Efficacy of a 12-Week Regimen of Telaprevir, Pegylated Interferon, and Ribavirin in Treatment-Naive and Prior Relapser Subjects With Interleukin28B (IL28B) CC Genotype (CONCISE)

This study has been terminated.
(The study was terminated early by the sponsor on 13 January 2014 due to a decision to modify the drug development plan.)
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01459913
First received: October 24, 2011
Last updated: May 14, 2015
Last verified: May 2015
  Purpose

The purpose of this study is to evaluate if a 12-week total regimen of telaprevir in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) and ribavirin (RBV) (T12/PR12) is safe and effective in subjects who have the interleukin-28B (IL28B) CC genotype. The subjects enrolled in this study will have chronic hepatitis C virus (HCV) infection and will not have cirrhosis of the liver.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: Telaprevir
Drug: Pegylated Interferon Alfa-2a
Drug: Ribavirin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 3b Study of 2 Treatment Durations of Telaprevir, Peg-IFN (Pegasys®), and Ribavirin (Copegus®) in Treatment-Naive and Prior Relapser Subjects With Genotype 1 Chronic Hepatitis C and IL28B CC Genotype

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Percentage of Subjects With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) [ Time Frame: 12 weeks after last planned dose of study drug (up to Week 36) ] [ Designated as safety issue: No ]
    SVR12 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at 12 weeks after last planned dose of study drug. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL) and the lower limit of detection was 10 IU/mL. This outcome was planned to be assessed only in "Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized)" and "Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized)" reporting groups.


Secondary Outcome Measures:
  • Percentage of Subjects With Sustained Viral Response 4 Weeks After Last Planned Dose of Study Drug (SVR4) [ Time Frame: 4 weeks after last planned dose of study drug (up to Week 28) ] [ Designated as safety issue: No ]
    SVR4 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at 4 weeks after last planned dose of study treatment. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL) and the lower limit of detection was 10 IU/mL. This outcome was planned to be assessed only in "Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized)" and "Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized)" reporting groups.

  • Percentage of Subjects With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24) [ Time Frame: 24 weeks after last planned dose of study drug (up to Week 48) ] [ Designated as safety issue: No ]
    SVR24 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at 24 weeks after last planned dose of study treatment. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL) and the lower limit of detection was 10 IU/mL. This outcome was planned to be assessed only in "Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized)" and "Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized)" reporting groups.

  • Percentage of Subjects With Sustained Viral Response at Week 72 (SVR72) [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    SVR72 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Week 72. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL) and the lower limit of detection was 10 IU/mL. This outcome was planned to be assessed only in "Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized)" and "Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized)" reporting groups.

  • Percentage of Subjects With Viral Relapse [ Time Frame: After last dose of study drug up to 4 weeks (up to Week 28), 12 weeks (up to Week 36), 24 weeks (up to Week 48) antiviral follow-up ] [ Designated as safety issue: No ]
    Viral relapse was defined as having detectable HCV RNA during antiviral follow-up in subjects who had HCV RNA less than (<) lower limit of quantification (LLOQ) at end of treatment. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The LLOQ was 25 IU/mL and the lower limit of detection was 10 IU/mL. This outcome was planned to be assessed only in "Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized)" and "Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized)" reporting groups.

  • Percentage of Subjects With On-Treatment Virologic Failure [ Time Frame: Baseline up to Week 48 ] [ Designated as safety issue: No ]
    On-treatment virologic failure was defined as subjects who met futility (as per investigator discretion) or who completed the assigned treatment duration and had detectable HCV RNA at planned end of treatment (up to 48 weeks). This outcome was planned to be assessed in all reporting groups and results were to be reported for total arm as well.

  • Number of Subjects With Rapid Viral Response (RVR) [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. RVR was defined as undetectable HCV RNA 4 weeks after the start of study treatment. This outcome was planned to be assessed only in "Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized)" and "Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized)" reporting groups.

  • Number of Subjects With Extended Rapid Viral Response (eRVR) [ Time Frame: Week 4 and Week 12 ] [ Designated as safety issue: No ]
    The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. eRVR was defined as undetectable HCV RNA at both 4 weeks and 12 weeks after the start of study treatment. This outcome was planned to be assessed only in "Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized)" and "Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized)" reporting groups.

  • Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 48 ] [ Designated as safety issue: Yes ]
    AE: any adverse change from the subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording or clinical laboratory assessment value which occurs during the course of the study, whether it is considered related to the study drug or not. An adverse event includes any newly occurring event or previous condition that has increased in severity or frequency since the administration of study drug. SAE: medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. "Study drug" includes all investigational agents administered during the course of the study.


Enrollment: 239
Study Start Date: November 2011
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized)
Telaprevir 1125 milligram (mg) tablet twice 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 12 weeks. Only subjects who completed initial 12 week of telaprevir and Peg-IFN/RBV and met rapid viral response (RVR, undetectable Hepatitis C Virus [HCV] Ribonucleic Acid [RNA] at Week 4) criteria, were randomized in this group, as planned, and did not receive any further treatment.
Drug: Telaprevir
Tablet
Other Names:
  • INCIVEK
  • INCIVO
  • VX-950
Drug: Pegylated Interferon Alfa-2a
Subcutaneous Injection
Other Names:
  • Pegasys
  • Peg-IFN-Alfa-2a
Drug: Ribavirin
Tablet
Other Names:
  • Copegus
  • RBV
Experimental: Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized)
Telaprevir 1125 mg tablet twice 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 weeks. Only subjects who completed initial 12 week of telaprevir and Peg-IFN/RBV and met RVR criteria, were randomized in this group, as planned.
Drug: Telaprevir
Tablet
Other Names:
  • INCIVEK
  • INCIVO
  • VX-950
Drug: Pegylated Interferon Alfa-2a
Subcutaneous Injection
Other Names:
  • Pegasys
  • Peg-IFN-Alfa-2a
Drug: Ribavirin
Tablet
Other Names:
  • Copegus
  • RBV
Experimental: Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Non Randomized)
Telaprevir 1125 mg tablet twice 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 weeks. Only subjects with RVR who permanently discontinued telaprevir, Peg-IFN-alfa-2a, or RBV treatment before Week 12, and had extended rapid viral response (eRVR, undetectable HCV RNA at Weeks 4 and 12), were included in this group, as planned.
Drug: Telaprevir
Tablet
Other Names:
  • INCIVEK
  • INCIVO
  • VX-950
Drug: Pegylated Interferon Alfa-2a
Subcutaneous Injection
Other Names:
  • Pegasys
  • Peg-IFN-Alfa-2a
Drug: Ribavirin
Tablet
Other Names:
  • Copegus
  • RBV
Experimental: Telaprevir 12 Wk +Peg-IFN-alfa-2a,RBV 48 Wk (Non Randomized)
Telaprevir 1125 mg tablet twice 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 48 weeks. Only subjects with no RVR or no RVR assessment, and subjects with RVR who permanently discontinued telaprevir, Peg-IFN-alfa-2a, or RBV treatment before Week 12, who did not have eRVR or eRVR assessment, were included in this group, as planned.
Drug: Telaprevir
Tablet
Other Names:
  • INCIVEK
  • INCIVO
  • VX-950
Drug: Pegylated Interferon Alfa-2a
Subcutaneous Injection
Other Names:
  • Pegasys
  • Peg-IFN-Alfa-2a
Drug: Ribavirin
Tablet
Other Names:
  • Copegus
  • RBV

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female subjects, 18 to 70 years of age, inclusive
  • Treatment-naive OR subjects (prior relapsers) may be included who did not achieve sustained viral response 24 weeks after last planned dose of study drug (SVR24) after at least 1 prior course of Peg-IFN/RBV therapy of standard duration and had a documented undetectable HCV RNA level at the planned end of treatment of at least 42-week duration
  • Subjects have IL28B CC genotype determined during screening
  • Subjects have genotype 1 chronic hepatitis C and laboratory evidence of HCV infection for at least 6 months, defined by (1) documented HCV serology test at least 6 months before the first screening visit demonstrating the presence of anti-HCV antibody, or (2) documented presence of HCV RNA by a sensitive and specific assay at least 6 months before the first screening visit, or (3) documented histologic evidence of chronic hepatitis C demonstrated by fibrosis on a standardized histologic grading system at least 6 months before the first screening visit. If only inflammation is present in the liver histologic report, then 6 months of laboratory evidence is required

Exclusion Criteria:

  • Subjects have received previous treatment with telaprevir or any other protease inhibitor(s) for chronic hepatitis C
  • Subjects who did not achieve SVR24 after at least 1 prior course of Peg-IFN/RBV therapy of standard duration and never achieved undetectable HCV RNA while on treatment
  • Subjects have evidence of hepatic decompensation
  • Subjects have evidence of cirrhosis
  • Subjects have diagnosed or suspected hepatocellular carcinoma
  • Subjects have any other cause of significant liver disease in addition to hepatitis C, which may include but is not limited to malignancy with hepatic involvement, hepatitis B, drug or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, nonalcoholic steatohepatitis, or primary biliary cirrhosis. Steatosis is allowed if clinically asymptomatic
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01459913

  Show 83 Study Locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Investigators
Study Director: Mark Friedman, M.D. Vertex Pharmaceuticals Incorporated
  More Information

No publications provided

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01459913     History of Changes
Other Study ID Numbers: VX11-950-114
Study First Received: October 24, 2011
Results First Received: January 26, 2015
Last Updated: May 14, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Austria: Agency for Health and Food Safety
Israel: Ministry of Health

Keywords provided by Vertex Pharmaceuticals Incorporated:
VX-950
INCIVEK
INCIVO

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Hepatitis C, Chronic
Digestive System Diseases
Flaviviridae Infections
Hepatitis, Chronic
Hepatitis, Viral, Human
Liver Diseases
RNA Virus Infections
Virus Diseases
Interferon-alpha
Interferons
Peginterferon alfa-2a
Ribavirin
Anti-Infective Agents
Antimetabolites
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2015