Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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
  Hide Participant Flow

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
  Hide Baseline Characteristics

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 
Overall Participants Analyzed 
[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


  Other Adverse Events
  Hide Other Adverse Events

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.

Frequency Threshold
Threshold above which other adverse events are reported   5  

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.

Other 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, other (not including serious) adverse events       
# participants affected / at risk   354/361 (98.06%)   362/364 (99.45%)   361/363 (99.45%) 
Blood and lymphatic system disorders       
anaemia † 1       
# participants affected / at risk   70/361 (19.39%)   141/364 (38.74%)   135/363 (37.19%) 
neutropenia † 1       
# participants affected / at risk   68/361 (18.84%)   62/364 (17.03%)   51/363 (14.05%) 
Eye disorders       
vision blurred † 1       
# participants affected / at risk   27/361 (7.48%)   26/364 (7.14%)   29/363 (7.99%) 
Gastrointestinal disorders       
nausea † 1       
# participants affected / at risk   112/361 (31.02%)   146/364 (40.11%)   156/363 (42.98%) 
diarrhoea † 1       
# participants affected / at risk   80/361 (22.16%)   115/364 (31.59%)   102/363 (28.10%) 
vomiting † 1       
# participants affected / at risk   38/361 (10.53%)   55/364 (15.11%)   55/363 (15.15%) 
haemorrhoids † 1       
# participants affected / at risk   13/361 (3.60%)   43/364 (11.81%)   43/363 (11.85%) 
anorectal discomfort † 1       
# participants affected / at risk   13/361 (3.60%)   30/364 (8.24%)   46/363 (12.67%) 
abdominal pain † 1       
# participants affected / at risk   34/361 (9.42%)   28/364 (7.69%)   20/363 (5.51%) 
dyspepsia † 1       
# participants affected / at risk   23/361 (6.37%)   15/364 (4.12%)   33/363 (9.09%) 
constipation † 1       
# participants affected / at risk   12/361 (3.32%)   26/364 (7.14%)   27/363 (7.44%) 
anal pruritus † 1       
# participants affected / at risk   7/361 (1.94%)   25/364 (6.87%)   31/363 (8.54%) 
dry mouth † 1       
# participants affected / at risk   15/361 (4.16%)   32/364 (8.79%)   33/363 (9.09%) 
abdominal pain upper † 1       
# participants affected / at risk   27/361 (7.48%)   20/364 (5.49%)   31/363 (8.54%) 
General disorders       
fatigue † 1       
# participants affected / at risk   206/361 (57.06%)   211/364 (57.97%)   207/363 (57.02%) 
influenza like illness † 1       
# participants affected / at risk   101/361 (27.98%)   105/364 (28.85%)   102/363 (28.10%) 
pyrexia † 1       
# participants affected / at risk   87/361 (24.10%)   108/364 (29.67%)   95/363 (26.17%) 
irritability † 1       
# participants affected / at risk   64/361 (17.73%)   68/364 (18.68%)   80/363 (22.04%) 
asthenia † 1       
# participants affected / at risk   58/361 (16.07%)   62/364 (17.03%)   56/363 (15.43%) 
chills † 1       
# participants affected / at risk   54/361 (14.96%)   65/364 (17.86%)   46/363 (12.67%) 
injection site erythema † 1       
# participants affected / at risk   33/361 (9.14%)   46/364 (12.64%)   38/363 (10.47%) 
pain † 1       
# participants affected / at risk   28/361 (7.76%)   30/364 (8.24%)   18/363 (4.96%) 
Infections and infestations       
urinary tract infection † 1       
# participants affected / at risk   13/361 (3.60%)   22/364 (6.04%)   17/363 (4.68%) 
upper respiratory tract infection † 1       
# participants affected / at risk   18/361 (4.99%)   19/364 (5.22%)   9/363 (2.48%) 
Investigations       
weight decreased † 1       
# participants affected / at risk   22/361 (6.09%)   13/364 (3.57%)   24/363 (6.61%) 
Metabolism and nutrition disorders       
anorexia † 1       
# participants affected / at risk   39/361 (10.80%)   55/364 (15.11%)   53/363 (14.60%) 
decreased appetite † 1       
# participants affected / at risk   30/361 (8.31%)   36/364 (9.89%)   36/363 (9.92%) 
Musculoskeletal and connective tissue disorders       
myalgia † 1       
# participants affected / at risk   77/361 (21.33%)   76/364 (20.88%)   54/363 (14.88%) 
arthralgia † 1       
# participants affected / at risk   68/361 (18.84%)   56/364 (15.38%)   49/363 (13.50%) 
back pain † 1       
# participants affected / at risk   43/361 (11.91%)   25/364 (6.87%)   28/363 (7.71%) 
pain in extremity † 1       
# participants affected / at risk   13/361 (3.60%)   8/364 (2.20%)   19/363 (5.23%) 
Nervous system disorders       
headache † 1       
# participants affected / at risk   142/361 (39.34%)   156/364 (42.86%)   148/363 (40.77%) 
dizziness † 1       
# participants affected / at risk   49/361 (13.57%)   50/364 (13.74%)   57/363 (15.70%) 
distrubance in attention † 1       
# participants affected / at risk   33/361 (9.14%)   29/364 (7.97%)   25/363 (6.89%) 
dysgeusia † 1       
# participants affected / at risk   14/361 (3.88%)   36/364 (9.89%)   34/363 (9.37%) 
Psychiatric disorders       
insomnia † 1       
# participants affected / at risk   111/361 (30.75%)   116/364 (31.87%)   117/363 (32.23%) 
depression † 1       
# participants affected / at risk   79/361 (21.88%)   61/364 (16.76%)   66/363 (18.18%) 
anxiety † 1       
# participants affected / at risk   44/361 (12.19%)   33/364 (9.07%)   35/363 (9.64%) 
affect lability † 1       
# participants affected / at risk   12/361 (3.32%)   5/364 (1.37%)   17/363 (4.68%) 
Respiratory, thoracic and mediastinal disorders       
cough † 1       
# participants affected / at risk   86/361 (23.82%)   76/364 (20.88%)   61/363 (16.80%) 
dyspnoea † 1       
# participants affected / at risk   50/361 (13.85%)   52/364 (14.29%)   47/363 (12.95%) 
dyspnoea exertional † 1       
# participants affected / at risk   23/361 (6.37%)   27/364 (7.42%)   26/363 (7.16%) 
pharyngolaryngeal pain † 1       
# participants affected / at risk   19/361 (5.26%)   25/364 (6.87%)   28/363 (7.71%) 
Skin and subcutaneous tissue disorders       
pruritus † 1       
# participants affected / at risk   131/361 (36.29%)   165/364 (45.33%)   181/363 (49.86%) 
rash † 1       
# participants affected / at risk   88/361 (24.38%)   129/364 (35.44%)   133/363 (36.64%) 
alopecia † 1       
# participants affected / at risk   73/361 (20.22%)   81/364 (22.25%)   83/363 (22.87%) 
dry skin † 1       
# participants affected / at risk   66/361 (18.28%)   66/364 (18.13%)   63/363 (17.36%) 
rash papular † 1       
# participants affected / at risk   15/361 (4.16%)   20/364 (5.49%)   24/363 (6.61%) 
pruritus generalised † 1       
# participants affected / at risk   13/361 (3.60%)   22/364 (6.04%)   22/363 (6.06%) 
rash erythematous † 1       
# participants affected / at risk   16/361 (4.43%)   13/364 (3.57%)   17/363 (4.68%) 
rash pruritic † 1       
# participants affected / at risk   11/361 (3.05%)   17/364 (4.67%)   16/363 (4.41%) 
eczema † 1       
# participants affected / at risk   14/361 (3.88%)   18/364 (4.95%)   10/363 (2.75%) 
rash maculo-papular † 1       
# participants affected / at risk   7/361 (1.94%)   10/364 (2.75%)   23/363 (6.34%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 11.0



  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.


  More Information