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 ]

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
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Time Frame 72 weeks
Additional Description No text entered.

Reporting Groups
  Description
T12/PR48 - TVR/PBO TREATMENT 12 weeks of 750 mg telaprevir q8hr followed by 4 weeks of Placebo in combination with 48 weeks of Peg-IFN-alfa-2a and RBV at standard doses - TE AEs during the telaprevir/placebo treatment phase
T12(DS)/PR48 - TVR/PBO TREATMENT 4 weeks of Placebo followed by 12 weeks of 750 mg telaprevir q8hr in combination with 48 weeks of Peg-IFN-alfa-2a and RBV at standard doses - TE AEs during the telaprevir/placebo treatment phase
Pbo/PR48 - TVR/PBO TREATMENT 48 weeks of Peg-IFN-alfa-2a and RBV at standard doses - TE AEs during the telaprevir/placebo treatment phase
T12/PR48 - OVERALL TREATMENT 12 weeks of 750 mg telaprevir q8hr followed by 4 weeks of Placebo in combination with 48 weeks of Peg-IFN-alfa-2a and RBV at standard doses - TE AES during the overall treatment phase
T12(DS)/PR48 - OVERALL TREATMENT 4 weeks of Placebo followed by 12 weeks of 750 mg telaprevir q8hr in combination with 48 weeks of Peg-IFN-alfa-2a and RBV at standard doses - TE AES during the overall treatment phase
Pbo/PR48 - OVERALL TREATMENT 48 weeks of Peg-IFN-alfa-2a and RBV at standard doses - TE AEs during the overall treatment phase

Serious Adverse Events
    T12/PR48 - TVR/PBO TREATMENT     T12(DS)/PR48 - TVR/PBO TREATMENT     Pbo/PR48 - TVR/PBO TREATMENT     T12/PR48 - OVERALL TREATMENT     T12(DS)/PR48 - OVERALL TREATMENT     Pbo/PR48 - OVERALL TREATMENT  
Total, serious adverse events              
# participants affected / at risk     18/266 (6.77%)     17/264 (6.44%)     4/132 (3.03%)     33/266 (12.41%)     32/264 (12.12%)     7/132 (5.30%)  
Blood and lymphatic system disorders              
Anaemia † 1            
# participants affected / at risk     4/266 (1.50%)     5/264 (1.89%)     1/132 (0.76%)     6/266 (2.26%)     7/264 (2.65%)     1/132 (0.76%)  
Febrile neutropenia † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Pancytopenia † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     1/264 (0.38%)     0/132 (0.00%)  
Thrombocytopenia † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Cardiac disorders              
Acute myocardial infarction † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     3/266 (1.13%)     0/264 (0.00%)     0/132 (0.00%)  
Atrial fibrillation † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     2/264 (0.76%)     1/132 (0.76%)  
Cardiac valve disease † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Myocardial infarction † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Supraventricular tachycardia † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Ear and labyrinth disorders              
Sudden hearing loss † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Endocrine disorders              
Basedow's disease † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Eye disorders              
Retinal detachment † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Gastrointestinal disorders              
Abdominal pain † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     1/132 (0.76%)     0/266 (0.00%)     1/264 (0.38%)     1/132 (0.76%)  
Anal fissure † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Caecitis † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Colitis † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     0/264 (0.00%)     1/132 (0.76%)  
Gastrointestinal haemorrhage † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Pancreatitis † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Pancreatitis acute † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     1/264 (0.38%)     0/132 (0.00%)  
General disorders              
General physical health deterioration † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Pyrexia † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Infections and infestations              
Appendicitis † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Bronchitis † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     2/266 (0.75%)     0/264 (0.00%)     0/132 (0.00%)  
Erysipelas † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Folliculitis † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Helicobacter gastritis † 1            
# participants affected / at risk     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Pneumonia † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     1/132 (0.76%)  
Post procedural infection † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Pyelonephritis † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     1/132 (0.76%)     0/266 (0.00%)     0/264 (0.00%)     1/132 (0.76%)  
Rectal abscess † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Sepsis † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     2/264 (0.76%)     0/132 (0.00%)  
Sinusitis † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Tooth abscess † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Urinary tract infection † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     1/264 (0.38%)     0/132 (0.00%)  
Injury, poisoning and procedural complications              
Injection site reaction † 1            
# participants affected / at risk     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Animal scratch † 1            
# participants affected / at risk     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Ankle fracture † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Femoral neck fracture † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Multiple drug overdose † 1            
# participants affected / at risk     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Investigations              
Blood corticotrophin decreased † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Weight decreased † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Metabolism and nutrition disorders              
Anorexia † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Diabetes mellitus † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)              
Bronchial carcinoma † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Gastric cancer † 1            
# participants affected / at risk     0/266 (0.00%)     2/264 (0.76%)     0/132 (0.00%)     0/266 (0.00%)     2/264 (0.76%)     0/132 (0.00%)  
Hepatic neoplasm malignant † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     2/266 (0.75%)     0/264 (0.00%)     0/132 (0.00%)  
Histiocytosis haematophagic † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Lung neoplasm malignant † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Nervous system disorders              
Cerebral thrombosis † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     0/264 (0.00%)     1/132 (0.76%)  
Coma † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     1/132 (0.76%)     0/266 (0.00%)     0/264 (0.00%)     1/132 (0.76%)  
Lethargy † 1            
# participants affected / at risk     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Subarachnoid haemorrhage † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Syncope † 1            
# participants affected / at risk     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)     1/266 (0.38%)     1/264 (0.38%)     0/132 (0.00%)  
Psychiatric disorders              
Delirium † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Depression † 1            
# participants affected / at risk     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Insomnia † 1            
# participants affected / at risk     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Substance abuse † 1            
# participants affected / at risk     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Renal and urinary disorders              
Renal cyst † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Renal failure † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Urinary bladder polyp † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Reproductive system and breast disorders              
Prostatitis † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Respiratory, thoracic and mediastinal disorders              
Pulmonary embolism † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Skin and subcutaneous tissue disorders              
Dermatitis † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Eczema † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Erythema multiforme † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Pruritus † 1            
# participants affected / at risk     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Pustular psoriasis † 1            
# participants affected / at risk     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Rash † 1            
# participants affected / at risk     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Toxic skin eruption † 1            
# participants affected / at risk     0/266 (0.00%)     2/264 (0.76%)     0/132 (0.00%)     0/266 (0.00%)     2/264 (0.76%)     0/132 (0.00%)  
Vascular disorders              
Orthostatic hypotension † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     0/266 (0.00%)     1/264 (0.38%)     0/132 (0.00%)  
Peripheral artery aneurysm † 1            
# participants affected / at risk     0/266 (0.00%)     0/264 (0.00%)     0/132 (0.00%)     1/266 (0.38%)     0/264 (0.00%)     0/132 (0.00%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 11.0




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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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