Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00882908




Registration number
NCT00882908
Ethics application status
Date submitted
16/04/2009
Date registered
17/04/2009
Date last updated
16/06/2014

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
TMC435-TiDP16-C205
Secondary ID [2] 0 0
CR015799
Universal Trial Number (UTN)
Trial acronym
PILLAR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - TMC435
Treatment: Drugs - Ribavirin (R)
Treatment: Drugs - PegIFNa-2a (P)
Treatment: Drugs - Placebo

Experimental: TMC435 75 mg 12 Wks + PR 24/48 - Participants will receive TMC435 75 mg once daily with PegIFNa-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.

Experimental: TMC435 75 mg 24 Wks + PR 24/48 - Participants will receive TMC435 75 mg once daily with PegIFNa-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.

Experimental: TMC435 150 mg 12 Wks + PR 24/48 - Participants will receive TMC435 150 mg once daily with PegIFNa-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.

Experimental: TMC435 150 mg 24 Wks + PR 24/48 - Participants will receive TMC435 150 mg once daily with PegIFNa-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.

Placebo Comparator: Placebo 24 Wks + PR48 - Participants will receive Placebo once daily with PegIFNa-2a (P) and ribavirin (R) for 24 weeks followed by PR until Week 48.


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

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

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

Treatment: Drugs: Placebo
Placebo capsules identical in appearance to TMC435 capsule will be administered orally, once daily, for 48 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The Percentage of Participants Achieving a Sustained Virologic Response at Week 72 (SVRW72)
Timepoint [1] 0 0
Week 72
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Weeks 2, 4, 8, 12, 24, 36, 48, 60, 72, and at EOT (up to Week 24 or 48)
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
Baseline (Day 1) and Weeks, 2, 4, 8, and 12
Secondary outcome [4] 0 0
The Percentage of Participants Who Achieved a Sustained Virologic Response 24 Weeks After the Planned End of Treatment (SVR24)
Timepoint [4] 0 0
Week 48 or 72
Secondary outcome [5] 0 0
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
Timepoint [5] 0 0
Week 4
Secondary outcome [6] 0 0
The Percentage of Participants Achieving an Early Virologic Response (EVR)
Timepoint [6] 0 0
Baseline (Day 1) and Week 12
Secondary outcome [7] 0 0
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
Timepoint [7] 0 0
Week 12
Secondary outcome [8] 0 0
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Timepoint [8] 0 0
Up to Week 36 or 52
Secondary outcome [9] 0 0
Number of Participants With Viral Breakthrough
Timepoint [9] 0 0
Week 24 or 48
Secondary outcome [10] 0 0
The Number of Participants With Viral Relapse
Timepoint [10] 0 0
Up to Week 72
Secondary outcome [11] 0 0
The Number of Participants With Abnormal Alanine Aminotransferase (ALT) Levels at Baseline Who Achieved Normalized ALT Levels at the End of Treatment (EOT)
Timepoint [11] 0 0
Baseline (Day 1) up to Week 24 or 48
Secondary outcome [12] 0 0
Plasma Concentrations of TMC435
Timepoint [12] 0 0
Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24
Secondary outcome [13] 0 0
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
Timepoint [13] 0 0
Two random blood samples taken at least 2 hours apart at Weeks 2, 4, 8, 12, 16, and 24

Eligibility
Key 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
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2011
Sample size
Target
Accrual to date
Final
386
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Concord
Recruitment hospital [2] 0 0
- Darlinghurst
Recruitment hospital [3] 0 0
- Fitzroy
Recruitment hospital [4] 0 0
- Melbourne
Recruitment hospital [5] 0 0
- Sydney
Recruitment hospital [6] 0 0
- Woolloongabba N/A
Recruitment postcode(s) [1] 0 0
- Concord
Recruitment postcode(s) [2] 0 0
- Darlinghurst
Recruitment postcode(s) [3] 0 0
- Fitzroy
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment postcode(s) [5] 0 0
- Sydney
Recruitment postcode(s) [6] 0 0
- Woolloongabba N/A
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
Austria
State/province [11] 0 0
Wien
Country [12] 0 0
Belgium
State/province [12] 0 0
Brugge
Country [13] 0 0
Belgium
State/province [13] 0 0
Brussels
Country [14] 0 0
Belgium
State/province [14] 0 0
Bruxelles
Country [15] 0 0
Belgium
State/province [15] 0 0
Edegem
Country [16] 0 0
Belgium
State/province [16] 0 0
Gent
Country [17] 0 0
Belgium
State/province [17] 0 0
Leuven
Country [18] 0 0
Belgium
State/province [18] 0 0
Roeselare
Country [19] 0 0
Canada
State/province [19] 0 0
Alberta
Country [20] 0 0
Canada
State/province [20] 0 0
Ontario
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
Denmark
State/province [22] 0 0
Aarhus
Country [23] 0 0
Denmark
State/province [23] 0 0
Copenhagen
Country [24] 0 0
Denmark
State/province [24] 0 0
Hvidovre N/A
Country [25] 0 0
Denmark
State/province [25] 0 0
Kolding
Country [26] 0 0
Denmark
State/province [26] 0 0
Odense N/A
Country [27] 0 0
France
State/province [27] 0 0
Clichy
Country [28] 0 0
France
State/province [28] 0 0
Creteil N/A
Country [29] 0 0
France
State/province [29] 0 0
Grenoble
Country [30] 0 0
France
State/province [30] 0 0
Lyon
Country [31] 0 0
France
State/province [31] 0 0
Nice
Country [32] 0 0
France
State/province [32] 0 0
Paris
Country [33] 0 0
France
State/province [33] 0 0
Vandoeuvre Les Nancy
Country [34] 0 0
Germany
State/province [34] 0 0
Berlin
Country [35] 0 0
Germany
State/province [35] 0 0
Düsseldorf
Country [36] 0 0
Germany
State/province [36] 0 0
Frankfurt A. M.
Country [37] 0 0
Germany
State/province [37] 0 0
Freiburg
Country [38] 0 0
Germany
State/province [38] 0 0
Hamburg
Country [39] 0 0
Germany
State/province [39] 0 0
Hannover
Country [40] 0 0
Germany
State/province [40] 0 0
Köln
Country [41] 0 0
Germany
State/province [41] 0 0
Stuttgart
Country [42] 0 0
Germany
State/province [42] 0 0
Würzburg
Country [43] 0 0
New Zealand
State/province [43] 0 0
Auckland
Country [44] 0 0
New Zealand
State/province [44] 0 0
Christchurch
Country [45] 0 0
New Zealand
State/province [45] 0 0
Hamilton
Country [46] 0 0
Norway
State/province [46] 0 0
Bergen
Country [47] 0 0
Norway
State/province [47] 0 0
Nordbyhagen
Country [48] 0 0
Norway
State/province [48] 0 0
Oslo
Country [49] 0 0
Norway
State/province [49] 0 0
Tromsø
Country [50] 0 0
Poland
State/province [50] 0 0
Bialystok
Country [51] 0 0
Poland
State/province [51] 0 0
Bydgoszcz
Country [52] 0 0
Poland
State/province [52] 0 0
Czeladz
Country [53] 0 0
Poland
State/province [53] 0 0
Kielce
Country [54] 0 0
Poland
State/province [54] 0 0
Lodz
Country [55] 0 0
Poland
State/province [55] 0 0
Warschau
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Moscow
Country [57] 0 0
Russian Federation
State/province [57] 0 0
Nizhny Novgorod
Country [58] 0 0
Russian Federation
State/province [58] 0 0
Saint-Petersburg
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Samara
Country [60] 0 0
Russian Federation
State/province [60] 0 0
Smolensk
Country [61] 0 0
Russian Federation
State/province [61] 0 0
St Petersburg
Country [62] 0 0
Spain
State/province [62] 0 0
Barcelona
Country [63] 0 0
Spain
State/province [63] 0 0
Madrid
Country [64] 0 0
Spain
State/province [64] 0 0
Sevilla N/A
Country [65] 0 0
Spain
State/province [65] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Tibotec Pharmaceuticals, Ireland
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the efficacy of 4 different regimens of TMC435 in
combination with peginterferon alfa-2a (PegIFNa-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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00882908
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Tibotec Pharmaceuticals, Ireland Clinical Trial
Address 0 0
Tibotec Pharmaceuticals, Ireland
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00882908