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

Hepatitis C, Chronic Clinical Trial

— CONCISE  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01459913
• Other study ID #: VX11-950-114
• Status: Terminated
• Phase: Phase 3
• First received: October 24, 2011
• Last updated: May 14, 2015
• Start date: November 2011
• Est. completion date: January 2014

Study information

• Verified date: May 2015
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaGermany: Federal Institute for Drugs and Medical DevicesPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsAustria: Agency for Health and Food SafetyIsrael: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 239
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic

Intervention

Drug:
• Telaprevir
Tablet
• Pegylated Interferon Alfa-2a
Subcutaneous Injection
• Ribavirin
Tablet

Locations

Country	Name	City	State
Israel	Israel	Jerusalem
United States	Virginia	Fairfax	Virginia
United States	Pennsylvania	Hershey	Pennsylvania
United States	California	Los Angeles	California
United States	California	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Germany,  Israel,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12)	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.	12 weeks after last planned dose of study drug (up to Week 36)	No
Secondary	Percentage of Subjects With Sustained Viral Response 4 Weeks After Last Planned Dose of Study Drug (SVR4)	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.	4 weeks after last planned dose of study drug (up to Week 28)	No
Secondary	Percentage of Subjects With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24)	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.	24 weeks after last planned dose of study drug (up to Week 48)	No
Secondary	Percentage of Subjects With Sustained Viral Response at Week 72 (SVR72)	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.	Week 72	No
Secondary	Percentage of Subjects With Viral Relapse	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.	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	No
Secondary	Percentage of Subjects With On-Treatment Virologic Failure	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.	Baseline up to Week 48	No
Secondary	Number of Subjects With Rapid Viral Response (RVR)	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.	Week 4	No
Secondary	Number of Subjects With Extended Rapid Viral Response (eRVR)	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.	Week 4 and Week 12	No
Secondary	Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	Baseline up to Week 48	Yes