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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00980330




Registration number
NCT00980330
Ethics application status
Date submitted
10/09/2009
Date registered
21/09/2009
Date last updated
9/06/2014

Titles & IDs
Public title
A Safety and Effectiveness Study of TMC435 in Chronic, Genotype 1, Hepatitis C Patients Who Failed to Previous Standard 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 PegIFNa-2a and Ribavirin in HCV Genotype 1 Infected Subjects Who Failed Previous Standard Therapy
Secondary ID [1] 0 0
TMC435-TiDP16-C206
Secondary ID [2] 0 0
CR016063
Universal Trial Number (UTN)
Trial acronym
ASPIRE
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 - Placebo
Treatment: Drugs - Peg-IFN-alfa-2a (P)
Treatment: Drugs - Ribavirin (R)

Experimental: TMC435 100 mg 12 Wks + PR48 - Participants will receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo with PR for 36 weeks.

Experimental: TMC435 100 mg 24 Wks + PR48 - Participants willl receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed by Placebo with PR for 24 weeks.

Experimental: TMC435 100 mg 48 Wks + PR48 - Participants will receive TMC435 100 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.

Experimental: TMC435 150 mg 12 Wks + PR48 - Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 12 weeks followed by Placebo and PR for 36 weeks.

Experimental: TMC435 150 mg 24 Wks + PR48 - Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 24 weeks followed Placebo and PR for 24 weeks.

Experimental: TMC435 150 mg 48 Wks + PR48 - Participants will receive TMC435 150 mg once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.

Placebo comparator: Placebo 48 Wks + PR48 - Participants will receive Placebo once daily with Peg-IFN-alfa-2a (P) once weekly and ribavirin (R) twice daily for 48 weeks.


Treatment: Drugs: TMC435
One TMC435 100-mg capsule or two 75-mg capsules orally (by mouth) once daily for 12, 24, or 48 weeks.

Treatment: Drugs: Placebo
One or 2 capsules of placebo identical in appearance to TMC435 taken orally once daily for 24, 36, or 48 weeks.

Treatment: Drugs: Peg-IFN-alfa-2a (P)
180 micrograms taken as one 0.5 mL subcutaneous injection once weekly for 48 weeks.

Treatment: Drugs: Ribavirin (R)
1000 or 1200 mg/day (5 or 6 tablets) taken orally as a twice daily regimen taken 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 the End of Treatment (EOT) and 24 Weeks After the EOT (SVR24)
Timepoint [1] 0 0
Week 72
Secondary outcome [1] 0 0
The Percentage of Participants With a Greater Than 2 log10 Drop in Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Time Points During Treatment
Timepoint [1] 0 0
Weeks, 2, 4, 8, and 12
Secondary outcome [2] 0 0
The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Undetectable During Treatment and Follow-up
Timepoint [2] 0 0
Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72 and EOT (up to Week 48)
Secondary outcome [3] 0 0
The Percentage of Participants Achieving Plasma Levels of Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) <25 IU/mL Detectable or Undetectable During Treatment and Follow-up
Timepoint [3] 0 0
Weeks, 2, 4, 8, 12, 24, 36, 48, 60, 72, and EOT (up to Week 48)
Secondary outcome [4] 0 0
The Percentage of Participants Achieving a Rapid Virologic Response (RVR)
Timepoint [4] 0 0
Week 4
Secondary outcome [5] 0 0
The Percentage of Participants Achieving an Early Virologic Response (EVR)
Timepoint [5] 0 0
Week 12
Secondary outcome [6] 0 0
The Percentage of Participants Achieving a Complete Early Virologic Response (cEVR)
Timepoint [6] 0 0
Week 12
Secondary outcome [7] 0 0
The Percentage of Participants Achieving a Sustained Virologic Response 12 Weeks After the Planned End of Treatment (SVR12)
Timepoint [7] 0 0
Week 60
Secondary outcome [8] 0 0
The Percentage of Participants With Viral Breakthrough
Timepoint [8] 0 0
EOT (up to Week 48)
Secondary outcome [9] 0 0
The Percentage of Participants With Viral Relapse
Timepoint [9] 0 0
Up to Week 72
Secondary outcome [10] 0 0
The Number of Participants Who Achieved Normalized Alanine Aminotransferase (ALT) Levels at the End of Treatment (EOT)
Timepoint [10] 0 0
EOT (up to Week 48)
Secondary outcome [11] 0 0
Plasma Concentrations of TMC435
Timepoint [11] 0 0
0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48
Secondary outcome [12] 0 0
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24h) for TMC435
Timepoint [12] 0 0
0 (predose, baseline) and 4, 8, 12, and 24 hours post-dose at Weeks 2, 4, 8, 12, 16, 24, and 48

Eligibility
Key inclusion criteria
* Must have chronic hepatitis C infection as evidenced by liver biopsy, anti-hepatitis C virus (HCV) and HCV RNA positive
* Must have chronic hepatitis C infection (genotype 1) with HCV RNA level greater than10000 IU/mL
* Patient must have failed at least 1 prior course of peg interferon (Peg-IFN-alfa-2a)/ribavirin (RBV) therapy (standard treatment)
* Must be willing to use 2 effective methods of birth control for up to 7 months after last dose of study medication
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has an evidence of decompensated liver disease
* Co-infection with any other Hepatitis C virus genotype or co-infection with the human immunodeficiency virus (HIV)
* Has a medical condition which is a contraindication to Peg-INF or RBV therapy
* Have had 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
1/10/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2011
Sample size
Target
Accrual to date
Final
463
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
- New Lambton Heights
Recruitment hospital [6] 0 0
- Parkville
Recruitment hospital [7] 0 0
- Sydney
Recruitment hospital [8] 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
- New Lambton Heights
Recruitment postcode(s) [6] 0 0
- Parkville
Recruitment postcode(s) [7] 0 0
- Sydney
Recruitment postcode(s) [8] 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
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Mississippi
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
Austria
State/province [12] 0 0
Wien
Country [13] 0 0
Belgium
State/province [13] 0 0
Brugge
Country [14] 0 0
Belgium
State/province [14] 0 0
Brussels
Country [15] 0 0
Belgium
State/province [15] 0 0
Bruxelles
Country [16] 0 0
Belgium
State/province [16] 0 0
Edegem
Country [17] 0 0
Belgium
State/province [17] 0 0
Gent
Country [18] 0 0
Belgium
State/province [18] 0 0
Leuven
Country [19] 0 0
Belgium
State/province [19] 0 0
Roeselare
Country [20] 0 0
Canada
State/province [20] 0 0
Alberta
Country [21] 0 0
Canada
State/province [21] 0 0
Ontario
Country [22] 0 0
Canada
State/province [22] 0 0
Quebec
Country [23] 0 0
France
State/province [23] 0 0
Creteil N/A
Country [24] 0 0
France
State/province [24] 0 0
Grenoble
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France
State/province [25] 0 0
Lyon
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France
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Nice
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France
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Paris Cedex 12
Country [28] 0 0
France
State/province [28] 0 0
Paris
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France
State/province [29] 0 0
Vandoeuvre Les Nancy
Country [30] 0 0
Germany
State/province [30] 0 0
Berlin
Country [31] 0 0
Germany
State/province [31] 0 0
Düsseldorf
Country [32] 0 0
Germany
State/province [32] 0 0
Frankfurt A. M.
Country [33] 0 0
Germany
State/province [33] 0 0
Freiburg
Country [34] 0 0
Germany
State/province [34] 0 0
Hannover
Country [35] 0 0
Germany
State/province [35] 0 0
Köln
Country [36] 0 0
Germany
State/province [36] 0 0
Stuttgart
Country [37] 0 0
Germany
State/province [37] 0 0
Würzburg
Country [38] 0 0
Israel
State/province [38] 0 0
Haifa
Country [39] 0 0
Israel
State/province [39] 0 0
Jerusalem
Country [40] 0 0
Israel
State/province [40] 0 0
Nazareth
Country [41] 0 0
Israel
State/province [41] 0 0
Petah Tiqva
Country [42] 0 0
Israel
State/province [42] 0 0
Ramat-Gan
Country [43] 0 0
Israel
State/province [43] 0 0
Tel-Aviv
Country [44] 0 0
Israel
State/province [44] 0 0
Zefat
Country [45] 0 0
New Zealand
State/province [45] 0 0
Auckland
Country [46] 0 0
New Zealand
State/province [46] 0 0
Christchurch
Country [47] 0 0
New Zealand
State/province [47] 0 0
Hamilton
Country [48] 0 0
Norway
State/province [48] 0 0
Nordbyhagen
Country [49] 0 0
Norway
State/province [49] 0 0
Oslo
Country [50] 0 0
Norway
State/province [50] 0 0
Tromsø
Country [51] 0 0
Poland
State/province [51] 0 0
Bialystok
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Poland
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Bydgoszcz
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Poland
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Czeladz
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Poland
State/province [54] 0 0
Kielce
Country [55] 0 0
Poland
State/province [55] 0 0
Warszawa
Country [56] 0 0
Portugal
State/province [56] 0 0
Coimbra
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Portugal
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Lisboa
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Portugal
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Porto
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Russian Federation
State/province [59] 0 0
Moscow
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Russian Federation
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Nizhny Novgorod
Country [61] 0 0
Russian Federation
State/province [61] 0 0
Saint-Petersburg
Country [62] 0 0
Russian Federation
State/province [62] 0 0
Samara
Country [63] 0 0
Russian Federation
State/province [63] 0 0
Smolensk
Country [64] 0 0
Russian Federation
State/province [64] 0 0
St Petersburg
Country [65] 0 0
United Kingdom
State/province [65] 0 0
London
Country [66] 0 0
United Kingdom
State/province [66] 0 0
Plymouth

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 determine the efficacy, safety and tolerability of different regimens of TMC435 with standard treatment compared to standard treatment alone in participants with chronic, genotype 1, hepatitis C virus (HCV) infection who has failed previous treatment with pegylated interferon (Peg-INF-alfa-2a) and ribavirin (RBV).
Trial website
https://clinicaltrials.gov/study/NCT00980330
Trial related presentations / 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.
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.
Zeuzem S, Berg T, Gane E, Ferenci P, Foster GR, Fried MW, Hezode C, Hirschfield GM, Jacobson I, Nikitin I, Pockros PJ, Poordad F, Scott J, Lenz O, Peeters M, Sekar V, De Smedt G, Sinha R, Beumont-Mauviel M. Simeprevir increases rate of sustained virologic response among treatment-experienced patients with HCV genotype-1 infection: a phase IIb trial. Gastroenterology. 2014 Feb;146(2):430-41.e6. doi: 10.1053/j.gastro.2013.10.058. Epub 2013 Nov 1.
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/study/NCT00980330