A Phase 3 Study of Telaprevir in Combination With Pegasys® and Copegus® in Treatment-Naive Subjects With Genotype 1 Hepatitis C Virus (HCV)

This study has been completed.
Sponsor:
Collaborator:
Tibotec Pharmaceutical Limited
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT00627926
First received: February 22, 2008
Last updated: July 16, 2014
Last verified: July 2014
Results First Received: June 22, 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
Interventions: Biological: Pegylated Interferon Alfa 2a
Drug: Telaprevir
Drug: Ribavirin
Other: 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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 1095 subjects were enrolled, of which 7 subjects discontinued the study prior to study drug administration. A total of 1088 subjects started treatment.

Reporting Groups
  Description
PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week Placebo (PBO) matched to telaprevir 750 mg tablet thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) tablet orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks.
Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week Telaprevir 750 mg tablet thrice daily for 8 weeks, then PBO matched to Telaprevir 750 mg tablet thrice daily for 4 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 to 48 weeks depending on individual response to telaprevir treatment.
Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week Telaprevir 750 mg tablet thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 to 48 weeks depending on individual response to telaprevir treatment.

Participant Flow:   Overall Study
    PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week     Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week     Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week  
STARTED     361     364     363  
COMPLETED     202     260     268  
NOT COMPLETED     159     104     95  
Adverse Event                 26                 37                 36  
Death                 1                 0                 0  
Lost to Follow-up                 4                 3                 4  
Withdrawal by Subject                 2                 1                 0  
Lack of Efficacy                 118                 40                 38  
Noncompliance/unspecified                 8                 23                 17  



  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.
The full analysis (FA) set included all randomized subjects who received at least 1 dose of any study drug.

Reporting Groups
  Description
PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week Placebo (PBO) matched to telaprevir 750 mg tablet thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) tablet orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks.
Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week Telaprevir 750 mg tablet thrice daily for 8 weeks, then PBO matched to Telaprevir 750 mg tablet thrice daily for 4 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 to 48 weeks depending on individual response to telaprevir treatment.
Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week Telaprevir 750 mg tablet thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 to 48 weeks depending on individual response to telaprevir treatment.
Total Total of all reporting groups

Baseline Measures
    PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week     Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week     Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week     Total  
Number of Participants  
[units: participants]
  361     364     363     1088  
Age  
[units: participants]
       
<=18 years     1     0     0     1  
Between 18 and 65 years     357     359     353     1069  
>=65 years     3     5     10     18  
Age  
[units: years]
Mean ± Standard Deviation
  46.8  ± 10.0     47.0  ± 10.9     46.5  ± 10.8     46.8  ± 10.6  
Gender  
[units: participants]
       
Female     150     153     149     452  
Male     211     211     214     636  
Region of Enrollment  
[units: participants]
       
North America     214     227     214     655  
Europe     106     100     104     310  
Argentina     8     6     3     17  
Australia     14     14     18     46  
Israel     19     17     24     60  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Subjects Achieving Sustained Viral Response (SVR), Demonstrated by Achieving Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels 24 Weeks After Last Planned Dose of Study Treatment   [ Time Frame: 24 weeks after last planned dose of study treatment (up to Week 72) ]

2.  Secondary:   Number of Subjects With Undetectable HCV RNA at Week 72   [ Time Frame: Week 72 (24 weeks after last dose for subjects with a planned treatment duration of 48 weeks and 48 weeks after last dose for subjects with planned treatment duration of 24 weeks) ]

3.  Secondary:   Number of Subjects Achieving Rapid Viral Response (RVR), Demonstrated by Achieving Undetectable HCV RNA 4 Weeks After Starting Study Treatment   [ Time Frame: Week 4 ]

4.  Secondary:   Number of Subjects Achieving Extended Rapid Viral Response (eRVR), Demonstrated by Achieving Undetectable HCV RNA at Week 4 and at Week 12   [ Time Frame: Week 4 and Week 12 ]

5.  Secondary:   Number of Subjects With Undetectable HCV RNA at Week 12   [ Time Frame: Week 12 ]

6.  Secondary:   Number of Subjects With Undetectable HCV RNA at End of Treatment (EOT)   [ Time Frame: End of treatment (up to Week 48) ]

7.  Secondary:   Number of Subjects With Undetectable HCV RNA 12 Weeks After Last Planned Dose of Study Treatment   [ Time Frame: 12 weeks after last planned dose of study treatment (up to Week 60) ]

8.  Secondary:   Number of Subjects With Undetectable HCV RNA 24 Weeks After Last Actual Dose of Study Treatment   [ Time Frame: 24 weeks after last actual dose of study treatment (up to Week 72) ]

9.  Secondary:   Number of Subjects With Viral Relapse Planned and Viral Relapse Actual   [ Time Frame: After last dose of study drug up to 24 week antiviral follow-up (up to Week 72) ]

10.  Secondary:   Biochemical Response: Number of Subjects With Grade 3 and 4 Shifts From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels   [ Time Frame: Baseline up to Week 48 ]

11.  Secondary:   Noninvasive Markers of Fibrosis: Number of Subjects With Improvement in FibroTest Analysis   [ Time Frame: Baseline through 24 weeks after last planned dose of study treatment (up to Week 72) ]

12.  Secondary:   Fatigue Severity Scale (FSS) Total Score   [ Time Frame: Baseline, Week 4, 12, 24, 36, 48, 72 ]

13.  Secondary:   Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)   [ Time Frame: Baseline up to Week 48 ]


  Serious Adverse Events
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Time Frame AEs and SAEs During Dosing From Baseline to Week 48
Additional Description In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables.

Reporting Groups
  Description
PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week Placebo (PBO) matched to telaprevir 750 mg tablet thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) tablet orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks.
Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week Telaprevir 750 mg tablet thrice daily for 8 weeks, then PBO matched to Telaprevir 750 mg tablet thrice daily for 4 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 to 48 weeks depending on individual response to telaprevir treatment.
Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week Telaprevir 750 mg tablet thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 to 48 weeks depending on individual response to telaprevir treatment.

Serious Adverse Events
    PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week     Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week     Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week  
Total, serious adverse events        
# participants affected / at risk     24/361 (6.65%)     31/364 (8.52%)     33/363 (9.09%)  
Blood and lymphatic system disorders        
anemia † 1      
# participants affected / at risk     4/361 (1.11%)     10/364 (2.75%)     8/363 (2.20%)  
neutropenia † 1      
# participants affected / at risk     1/361 (0.28%)     1/364 (0.27%)     0/363 (0.00%)  
anemia haemolytic † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
leukopenia † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
pancytopenia † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
thrombocytopenia † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
Cardiac disorders        
atrial fibrillation † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     1/363 (0.28%)  
angina pectoris † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
palpitations † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
Congenital, familial and genetic disorders        
urachal abnormality † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
Eye disorders        
retinal exudates † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
retinal haemorrhage † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
vision blurred † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
Gastrointestinal disorders        
abdominal pain † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
anal fistula † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
colitis ischaemic † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
diarrhoea † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
diverticular perforation † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
inguinal hernia † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
internal hernia † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
intestinal ischaemia † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
pancreatitis † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
pancreatitis acute † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
salivary gland calculus † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
General disorders        
chest pain † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
non-cardiac chest pain † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
Hepatobiliary disorders        
cholecystitis † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
cholelithiasis † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
hepatic cirrhosis † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
hepatitis acute † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
Immune system disorders        
cryoglobulinaemia † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
Infections and infestations        
Cellulitis † 1      
# participants affected / at risk     1/361 (0.28%)     1/364 (0.27%)     1/363 (0.28%)  
pneumonia † 1      
# participants affected / at risk     0/361 (0.00%)     2/364 (0.55%)     1/363 (0.28%)  
appendicitis † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     1/363 (0.28%)  
lobar pneumonia † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     1/363 (0.28%)  
pyelonephritis † 1      
# participants affected / at risk     1/361 (0.28%)     1/364 (0.27%)     0/363 (0.00%)  
urinary tract infection † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     2/363 (0.55%)  
abscess † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
abscess limb † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
acute sinusitis † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
bacteraemia † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
cellulitis staphylococcal † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
escherichia bacteraemia † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
gastroenteritis † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
gastroenteritis viral † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
lung abscess † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
lymphangitis † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
perirectal abscess † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
respiratory tract infection † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
staphylococcal abscess † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
staphylococcal infection † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
subcutaneous abscess † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
tuberculosis † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
Injury, poisoning and procedural complications        
thermal burn † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
Metabolism and nutrition disorders        
dehydration † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
hyponatraemia † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
Musculoskeletal and connective tissue disorders        
back pain † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
costochondritis † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
intervertebral disc † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
pain in extremity † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
rheumatoid arthritis † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
Nervous system disorders        
syncope † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     3/363 (0.83%)  
convulsion † 1      
# participants affected / at risk     2/361 (0.55%)     0/364 (0.00%)     0/363 (0.00%)  
migraine † 1      
# participants affected / at risk     1/361 (0.28%)     1/364 (0.27%)     0/363 (0.00%)  
altered state of consciousness † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
global amnesia † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
Psychiatric disorders        
anxiety † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     1/363 (0.28%)  
completed suicide † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
depression † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
insomnia † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
panic attack † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
psychotic disorder † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
Renal and urinary disorders        
renal failure acute † 1      
# participants affected / at risk     2/361 (0.55%)     0/364 (0.00%)     0/363 (0.00%)  
nephrolithiasis † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
urinary retention † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
Reproductive system and breast disorders        
metrorrhagia † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
Respiratory, thoracic and mediastinal disorders        
dyspnoea † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
Skin and subcutaneous tissue disorders        
rash † 1      
# participants affected / at risk     0/361 (0.00%)     3/364 (0.82%)     2/363 (0.55%)  
pruritus † 1      
# participants affected / at risk     1/361 (0.28%)     1/364 (0.27%)     0/363 (0.00%)  
eczema † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
leukocytoclastic vasculitis † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
rash maculo-papular † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
stevens-johnson syndrome † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
Vascular disorders        
hypotension † 1      
# participants affected / at risk     0/361 (0.00%)     1/364 (0.27%)     0/363 (0.00%)  
phlebitis † 1      
# participants affected / at risk     0/361 (0.00%)     0/364 (0.00%)     1/363 (0.28%)  
thrombophlebitis † 1      
# participants affected / at risk     1/361 (0.28%)     0/364 (0.00%)     0/363 (0.00%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 11.0




  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


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