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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/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) - The table below shows the percentage of participants in the overall population with an SVR24, defined as having plasma levels of Hepatitis C Virus ribonucleic acid less than 25 IU/mL undetectable at the EOT and 24 weeks after the EOT.
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 - The table below shows the percentage of participants in each treatment group who achieved a greater than 2 log10 drop in plasma levels of HCV RNA at selected 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 - The table below shows the percentage of participants in each treatment who achieved plasma HCV RNA levels of <25 IU/mL undetectable at selected time points during treatment and follow-up and at the end of treatment (EOT).
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 - The table below shows the percentage of participants in each treatment group who achieved plasma HCV RNA levels below the limit of quantification defined as less than 25 IU/mL (detectable or undetectable) at selected time points during treatment, follow-up, and at the end of treatment (EOT).
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) - The table below shows the percentage of participants in each treatment group who achieved a RVR, defined as having an undetectable plasma Hepatitis C virus ribonucleic acid level after receiving 4 weeks of treatment.
Timepoint [4] 0 0
Week 4
Secondary outcome [5] 0 0
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 greater than or equal to 2 log10 reduction in plasma Hepatitis C virus ribonucleic acid from baseline at Week 12.
Timepoint [5] 0 0
Week 12
Secondary outcome [6] 0 0
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 levels of Hepatitis C virus ribonucleic acid at Week 12.
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) - The table below shows the percentage of participants in the overall population who achieved undetectable plasma Hepatitis C virus ribonucleic acid levels at the end of treatment (EOT) and 12 Weeks after the planned EOT.
Timepoint [7] 0 0
Week 60
Secondary outcome [8] 0 0
The Percentage of Participants With Viral Breakthrough - The table below shows the percentage of participants in the overall population in each treatment group during the treatment period who experienced viral breakthrough, defined as a confirmed increase of greater than 1 log10 IU/mL in Hepatitis C virus (HCV) ribonucleic acid (RNA) from the lowest level reached or a confirmed HCV RNA of > 100 IU/mL in participants whose HCV RNA had previously been below the lower limit of quantification (i.e., less than 25 IU/mL detectable or undetectable).
Timepoint [8] 0 0
EOT (up to Week 48)
Secondary outcome [9] 0 0
The Percentage of Participants With Viral Relapse - The table below shows the percentage of participants in the overall population who had viral relapse, defined as confirmed detectable Hepatitis C virus (HCV) ribonucleic acid (RNA) during the follow-up period in participants with HCV RNA less than 25 IU/mL undetectable at end of treatment.
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) - The table below shows the number of participants with abnormal ALT levels at Baseline who achieved the normal ALT levels at the EOT (up to Week 48).
Timepoint [10] 0 0
EOT (up to Week 48)
Secondary outcome [11] 0 0
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 TMC435 for participants in each of the 6 TMC435 treatment groups.
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 - The table below shows the median (range) AUC24h values for TMC435 for participants in each TMC435 treatment group.
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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Country [25] 0 0
France
State/province [25] 0 0
Lyon
Country [26] 0 0
France
State/province [26] 0 0
Nice
Country [27] 0 0
France
State/province [27] 0 0
Paris Cedex 12
Country [28] 0 0
France
State/province [28] 0 0
Paris
Country [29] 0 0
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
Country [52] 0 0
Poland
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Bydgoszcz
Country [53] 0 0
Poland
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Czeladz
Country [54] 0 0
Poland
State/province [54] 0 0
Kielce
Country [55] 0 0
Poland
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Warszawa
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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
State/province [60] 0 0
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/show/NCT00980330
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
Other publications