 micrograms will be administered as a subcutaneous (under the skin) injection, once weekly for 48 weeks.

  • PlaceboDrug

    Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.

Study groups in NCT00882908
Study groupRoleWhat they receive
TMC435 75 mg 12 Wks + PR 24/48ExperimentalParticipants 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.
Receives: Drug: TMC435; Drug: Ribavirin (R); Drug: PegIFNα-2a (P); Drug: Placebo
TMC435 75 mg 24 Wks + PR 24/48ExperimentalParticipants 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.
Receives: Drug: TMC435; Drug: Ribavirin (R); Drug: PegIFNα-2a (P); Drug: Placebo
TMC435 150 mg 12 Wks + PR 24/48ExperimentalParticipants 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.
Receives: Drug: TMC435; Drug: Ribavirin (R); Drug: PegIFNα-2a (P); Drug: Placebo
TMC435 150 mg 24 Wks + PR 24/48ExperimentalParticipants 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.
Receives: Drug: TMC435; Drug: Ribavirin (R); Drug: PegIFNα-2a (P); Drug: Placebo
Placebo 24 Wks + PR48Placebo comparatorParticipants will receive Placebo once daily with PegIFNα-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.
Receives: Drug: Ribavirin (R); Drug: PegIFNα-2a (P); Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)

    The table below shows the percentage of participants in each treatment group who achieved a SVRW72, defined as the percentage of participants with undetectable plasma Hepatitis C virus ribonucleic acid levels at end of treatment (EOT) and at Week 72.

    Measured: Week 72

Secondary outcomes (13)

  1. 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

    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).

    Measured: Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)

  2. 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

    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).

    Measured: Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)

  3. 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

    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.

    Measured: Baseline (Day 1) and Weeks, 2, 4, 8, and 12

  4. The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)

    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.

    Measured: Week 48 or 72

  5. The Percentage of Participants Achieving a Rapid Virologic Response (RVR)

    The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having undetectable plasma Hepatitis C virus ribonucleic acid levels after receiving 4 weeks of treatment.

    Measured: Week 4

  6. The Percentage of Participants Achieving an Early Virologic Response (EVR)

    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.

    Measured: Baseline (Day 1) and Week 12

  7. The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)

    The table below shows the percentage of participants in each treatment group who had a cEVR, defined as having undetectable plasma Hepatitis C Virus ribonucleic acid levels at Week 12.

    Measured: Week 12

  8. The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)

    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.

    Measured: Up to Week 36 or 52

  9. Number of Participants With Viral Breakthrough

    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).

    Measured: Week 24 or 48

  10. The Number of Participants With Viral Relapse

    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.

    Measured: Up to Week 72

  11. The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT)

    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.

    Measured: Baseline (Day 1) up to Week 24 or 48

  12. Plasma Concentrations of TMC435

    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.

    Measured: Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24

  13. Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435

    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).

    Measured: Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2009 (estimated)
  2. Study startJun 2009
  3. Primary completionApr 2010
  4. Study completionApr 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
386 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00882908
Sponsor's protocol ID
CR015799
Other IDs
TMC435-TiDP16-C205, 2008-007147-13, 2008
Acronym
PILLAR
Status last verified
May 2014
First submitted
16 Apr 2009
Last updated
16 Jun 2014
Data monitoring committee
Yes

Publications

  • Lenz O, Verbinnen T, Fevery B, Tambuyzer L, Vijgen L, Peeters M, Buelens A, Ceulemans H, Beumont M, Picchio G, De Meyer S. Virology analyses of HCV isolates from genotype 1-infected patients treated with simeprevir plus peginterferon/ribavirin in Phase IIb/III studies. J Hepatol. 2015 May;62(5):1008-14. doi: 10.1016/j.jhep.2014.11.032. Epub 2014 Nov 28.

    PubMed 25445400

  • Scott J, Rosa K, Fu M, Cerri K, Peeters M, Beumont M, Zeuzem S, Evon DM, Gilles L. Fatigue during treatment for hepatitis C virus: results of self-reported fatigue severity in two Phase IIb studies of simeprevir treatment in patients with hepatitis C virus genotype 1 infection. BMC Infect Dis. 2014 Aug 26;14:465. doi: 10.1186/1471-2334-14-465.

    PubMed 25164700

  • Fried MW, Buti M, Dore GJ, Flisiak R, Ferenci P, Jacobson I, Marcellin P, Manns M, Nikitin I, Poordad F, Sherman M, Zeuzem S, Scott J, Gilles L, Lenz O, Peeters M, Sekar V, De Smedt G, Beumont-Mauviel M. Once-daily simeprevir (TMC435) with pegylated interferon and ribavirin in treatment-naive genotype 1 hepatitis C: the randomized PILLAR study. Hepatology. 2013 Dec;58(6):1918-29. doi: 10.1002/hep.26641. Epub 2013 Oct 11.

    PubMed 23907700

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TMC435, Ribavirin (R) and PegIFNα-2a (P) in people with Hepatitis C, run by Tibotec Pharmaceuticals, Ireland at 71 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 71 sites in United States, Germany, France, Australia, Belgium and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jun 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72) (time frame: Week 72). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00882908, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jun 2014.

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