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Safety and Efficacy of Telaprevir in Combination With Peginterferon Alfa-2a and Ribavirin in Subjects Co-Infected With Hepatitis C Virus (HCV) and HIV

This study has been completed.
Sponsor:
Collaborator:
Tibotec Pharmaceutical Limited
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT00983853
First received: September 22, 2009
Last updated: August 2, 2013
Last verified: August 2013
Results First Received: August 2, 2013  
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
Conditions: Hepatitis C
HIV Infections
Interventions: Drug: telaprevir or matching placebo
Biological: peginterferon alfa-2a
Drug: ribavirin (fixed dose)
Drug: ribavirin (weight-based dose)

  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
No text entered.

Reporting Groups
  Description
Part A: T/PR

Drug: telaprevir tablet, oral, 750 mg, q8h, 12 weeks

Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks

Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks

Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing <75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks

The dose of ribavirin used (fixed versus weight-based) was region dependent.

Part A: Pbo/PR

Drug: placebo tablet, oral, 750 mg, q8h, 12 weeks

Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks

Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks

Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing <75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks

The dose of ribavirin used (fixed versus weight-based) was region dependent.

Part B: EFV-based HAART + T/PR

Drug: efavirenz, tenofovir disoproxil fumarate, and emtricitabine

Drug: telaprevir tablet, oral, 750 mg, q8h, 12 weeks

Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks

Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks

Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing <75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks

The dose of ribavirin used (fixed versus weight-based) was region dependent.

Part B: EFV-based HAART + Pbo/PR

Drug: efavirenz, tenofovir disoproxil fumarate, and emtricitabine

Drug: placebo tablet, oral, 750 mg, q8h, 12 weeks

Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks

Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks

Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing <75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks

The dose of ribavirin used (fixed versus weight-based) was region dependent.

Part B: ATV/R-based HAART + T/PR

Drug: ritonavir-boosted atazanavir, tenofovir disoproxil fumarate, and emtricitabine or lamivudine

Drug: telaprevir tablet, oral, 750 mg, q8h, 12 weeks

Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks

Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks

Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing <75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks

The dose of ribavirin used (fixed versus weight-based) was region dependent.

Part B: ATV/R-based HAART + Pbo/PR

Drug: ritonavir-boosted atazanavir, tenofovir disoproxil fumarate, and emtricitabine or lamivudine

Drug: placebo tablet, oral, 750 mg, q8h, 12 weeks

Biological: peginterferon alfa-2a subcutaneous injection, 180 μg, once weekly, 48 weeks

Drug: ribavirin (fixed dose) tablet, oral, 800 mg, b.i.d., 48 weeks

Drug: ribavirin (weight-based dose) tablet, oral, 1000 mg for subjects weighing <75 kg or 1200 mg for subjects weighing ≥75 kg, b.i.d., 48 weeks

The dose of ribavirin used (fixed versus weight-based) was region dependent.


Participant Flow:   Overall Study
    Part A: T/PR   Part A: Pbo/PR   Part B: EFV-based HAART + T/PR   Part B: EFV-based HAART + Pbo/PR   Part B: ATV/R-based HAART + T/PR   Part B: ATV/R-based HAART + Pbo/PR
STARTED   7   7 [1]   17 [1]   8   15   8 
COMPLETED   6   5   14   6   12   7 
NOT COMPLETED   1   2   3   2   3   1 
Lost to Follow-up                1                1                2                2                2                1 
Withdrawal by Subject                0                0                1                0                1                0 
Unable to come to study follow-up visits                0                1                0                0                0                0 
[1] 1 subject was randomized but not dosed



  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.
All randomized subjects who received at least 1 dose of study drug

Reporting Groups
  Description
Part A: T/PR Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
Part A: Pbo/PR Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects not receiving HAART.
Part B: EFV-based HAART + T/PR Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz(EFV)-based highly active antiretroviral therapy(HAART) for the entire 48 week study.
Part B: EFV-based HAART + Pbo/PR Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant efavirenz(EFV)-based highly active antiretroviral therapy(HAART) for the entire 48 week study.
Part B: ATV/R-based HAART + T/PR Telaprevir plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir(ATV/r)-based highly active antiretroviral therapy(HAART) for the entire 48 week study.
Part B: ATV/R-based HAART + Pbo/PR Placebo plus peginterferon alfa-2a and ribavirin for 12 weeks, followed by 36 weeks of peginterferon alfa-2a and ribavirin. Subjects receiving concomitant ritonavir-boosted atazanavir(ATV/r)-based highly active antiretroviral therapy(HAART) for the entire 48 week study.
Total Total of all reporting groups

Baseline Measures
   Part A: T/PR   Part A: Pbo/PR   Part B: EFV-based HAART + T/PR   Part B: EFV-based HAART + Pbo/PR   Part B: ATV/R-based HAART + T/PR   Part B: ATV/R-based HAART + Pbo/PR   Total 
Overall Participants Analyzed 
[Units: Participants]
 7   6   16   8   15   8   60 
Age 
[Units: Years]
Median (Full Range)
             
median (min, max)   39.4 
 (34 to 50) 
 47.5 
 (42 to 65) 
 47.5 
 (31 to 57) 
 47.0 
 (31 to 53) 
 52.0 
 (36 to 59) 
 39.0 
 (26 to 53) 
 44.5 
 (26 to 65) 
Gender 
[Units: Participants]
             
Female   1   2   0   1   2   1   7 
Male   6   4   16   7   13   7   53 
Ethnicity (NIH/OMB) 
[Units: Participants]
             
Hispanic or Latino   3   2   5   1   3   3   17 
Not Hispanic or Latino   4   4   10   7   12   5   42 
Unknown or Not Reported   0   0   1   0   0   0   1 
Race/Ethnicity, Customized 
[Units: Participants]
             
White   2   3   12   5   13   7   42 
Black/African American   4   3   3   3   2   1   16 
American Indian/Alaska Native   1   0   0   0   0   0   1 
Other   0   0   1   0   0   0   1 
Region of Enrollment 
[Units: Participants]
             
North America   7   5   13   8   9   4   46 
United States   7   5   13   8   9   4   46 
Europe   0   1   3   0   6   4   14 
Germany   0   0   1   0   1   1   3 
Spain   0   1   2   0   3   3   9 
France   0   0   0   0   2   0   2 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Proportion of Subjects Achieving Undetectable HCV RNA at Week 12   [ Time Frame: 12 weeks after first dose of study drug ]

2.  Secondary:   Proportion of Subjects Achieving Undetectable HCV RNA at Week 4 and Week 12   [ Time Frame: 4 and 12 weeks after the first dose of study drug ]

3.  Secondary:   Proportion of Subjects Who Have Undetectable HCV RNA 12 Weeks (SVR12) and 24 Weeks (SVR24) After Last Planned Dose of Study Treatment   [ Time Frame: 12 weeks after last dose of study drug ]

4.  Secondary:   Effect of Efavirenz-based (EFV) and Atazanavir-based (ATV/r) Highly Active Antiretroviral Therapy(HAART) on Telaprevir Exposure   [ Time Frame: through 12 weeks after first dose of study drug ]

5.  Secondary:   Median Trough Plasma Concentration (Ctrough) Ratios of Efavirenz and Tenofovir (Part B Only, Subjects on EFV-based HAART)   [ Time Frame: through 12 weeks after first dose of study drug ]

6.  Secondary:   Median Trough Plasma Concentration (Ctrough) Ratios of Atazanavir (ATZ), Ritonavir, and Tenofovir (Part B Only, Subjects on ATV-based HAART)   [ Time Frame: through 12 weeks after first dose of study drug ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame first dose of study drug until 4 weeks after the last dose of study drug
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5  

Reporting Groups
  Description
T/PR Pooled T/PR from Part A and Part B
Total PR Pooled PR from Part A and Part B

Other Adverse Events
    T/PR   Total PR
Total, other (not including serious) adverse events     
# participants affected / at risk   38/38 (100.00%)   22/22 (100.00%) 
Blood and lymphatic system disorders     
Neutropenia     
# participants affected / at risk   9/38 (23.68%)   5/22 (22.73%) 
Anaemia     
# participants affected / at risk   6/38 (15.79%)   3/22 (13.64%) 
Endocrine disorders     
Hypothyroidism     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Eye disorders     
Cheilitis     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Gastrointestinal disorders     
Nausea     
# participants affected / at risk   13/38 (34.21%)   5/22 (22.73%) 
Diarrhoea     
# participants affected / at risk   9/38 (23.68%)   4/22 (18.18%) 
Vomiting     
# participants affected / at risk   7/38 (18.42%)   2/22 (9.09%) 
Abdominal Pain Upper     
# participants affected / at risk   5/38 (13.16%)   0/22 (0.00%) 
Gastrooesophageal Reflux Disease     
# participants affected / at risk   0/38 (0.00%)   3/22 (13.64%) 
Anogenital Dysplasia     
# participants affected / at risk   0/38 (0.00%)   2/22 (9.09%) 
Dry Mouth     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Haemorrhoids     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
General disorders     
Chills     
# participants affected / at risk   6/38 (15.79%)   4/22 (18.18%) 
Pyrexia     
# participants affected / at risk   8/38 (21.05%)   2/22 (9.09%) 
Influenza-like Illness     
# participants affected / at risk   5/38 (13.16%)   3/22 (13.64%) 
Irritability     
# participants affected / at risk   5/38 (13.16%)   3/22 (13.64%) 
Fatigue     
# participants affected / at risk   16/38 (42.11%)   9/22 (40.91%) 
Injection Site Erythema     
# participants affected / at risk   2/38 (5.26%)   1/22 (4.55%) 
Pain     
# participants affected / at risk   1/38 (2.63%)   3/22 (13.64%) 
Malaise     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Jaundice     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Infections and infestations     
Nasopharyngitis     
# participants affected / at risk   2/38 (5.26%)   1/22 (4.55%) 
Fungal Skin Infection     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Sinusitis     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Investigations     
Weight Decreased     
# participants affected / at risk   5/38 (13.16%)   5/22 (22.73%) 
Blood Bilirubin Increased     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Metabolism and nutrition disorders     
Decreased Appetite     
# participants affected / at risk   4/38 (10.53%)   4/22 (18.18%) 
Anorexia     
# participants affected / at risk   4/38 (10.53%)   1/22 (4.55%) 
Hypertriglyceridaemia     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Hypokalaemia     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Musculoskeletal and connective tissue disorders     
Myalgia     
# participants affected / at risk   6/38 (15.79%)   5/22 (22.73%) 
Back Pain     
# participants affected / at risk   3/38 (7.89%)   1/22 (4.55%) 
Arthralgia     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Muscle Spasms     
# participants affected / at risk   0/38 (0.00%)   2/22 (9.09%) 
Nervous system disorders     
Headache     
# participants affected / at risk   14/38 (36.84%)   6/22 (27.27%) 
Dizziness     
# participants affected / at risk   8/38 (21.05%)   3/22 (13.64%) 
Paraesthesia     
# participants affected / at risk   0/38 (0.00%)   2/22 (9.09%) 
Psychiatric disorders     
Depression     
# participants affected / at risk   8/38 (21.05%)   2/22 (9.09%) 
Insomnia     
# participants affected / at risk   5/38 (13.16%)   5/22 (22.73%) 
Anxiety     
# participants affected / at risk   3/38 (7.89%)   1/22 (4.55%) 
Depressed Mood     
# participants affected / at risk   1/38 (2.63%)   3/22 (13.64%) 
Affect Lability     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Libido Decreased     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough     
# participants affected / at risk   3/38 (7.89%)   3/22 (13.64%) 
Dyspnoea Exertional     
# participants affected / at risk   1/38 (2.63%)   2/22 (9.09%) 
Pharyngeal Pain     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Skin and subcutaneous tissue disorders     
Pruritus     
# participants affected / at risk   15/38 (39.47%)   2/22 (9.09%) 
Rash     
# participants affected / at risk   5/38 (13.16%)   2/22 (9.09%) 
Alopecia     
# participants affected / at risk   4/38 (10.53%)   2/22 (9.09%) 
Dry Skin     
# participants affected / at risk   2/38 (5.26%)   1/22 (4.55%) 
Night Sweats     
# participants affected / at risk   2/38 (5.26%)   1/22 (4.55%) 
Erythema     
# participants affected / at risk   2/38 (5.26%)   0/22 (0.00%) 
Dermatitis     
# participants affected / at risk   1/38 (2.63%)   2/22 (9.09%) 
1 Term from vocabulary, MedDRA (11.0)



  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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