Telaprevir, Peg-IFN-alfa-2a, and RBV in Treatment-Experienced Black/African American and Non-Black/African American Subjects With Genotype 1 Chronic Hepatitis C

This study has been terminated.
(It was decided by Sponsor on 13 January 2014 to terminate study early at primary efficacy endpoint as part of a decision to modify drug development plan.)
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01467492
First received: November 3, 2011
Last updated: June 1, 2015
Last verified: June 2015
  Purpose

The purpose of this study is to evaluate the efficacy and safety of telaprevir in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) and ribavirin (RBV) in treatment-experienced Black/African American and non-Black/African American participants with Genotype 1 Chronic Hepatitis C (CHC), who have not achieved a sustained viral response with a prior course of interferon-based therapy.


Condition Intervention Phase
Hepatitis C
Drug: Telaprevir
Drug: Ribavirin
Biological: Pegylated Interferon Alfa-2a
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Phase 4 Study of Telaprevir, Peginterferon Alfa-2a (Pegasys®), and Ribavirin (Copegus®) in Treatment-Experienced Black/African American and Non-Black/African American Subjects With Genotype 1 Chronic Hepatitis C Who Have Not Achieved a Sustained Viral Response With a Prior Course of Interferon-Based Therapy

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Percentage of Participants With Sustained Viral Response 12 Weeks After Last Actual Dose of Study Drug (SVR12) [ Time Frame: 12 weeks after last actual dose of study drug (up to Week 60) ] [ Designated as safety issue: No ]
    SVR12 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels (<lower limit of quantification) at 12 weeks after last actual 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).


Secondary Outcome Measures:
  • Percentage of Participants With Sustained Viral Response 24 Weeks After Last Actual Dose of Study Drug (SVR24) [ Time Frame: 24 weeks after last actual dose of study drug (up to Week 72) ] [ Designated as safety issue: No ]
    SVR24 was defined as an undetectable HCV RNA Levels (<lower limit of quantification) at 24 weeks after last actual dose of study drug. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL.

  • Percentage of Participants 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. eRVR was defined as undetectable HCV RNA (<lower limit of quantification) at both 4 weeks and 12 weeks after the start of study treatment.

  • Percentage of Participants With Relapse [ Time Frame: 4 weeks (Wk) (up to Week 52), 12 weeks (up to Week 60) and 24 weeks (up to Week 72) after actual EOT ] [ 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. Relapse was defined as having undetectable HCV RNA (<lower limit of quantification) at actual end of treatment (EOT) and followed by detectable HCV RNA (>=lower limit of quantification) during follow-up.

  • Percentage of Participants With Virologic Breakthrough [ Time Frame: Week 2, 4, 12 and 24 ] [ 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. Virologic breakthrough on treatment was defined as an increase of at least 1 log10 from nadir or confirmed detectable HCV RNA (>=lower limit of quantification) after undetectable HCV RNA (<lower limit of quantification). Percentages are calculated by using total number in FA set as denominator, in each category.

  • Percentage of Participants With On Treatment Virologic Failure [ Time Frame: Week 2, 4, 8, 12, 16, 24, 28, 36, 40, and 48 ] [ Designated as safety issue: No ]
    On treatment virologic failure was defined as meeting any futility rule or completing assigned treatment duration and having detectable HCV RNA at EOT. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL. Futility rules: 1) Virologic breakthrough (at least 1 log10 increase from nadir or confirmed detectable HCV RNA after undetectable HCV RNA) from Day 1 through Week 24 or 48 (depending on treatment duration); 2) HCV RNA >1000 IU/mL during Weeks 4 to 12, inclusive; 3) Detectable HCV RNA after Week 12. Percentages are calculated by using total number in FA set as denominator, in each category.

  • Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to Week 52 ] [ Designated as safety issue: Yes ]
    AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes SAE as well as Non-SAEs. SAE (subset of AE): 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.

  • Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region [ Time Frame: up to Week 72 ] [ Designated as safety issue: No ]
    Sequence analysis of the HCV NS3-4A region was performed to monitor telaprevir-resistant variants. HCV RNA was isolated from the plasma, amplified by reverse transcription-polymerase chain reaction (RT-PCR), and sequenced (sequencing assay limit of detection HCV RNA >=1000 IU/mL). Results of this outcome measure were to be reported for overall participants instead of by race and by prior response.


Other Outcome Measures:
  • Plasma Concentration of Telaprevir, Peginterferon Alfa-2a (Peg-IFN) and Ribavirin (RBV) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Enrollment: 121
Study Start Date: January 2012
Study Completion Date: May 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Black
Telaprevir 750 milligram (mg) tablet 3 times per day for 12 weeks in combination with Peg-IFN-alfa-2a 180 microgram per week (mcg/week) subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 milligram per day (mg/day) (for participants weighing <75 kilograms [kg]) or 1200 mg/day (for participants weighing >=75 kg) for 24 or 48 weeks.
Drug: Telaprevir
Tablet
Other Name: Incivek, VX-950
Drug: Ribavirin
Tablet
Other Name: Copegus®, RBV
Biological: Pegylated Interferon Alfa-2a
Subcutaneous Injection
Other Name: Pegasys®, Peg-IFN-Alfa-2a
Experimental: Non-Black
Telaprevir 750 mg tablet 3 times per day 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 participants weighing <75 kg) or 1200 mg/day (for participants weighing >=75 kg) for 24 or 48 weeks.
Drug: Telaprevir
Tablet
Other Name: Incivek, VX-950
Drug: Ribavirin
Tablet
Other Name: Copegus®, RBV
Biological: Pegylated Interferon Alfa-2a
Subcutaneous Injection
Other Name: Pegasys®, Peg-IFN-Alfa-2a

Detailed Description:

This is a single-arm, open-label, multicenter study of treatment-experienced participants with Genotype 1 CHC, who self-identified as Black/African American (Group A) or who did not self-identify as Black/African American (Group B). Participants did not achieve a sustained virologic response 24 weeks after at least 1 prior course of Peg-IFN-alfa-2a/RBV therapy of standard duration, and have 1 of the following viral responses:

  • Prior relapse: Participant had a documented undetectable hepatitis C virus ribonucleic acid (HCV RNA) level at the planned end of treatment of at least 42 weeks duration (HCV RNA evaluated anytime between 3 weeks before and 6 weeks after the last dose of Peg IFN-alfa-2a or RBV).
  • Prior null response: Participant had a <2-log10 decrease in HCV RNA at 12 weeks, during prior Peg IFN-alfa-2a/RBV treatment, but never achieved undetectable HCV RNA while on treatment.
  • Prior partial response: Participant had a >=2-log10 decrease in HCV RNA at 12 weeks, during prior Peg IFN-alfa-2a/RBV treatment, but never achieved undetectable HCV RNA while on treatment.
  Eligibility

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

Inclusion Criteria:

  • Participants self-identify as Black/African American (Group A) or did not self-identify as Black/African American (Group B)
  • Participants have Genotype 1 CHC and laboratory evidence of hepatitis C virus (HCV) infection for at least 6 months
  • Participants did not achieve sustained viral response 24 weeks after last dose of study drug (SVR24), after at least 1 prior course of Peg-IFN-alfa-2a/RBV therapy of standard duration

Exclusion Criteria:

  • Participants have received previous treatment with telaprevir or any other protease inhibitor(s) for CHC
  • Participants who have evidence of hepatic decompensation
  • Participants have diagnosed or suspected hepatocellular carcinoma
  • Participants have any other cause of significant liver disease in addition to HCV
  • Participants are currently abusing illicit drugs or alcohol, or have history of illicit substance or alcohol abuse within 2 years before the screening visit
  • Participants who participated in any investigational drug study within 90 days before dosing
  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: NCT01467492

  Show 27 Study Locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Investigators
Study Director: Medical Monitor Vertex Pharmaceuticals Incorporated
  More Information

No publications provided

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01467492     History of Changes
Other Study ID Numbers: VX11-950-116
Study First Received: November 3, 2011
Results First Received: June 1, 2015
Last Updated: June 1, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Vertex Pharmaceuticals Incorporated:
VX-950, Incivek

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis, Chronic
Digestive System Diseases
Enterovirus Infections
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
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 29, 2015