Clinical trial NCT01054573: VX-950-TiDP24-C219: A Roll Over Trial for Patients in the Control Group of the C216 Study Who Received Telaprevir Placebo
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C, Chronic
Telaprevir
Roll-over study
Lead sponsor: Janssen Infectious Diseases BVBA
Sponsor class: INDUSTRY
Collaborators: name: Vertex Pharmaceuticals Incorporated
First posted: 2010-01-22
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The Percentage of Participants Achieving a Sustained Virologic Response (SVR) 24 Weeks After the Last Dose of Study Drug (SVR24 Actual)
timeFrame: End of trial (24 weeks after last dose, administerd at 48 weeks)
Secondary outcomes:
measure: 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
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, and 48, and at the end of treatment (Week 48 or at time of early discontinuation)
measure: 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
timeFrame: Week 4, Week 8
measure: Percentage of Participants Who Met a Virologic Stopping Rule That Required Them to Permanently Discontinue All Study Drugs at Week 12, 24, or 36
timeFrame: Week 12 or Weeks 24 or 36
measure: Percentage of Participants Achieving Rapid Virologic Response (RVR)
timeFrame: Week 4
measure: Percentage of Participants Achieving Extended Rapid Virologic Response (eRVR)
timeFrame: Weeks 4 and 12
measure: Percentage of Participants With Viral Breakthrough
timeFrame: Week 48 (Period After Telaprevir Intake) and Week 12 (Telaprevir Treatment Phase)
measure: Percentage of Participants Who Relapsed During Follow-Up
timeFrame: During Follow-Up (24 weeks after the last dose of study drug, administerd at 48 weeks)
measure: Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values Over Time
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, 48
measure: Change From Baseline in Log 10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level
timeFrame: Baseline, Weeks 4, 8, 12, 24, 36, and 48
Other outcomes:
Locations:
city: Coronado
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Bradenton
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Indianapolis
country: United States
state: Indiana
city: Kansas City
country: United States
state: Missouri
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Philadelphia
country: United States
state: Pennsylvania
city: Columbia
country: United States
state: South Carolina
city: Houston
country: United States
state: Texas
city: San Antonio
country: United States
state: Texas
city: Adelaide
country: Australia
city: Clayton
country: Australia
city: Darlinghurst
country: Australia
city: Perth
country: Australia
city: Brussels
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Distrito Barao Geraldo-Campina
country: Brazil
city: Salvador
country: Brazil
city: Sao Paulo
country: Brazil
city: Montreal
country: Canada
state: Quebec
city: Clichy
country: France
city: Créteil
country: France
city: Lille Cedex
country: France
city: Pessac
country: France
city: Berlin
country: Germany
city: Frankfurt
country: Germany
city: Hamburg
country: Germany
city: Hannover
country: Germany
city: Köln
country: Germany
city: München
country: Germany
city: Petah Tiqva
country: Israel
city: Zefat
country: Israel
city: Amsterdam
country: Netherlands
city: Nijmegen
country: Netherlands
city: Bialystok
country: Poland
city: Czeladz
country: Poland
city: Warszawa
country: Poland
city: San Juan
country: Puerto Rico
city: Barcelona
country: Spain
city: Valencia
country: Spain
city: Stockholm
country: Sweden
city: Zurich N/A
country: Switzerland
city: London
country: United Kingdom
Study officials:
affiliation: Janssen Infectious Diseases BVBA
name: Janssen Infectious Diseases BVBA Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Susser S, Flinders M, Reesink HW, Zeuzem S, Lawyer G, Ghys A, Van Eygen V, Witek J, De Meyer S, Sarrazin C. Evolution of hepatitis C virus quasispecies during repeated treatment with the NS3/4A protease inhibitor telaprevir. Antimicrob Agents Chemother. 2015 May;59(5):2746-55. doi: 10.1128/AAC.04911-14. Epub 2015 Feb 23.