A Safety and Effectiveness Study of Telaprevir in Chronic, Genotype 1, Hepatitis C Patients That Failed Previous Standard Treatment

This study has been completed.
Sponsor:
Collaborator:
Tibotec Pharmaceutical Limited
Information provided by (Responsible Party):
Tibotec BVBA
ClinicalTrials.gov Identifier:
NCT00703118
First received: June 19, 2008
Last updated: December 5, 2013
Last verified: December 2013
Results First Received: July 18, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Hepatitis C, Chronic
Interventions: Drug: Telaprevir
Drug: Peg-IFN-alfa-2a
Drug: Ribavirin
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study was conducted at 105 sites in 17 countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Switzerland, Germany, Spain, France, United Kingdom, Israel, Italy, Netherlands, Poland, Sweden, and the United States.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
662 participants were treated (266 participants in the T12/PR48 group, 264 participants in the T12(DS)/PR48 group, and 132 participants in the Pbo/PR48 group) in this study.

Reporting Groups
  Description
T12/PR48 12 weeks of 750 mg telaprevir eight hourly followed by 4 weeks of Placebo in combination with 48 weeks of Peg-IFN-alfa-2a and ribavirin at standard doses
T12(DS)/PR48 4 weeks of Placebo followed by 12 weeks of 750 mg telaprevir eight hourly in combination with 48 weeks of Peg-IFN-alfa-2a and ribavirin at standard doses
Pbo/PR48 48 weeks of Peg-IFN-alfa-2a and ribavirin at standard doses

Participant Flow:   Overall Study
    T12/PR48     T12(DS)/PR48     Pbo/PR48  
STARTED     266     264     132  
COMPLETED     245     248     110  
NOT COMPLETED     21     16     22  
Adverse Event                 1                 2                 2  
Subject Ineligible To Continue The Trial                 6                 3                 2  
Lost to Follow-up                 6                 4                 4  
Withdrawal by Subject                 8                 7                 13  
Not specified                 0                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
T12/PR48 12 weeks of 750 mg telaprevir eight hourly followed by 4 weeks of Placebo in combination with 48 weeks of Peg-IFN-alfa-2a and ribavirin at standard doses
T12(DS)/PR48 4 weeks of Placebo followed by 12 weeks of 750 mg telaprevir eight hourly in combination with 48 weeks of Peg-IFN-alfa-2a and ribavirin at standard doses
Pbo/PR48 48 weeks of Peg-IFN-alfa-2a and ribavirin at standard doses
Total Total of all reporting groups

Baseline Measures
    T12/PR48     T12(DS)/PR48     Pbo/PR48     Total  
Number of Participants  
[units: participants]
  266     264     132     662  
Age  
[units: years]
Mean ± Standard Deviation
  50.7  ± 8.51     51  ± 8.24     49.9  ± 9.74     50.6  ± 8.66  
Gender  
[units: participants]
       
Female     83     75     44     202  
Male     183     189     88     460  
Race/Ethnicity, Customized  
[units: Participants]
       
Asian     6     2     3     11  
Black or African American     11     8     11     30  
White     246     252     117     615  
Other     3     2     1     6  
AgeCategoricalOther  
[units: participants]
       
>= 45 years     64     55     40     159  
Between 45 and 65 years     197     201     85     483  
>= 65 years     5     8     7     20  



  Outcome Measures
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1.  Primary:   Number of Participants With Sustained Virologic Response (SVR) 24 Weeks After the Last Planned Dose of Study Medication - SVR24 Planned   [ Time Frame: Week 72 ]
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Measure Type Primary
Measure Title Number of Participants With Sustained Virologic Response (SVR) 24 Weeks After the Last Planned Dose of Study Medication - SVR24 Planned
Measure Description SVR24 planned is defined as having undetectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) levels 24 weeks after the last planned dose of study medication.
Time Frame Week 72  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full Analysis Set: All randomized participants who received at least one dose of study medication.

Reporting Groups
  Description
T12/PR48 12 weeks of 750 mg telaprevir eight hourly followed by 4 weeks of Placebo in combination with 48 weeks of Peg-IFN-alfa-2a and ribavirin at standard doses
T12(DS)/PR48 4 weeks of Placebo followed by 12 weeks of 750 mg telaprevir eight hourly in combination with 48 weeks of Peg-IFN-alfa-2a and ribavirin at standard doses
Pbo/PR48 48 weeks of Peg-IFN-alfa-2a and ribavirin at standard doses

Measured Values
    T12/PR48     T12(DS)/PR48     Pbo/PR48  
Number of Participants Analyzed  
[units: participants]
  266     264     132  
Number of Participants With Sustained Virologic Response (SVR) 24 Weeks After the Last Planned Dose of Study Medication - SVR24 Planned  
[units: Participants]
  171     175     22  


Statistical Analysis 1 for Number of Participants With Sustained Virologic Response (SVR) 24 Weeks After the Last Planned Dose of Study Medication - SVR24 Planned
Groups [1] T12/PR48 vs. Pbo/PR48
Method [2] Regression, Logistic
P Value [3] <0.001
Difference in percentage of response [4] 46.8
95% Confidence Interval ( 36.8 to 56.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Null hypothesis: Assuming a 55% response rate in the groups receiving Treatment T12/PR48, a 29% response rate in the group receiving Treatment Pbo/PR48, a 2-sided continuity corrected Chi-squared test, with an overall significance level of 5% and a 2:2:1 randomization, a sample size of 140 patients receiving Treatment T12/PR48 and 70 patients in receiving Treatment Pbo/PR48 provided a power of approximately 90% to demonstrate a statistically significant difference.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Included: treatment, type of prior response (relapser, partial responder, null-responder) and their interaction, and baseline HCV RNA as a covariate
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Overall significance level was set at 5% (two-sided). Adjustment of significance level for multiple comparisons was carried out using the Hochberg procedure
[4] Other relevant estimation information:
  Difference in percentage of response was estimated through the logistic regression model.

Statistical Analysis 2 for Number of Participants With Sustained Virologic Response (SVR) 24 Weeks After the Last Planned Dose of Study Medication - SVR24 Planned
Groups [1] T12(DS)/PR48 vs. Pbo/PR48
Method [2] Regression, Logistic
P Value [3] <0.001
Difference in percentage of response [4] 49.8
95% Confidence Interval ( 39.9 to 59.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Null hypothesis: Assuming a 55% response rate in the groups receiving Treatment T12/PR48 or T12(DS)/PR48, a 29% response rate in the group receiving Treatment Pbo/PR48, a 2-sided continuity corrected Chi-squared test, with an overall significance level of 5% and a 2:2:1 randomization, a sample size of 140 patients receiving Treatment T12(DS)/PR48 and 70 patients in receiving Treatment Pbo/PR48 provided a power of approximately 90% to demonstrate a statistically significant difference.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Included: treatment, type of prior response (relapser, partial responder, null-responder) and their interaction, and baseline HCV RNA as a covariate
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Overall significance level was set at 5% (two-sided). Adjustment of significance level for multiple comparisons was carried out using the Hochberg procedure
[4] Other relevant estimation information:
  Difference in percentage of response was estimated through the logistic regression model.



2.  Secondary:   Number of Participants Acheiving Rapid Virologic Response (RVR) at Week 4   [ Time Frame: Week 4 ]

3.  Secondary:   Number of Participants Acheiving Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Week 48 (End of Treatment)   [ Time Frame: Week 48 ]

4.  Secondary:   Number of Participants With Sustained Virologic Response (SVR) 12 Weeks After the Last Planned Dose of Study Medication - SVR12 Planned   [ Time Frame: Week 60 ]

5.  Secondary:   Number of Participants Who Meet the Telaprevir Stopping Rule at Week 4, Week 6, or Week 8   [ Time Frame: Week 4, Week 6, or Week 8 ]

6.  Secondary:   Number of Participants Who Have Viral Relapse During Entire Follow-up Period (up to Week 72)   [ Time Frame: Up to Week 72 ]

7.  Secondary:   Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4   [ Time Frame: Baseline (Day 1) to Week 4 ]

8.  Secondary:   Number of Participants Acheiving Extended Rapid Virologic Response at Week 4 and Week 12   [ Time Frame: Week 4 and Week 12 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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