VX-950-TiDP24-C219: A Roll Over Trial for Patients in the Control Group of the C216 Study Who Received Telaprevir Placebo

Study Overview
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Brief Summary
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The purpose of this study is to provide access to telaprevir for patients from the control group in the C216 study, who failed treatment for virologic reasons. Efficacy, safety and tolerability of telaprevir in combination with standard treatment will be evaluated.

Detailed Description
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This is an open-label (i.e all people involved know the identity of the intervention), single-arm, roll-over trial of telaprevir in combination with pegylated interferon (Peg-IFN) alfa-2a and ribavirin (RBV). The purpose of the trial is to provide access to telaprevir for patients who were randomized to the control group in the VX-950-TiDP24-C216 trial (referred to as C216 trial hereafter) and who failed therapy for virologic reasons. The efficacy, safety, and tolerability of telaprevir in combination with Peg IFN alfa 2a and RBV will be evaluated. In addition, amino acid changes from baseline in the HCV NS3 (i.e protein associated with the hepatitis C virus) protease domain will be evaluated. The trial will consist of a screening period of approximately 28 days, a 48-week treatment period, and a 24-week follow-up period. It is expected that approximately 120 patients could be eligible for enrollment. Since the C216 trial is blinded until all patients reach Week 72 (or have discontinued earlier), patients can only enter the current trial upon invitation. The investigator will receive an invitation sent by the unblinded independent virology monitor of the C216 trial for those patients of the C216 trial who were randomized to the control group and who failed therapy for virologic reasons. Next to this invitation, the patient will need to fulfill the inclusion and exclusion criteria of the current trial in order to be eligible to participate. The screening visit for the current trial can only occur after the patient completes all assessments in the C216 trial, including the Safety Follow-up Visit. Patients must not enter this trial later than 80 weeks after their first dose in the C216 trial. In the current trial, all patients will receive 12 weeks of telaprevir 750 mg every 8 hours (q8h) in combination with Peg-IFN alfa-2a and RBV at standard doses, i.e., 180 microgram once weekly and 1,000 or 1,200 mg/day (weight based), respectively, followed by 36 weeks of Peg IFN alfa 2a and RBV at standard doses. Patients with hepatitis C virus RNA levels < 25 IU/mL undetectable at the end of treatment (Week 48 or having discontinued earlier) will be followed for 24 weeks after the last dose of study medication to assess sustained virologic response (SVR). Safety/tolerability assessments will be performed and adverse events (AEs), regardless of severity, will be collected continuously until the Safety Follow-up Visit, scheduled 4 weeks after the last dose of study medication. Thereafter, only serious adverse events (SAEs) will be reported. All patients will receive 12 weeks of telaprevir 750 mg q8h (orally) in combination with Peg-IFN alfa-2a and RBV at standard doses, i.e., 180 microgram once weekly (injection) and 1,000 or 1,200 mg/day (weight-based) (orally), respectively, followed by 36 weeks of Peg IFN alfa-2a and RBV at standard doses.

Official Title
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An Open-label, Single-arm, Roll-over Trial of Telaprevir in Combination With Pegylated Interferon Alfa-2a (Pegasys) and Ribavirin (Copegus) for Subjects From the Control Group of the VX- 950-TiDP24-C216 Trial Who Failed Therapy for Virologic Reasons

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Telaprevir
* Drug: pegylated interferon (Peg-IFN) alfa-2a
* Drug: ribavirin (RBV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient from the control group of the C216 study who failed therapy for virologic reasons Patient must have completed all assessments in the C216 trial Patient must be willing to use 2 effective methods of birth control for up to 7 months after last dose of study medication Exclusion Criteria: Patient received any direct acting anti-viral HCV therapy after discontinuation of the C216 trial Patient has history of decompensated liver disease Patient has history of acute or chronic pancreatitis Patient has condition that requires use of systemic corticosteroids Patient who prematurely stopped medication for non-compliance or for whom it would be unsafe to repeat treatment Patient has history of decompensated liver disease or history of cirrhosis with hepatocellular carcinoma

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telaprevir + Standard Treatment<br>Telaprevir 750 mg orally (by mouth) every 8h for 12 weeks plus standard treatment. Standard treatment is 180 mcg subcutaneous (under the skin) injection pegylated interferon (Peg-IFN) alfa-2a and 1000-1200 mg twice daily ribavirin (RBV) for 48 weeks. | Drug: Telaprevir<br>* 750 mg orally every 8 hours (q8h) for 12 weeks<br>Drug: pegylated interferon (Peg-IFN) alfa-2a<br>* 180 microgram (mcg) by subcutaneous injection once weekly for 48 weeks.<br>Drug: ribavirin (RBV)<br>* 1,000 or 1,200 mg/day (weight based) orally twice daily for 48 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants Achieving a Sustained Virologic Response (SVR) 24 Weeks After the Last Dose of Study Drug (SVR24 Actual) | The table below shows the percentage of participants acheiving a SVR 24 weeks after the last dose of study drug defined as having plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels < 25 IU/mL, target not detected at end of treatment (EOT) AND the participant did not relapse AND the participant completed the treatment; OR if the participant had plasma HCV RNA levels of < 25 IU/mL, target not detected at EOT AND the participant did not relapse AND the participant prematurely discontinued at least one study medication, but never for the reason virologic failure. | End of trial (24 weeks after last dose, administerd at 48 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants Achieving Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values of Less Than 25 IU/ml, Target Not Detected at Different Time Points | The table below shows the percentage of participants with undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels of less than 25 IU/ml, target not detected at different time points during the study. Data was imputed for participants with missing values using the last observation carried forward (LOCF) method for missing values. | Baseline, Weeks 4, 8, 12, 24, 36, and 48, and at the end of treatment (Week 48 or at time of early discontinuation) | 
| Percentage of Participants Who Met a Virologic Stopping Rule That Required Them to Permanently Discontinue Telaprevir and Continue Pegylated Interferon (Peg-IFN) and Ribavirin (RBV) at Week 4 or Week 8 | The table below shows the percentage of participants at Week 4 or 8 who met a stopping rule defined as having a hepatitis C virus (HCV) ribonucleic acid (RNA) value >100 IU/mL. | Week 4, Week 8 | 
| Percentage of Participants Who Met a Virologic Stopping Rule That Required Them to Permanently Discontinue All Study Drugs at Week 12, 24, or 36 | The table below shows the percentage of participants at Week 12, 24, and 36 who met a stopping rule. The stopping rule at Week 12 was having hepatitis C virus (HCV) ribonucleic acid (RNA) value of >100 IU/mL and the stopping rule at Weeks 24 or 36 was having a HCV RNA value of >=25 IU/mL. | Week 12 or Weeks 24 or 36 | 
| Percentage of Participants Achieving Rapid Virologic Response (RVR) | The table below shows the percentage of participants who had a rapid virologic response (RVR) (ie, those with undetectable hepatitis C virus [HCV] ribonucleic acid [RNA values of <25 IU/mL, target not detected at Week 4 of treatment). | Week 4 | 
| Percentage of Participants Achieving Extended Rapid Virologic Response (eRVR) | The table below shows the percentage of participants who had a Extended Rapid Virologic Response (eRVR) (ie, those with undetectable hepatitis C virus [HCV] ribonucleic acid [RNA values of <25 IU/mL, target not detected at at Weeks 4 and 12 of treatment). | Weeks 4 and 12 | 
| Percentage of Participants With Viral Breakthrough | The table below shows the percentage of participants with viral breakthrough defined as a confirmed increase >1 log10 in hepatitis C virus (HCV) ribonucleic acid (RNA) level from the lowest level reached during the considered treatment phase up to the considered time point, if the lowest level reached is > 25 IU/mL, or a confirmed value of HCV RNA >100 IU/mL in participants whose HCV RNA had previously become <25 IU/mL (detected or target not detected) during the considered treatment phase. | Week 48 (Period After Telaprevir Intake) and Week 12 (Telaprevir Treatment Phase) | 
| Percentage of Participants Who Relapsed During Follow-Up | The table below shows the percentage of participants who relapsed (ie, those having confirmed detectable hepatitis C virus [HCV] ribonucleic acid [RNA] during the 24-week follow-up period after previous HCV RNA <25 IU/mL, target not detected, at end of treatment). | During Follow-Up (24 weeks after the last dose of study drug, administerd at 48 weeks) | 
| Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values Over Time | The table below shows plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) values measured over time. | Baseline, Weeks 4, 8, 12, 24, 36, 48 | 
| Change From Baseline in Log 10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level | The table below shows change from baseline in log 10 plasma HCV RNA values measured over time. | Baseline, Weeks 4, 8, 12, 24, 36, and 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C, Chronic, Telaprevir, Roll-over study