A Phase 2a Study to Evaluate Viral Kinetics and Safety of Telaprevir in Participants With Genotype 2 or 3 Hepatitis C Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec BVBA
ClinicalTrials.gov Identifier:
NCT00561015
First received: November 19, 2007
Last updated: June 7, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to assess the effect of telaprevir on early hepatitis (inflammation of the liver) C virus (HCV) viral kinetics in treatment-naive participants who are chronically (lasting a long time) infected with genotype 2 or 3 HCV.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: Telaprevir
Drug: Peg-IFN-alfa-2a + Ribavirin (Standard Treatment)
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase IIa Randomized, Partially Blinded Trial of Telaprevir (VX-950) in Treatment-Naive Subjects With Chronic Genotype 2 or 3 Hepatitis C Infection

Resource links provided by NLM:


Further study details as provided by Tibotec BVBA:

Primary Outcome Measures:
  • Change From Baseline in Log 10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level at Day 15 [ Time Frame: Baseline, Pre-dose (Day 15) ] [ Designated as safety issue: No ]
    Level of HCV RNA in plasma was measured using COBAS TaqMan HCV test v2.0 (an in vitro nucleic acid amplification test for quantitation of HCV RNA genotypes 1 through 6 in human serum or plasma, using the COBAS AmpliPrep Total Nucleic Acid Isolation Kit (TNAI) for preparation of highly purified total nucleic acid from serum or plasma and automated amplification and detection on TaqMan 48 Analyzer). Lower limit of quantification was 25 international units/milliliter (IU/ml) and limit of detection was 10 IU/ml. Assay used was reverse transcription-polymerase chain reaction (RT-PCR) methodology.

  • Maximum Plasma Concentration (Cmax) for Telaprevir on Day 1 [ Time Frame: Pre-dose Day 1 (0.5, 1, 2, 3, 4, 6, 8 hour [hr]) ] [ Designated as safety issue: No ]
    The Cmax is defined as the maximum observed analyte concentration. The Cmax was measured in nanogram/milliliter (ng/ml).

  • Time to Reach Maximum Plasma Concentration (Tmax) for Telaprevir on Day 1 [ Time Frame: Pre-dose Day 1 (0.5, 1, 2, 3, 4, 6, 8 hr) ] [ Designated as safety issue: No ]
    The Tmax is defined as the actual sampling time to reach maximum observed analyte concentration. The analyte concentration associated with Tmax is referred to as Cmax.

  • Area Under Plasma Concentration-Time Curve Over Dosing Interval (AUCtau) for Telaprevir on Day 1 [ Time Frame: Pre-dose Day 1 (0.5, 1, 2, 3, 4, 6, 8 hr) ] [ Designated as safety issue: No ]
    The AUC is defined as area under the plasma concentration-time curve over the dosing interval (8 hr), calculated by the lin-up/ log-down method.


Secondary Outcome Measures:
  • Area Under Plasma Concentration-Time Curve Over Dosing Interval (AUCtau) for Telaprevir on Day 15 [ Time Frame: Pre-dose Day 15 (0.5, 1, 2, 3, 4, 6, 8 hr) ] [ Designated as safety issue: No ]
    The AUC is defined as area under the plasma concentration-time curve over the dosing interval (8 hr), calculated by the lin-up/ log-down method.

  • Change From Baseline in Log 10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level at Week 24 and Week 26 [ Time Frame: Baseline and Week 24/26 ] [ Designated as safety issue: No ]
    Levels of HCV RNA in plasma were measured using COBAS TaqMan HCV test v2.0. Lower limit of quantification was 25 IU/ml and limit of detection was 10 IU/ml. The assay used real time RT-PCR methodology. End of treatment (EOT) for group T2 & PR24 was 26 weeks and for groups T2/PR24 and Pbo/PR24 was 24 weeks.

  • Maximum Plasma Concentration (Cmax) for Telaprevir on Day 15 [ Time Frame: Pre-dose Day 15 (0.5, 1, 2, 3, 4, 6, 8 hr) ] [ Designated as safety issue: No ]
    The Cmax is defined as the maximum observed analyte concentration. The Cmax is measured in ng/ml.

  • Minimum Plasma Concentration (Cmin) for Telaprevir on Day 15 [ Time Frame: Pre-dose Day 15 (0.5, 1, 2, 3, 4, 6, 8 hr) ] [ Designated as safety issue: No ]
    The Cmin is defined as minimum plasma concentration between 0 hr and dosing interval. The Cmin is measured in ng/ml.

  • Percentage of Participants Achieving Virological Response (HCV RNA Level < 10 IU/ml) [ Time Frame: Baseline, Day 12, 15, Week 4, 6, 14 and EOT (Week 24/26 or early discontinuation) ] [ Designated as safety issue: No ]
    Virological response was defined as having HCV RNA level less than a particular threshold that is less than 10 IU/ml (undetectable).

  • Median Time to Virological Response (HCV RNA Level < 10 IU/ml) [ Time Frame: Baseline up to EOT ] [ Designated as safety issue: No ]
    Virological response was defined as having HCV RNA level less than a particular threshold which is either less than 10 IU/ml (undetectable) or less than 25 IU/ml (unquantifiable).Time to virological response was defined as the number of days from the start of medication intake necessary to go for the first time below the threshold value. The EOT for group T2 & PR24 was 26 weeks and for groups T2/PR24 and Pbo/PR24 was 24 weeks.

  • Percentage of Participants With Viral Breakthrough [ Time Frame: Baseline, Day 12, 15 and Week 24/26 ] [ Designated as safety issue: No ]
    Viral breakthrough was defined as an increase in HCV RNA levels by more than 1 log10 in HCV RNA level from the lowest level reached, or a value of HCV RNA > 100 IU/ml in participants whose HCV RNA had previously become undetectable (< 10 IU/ml) or unquantifiable (< 25 IU/ml) during the considered treatment phase. It was considered as confirmed when the criterion for viral breakthrough is fulfilled at two or more consecutive time points or at the last observed time point in case of trial termination. The EOT for group T2 & PR24 was 26 weeks and for groups T2/PR24 and Pbo/PR24 was 24 weeks.

  • Percentage of Participants Who Demonstrated Virological Relapse [ Time Frame: 24 weeks after EOT ] [ Designated as safety issue: No ]
    Relapse was defined as confirmed detectable HCV RNA (>=10 IU/ml) during the follow-up period up to 24 weeks after last medication intake and after previous undetectable HCV RNA (< 10 IU/ml) at EOT. No relapse was defined as having no confirmed detectable HCV RNA (>=10 IU/ml) during the follow-up period and after previous undetectable HCV RNA (< 10 IU/ml) at EOT. Missing follow-up means no HCV RNA measurements during the follow-up period and after previous undetectable HCV RNA (< 10 IU/ml) at EOT. The EOT for group T2 & PR24 was 26 weeks and for groups T2/PR24 and Pbo/PR24 was 24 weeks.

  • Percentage of Participants Who Achieved Sustained Virological Response (SVR) [ Time Frame: Week 12, 24 after EOT ] [ Designated as safety issue: No ]
    The SVR was defined as having HCV RNA undetectable at EOT, not showing relapse up to follow-up Week 12 (SVR12) or follow-up Week 24 (SVR24), and HCV RNA undetectable at follow-up Week 12 (SVR12) or follow-up Week 24 (SVR24), respectively. The EOT for group T2 & PR24 was 26 weeks and for groups T2/PR24 and Pbo/PR24 was 24 weeks.


Enrollment: 52
Study Start Date: December 2007
Study Completion Date: May 2009
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TVR then Peg-IFN-alfa-2a + RBV (T2 & PR24) - Genotype 2
Participants who are never treated for chronic hepatitis C (inflammation of the liver) genotype 2 will receive telaprevir (TVR) 750 milligram (mg) tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15. Participants will then be treated with standard treatment regimen of pegylated interferon (Peg-IFN)-alfa-2a and ribavirin (RBV) from Day 15 to Week 26 (standard treatment phase). Each dose of pegylated interferon 180 microgram (mcg) will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 26 weeks.
Drug: Telaprevir
Telaprevir 750 mg tablet will be administered three times a day orally for 2 weeks.
Other Name: VX-950
Drug: Peg-IFN-alfa-2a + Ribavirin (Standard Treatment)
Standard treatment of Peg-IFN-alfa-2a (180 mcg subcutaneous injection, once weekly) and ribavirin (400 mg as oral tablet twice daily) will be administered from Day 15 to Week 24 or 26 in the T2 & PR24 - genotype 2 and 3 group and from Day 1 to Week 24 or 26 in the T2/PR24 - genotype 2 and 3 group.
Experimental: TVR with Peg-IFN-alfa-2a + RBV (T2/PR24) - Genotype 2
Participants who are never treated for CHC genotype 2 will receive TVR 750 mg tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15 along with standard treatment regimen of Peg-IFN-alfa-2a and RBV which will be continued in the standard treatment phase from Day 15 to Week 24. Each dose of Peg-IFN-alfa-2a 180 mcg will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 24 weeks.
Drug: Telaprevir
Telaprevir 750 mg tablet will be administered three times a day orally for 2 weeks.
Other Name: VX-950
Drug: Peg-IFN-alfa-2a + Ribavirin (Standard Treatment)
Standard treatment of Peg-IFN-alfa-2a (180 mcg subcutaneous injection, once weekly) and ribavirin (400 mg as oral tablet twice daily) will be administered from Day 15 to Week 24 or 26 in the T2 & PR24 - genotype 2 and 3 group and from Day 1 to Week 24 or 26 in the T2/PR24 - genotype 2 and 3 group.
Active Comparator: Pbo with Peg-IFN-alfa-2a + RBV (Pbo/PR24) - Genotype 2
Participants who are never treated for CHC genotype 2 will receive TVR matching placebo (Pbo) tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15 along with standard treatment regimen of Peg-IFN-alfa-2a and RBV which will be continued in the standard treatment phase from Day 15 to Week 24. Each dose of Peg-IFN-alfa-2a 180 mcg will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 24 weeks.
Drug: Peg-IFN-alfa-2a + Ribavirin (Standard Treatment)
Standard treatment of Peg-IFN-alfa-2a (180 mcg subcutaneous injection, once weekly) and ribavirin (400 mg as oral tablet twice daily) will be administered from Day 15 to Week 24 or 26 in the T2 & PR24 - genotype 2 and 3 group and from Day 1 to Week 24 or 26 in the T2/PR24 - genotype 2 and 3 group.
Drug: Placebo
Matching placebo tablet to telaprevir will be administered three times a day orally for 2 weeks.
Experimental: TVR then Peg-IFN-alfa-2a + RBV (T2 & PR24) - Genotype 3
Participants who are never treated for CHC genotype 3 will receive TVR 750 mg tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15. Participants will then be treated with standard treatment regimen of Peg-IFN-alfa-2a and RBV from Day 15 to Week 26 (standard treatment phase). Each dose of Peg-IFN-alfa-2a 180 mcg will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 26 weeks.
Drug: Telaprevir
Telaprevir 750 mg tablet will be administered three times a day orally for 2 weeks.
Other Name: VX-950
Drug: Peg-IFN-alfa-2a + Ribavirin (Standard Treatment)
Standard treatment of Peg-IFN-alfa-2a (180 mcg subcutaneous injection, once weekly) and ribavirin (400 mg as oral tablet twice daily) will be administered from Day 15 to Week 24 or 26 in the T2 & PR24 - genotype 2 and 3 group and from Day 1 to Week 24 or 26 in the T2/PR24 - genotype 2 and 3 group.
Experimental: TVR with Peg-IFN-alfa-2a + RBV (T2/PR24) - Genotype 3
Participants who are never treated for CHC genotype 3 received TVR 750 mg tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15 along with standard treatment regimen of Peg-IFN-alfa-2a and RBV which will be continued in the standard treatment phase from Day 15 to Week 24. Each dose of Peg-IFN-alfa-2a 180 mcg will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 24 weeks.
Drug: Telaprevir
Telaprevir 750 mg tablet will be administered three times a day orally for 2 weeks.
Other Name: VX-950
Drug: Peg-IFN-alfa-2a + Ribavirin (Standard Treatment)
Standard treatment of Peg-IFN-alfa-2a (180 mcg subcutaneous injection, once weekly) and ribavirin (400 mg as oral tablet twice daily) will be administered from Day 15 to Week 24 or 26 in the T2 & PR24 - genotype 2 and 3 group and from Day 1 to Week 24 or 26 in the T2/PR24 - genotype 2 and 3 group.
Active Comparator: Pbo with Peg-IFN-alfa-2a + RBV (Pbo/PR24) - Genotype 3
Participants who are never treated for CHC genotype 3 will receive TVR matching Pbo tablet orally 3 times a day during investigational treatment phase from Day 1 to Day 15 along with standard treatment regimen of Peg-IFN-alfa-2a and RBV which will be continued in the standard treatment phase from Day 15 to Week 24. Each dose of Peg-IFN-alfa-2a 180 mcg will be administered as a subcutaneous injection once a week. RBV will be taken orally as 400 mg tablets 2 times a day. Total duration of treatment will be 24 weeks.
Drug: Peg-IFN-alfa-2a + Ribavirin (Standard Treatment)
Standard treatment of Peg-IFN-alfa-2a (180 mcg subcutaneous injection, once weekly) and ribavirin (400 mg as oral tablet twice daily) will be administered from Day 15 to Week 24 or 26 in the T2 & PR24 - genotype 2 and 3 group and from Day 1 to Week 24 or 26 in the T2/PR24 - genotype 2 and 3 group.
Drug: Placebo
Matching placebo tablet to telaprevir will be administered three times a day orally for 2 weeks.

Detailed Description:

This is a Phase 2a multicenter (when more than one hospital or medical school team work on a medical research study), partially blinded, randomized (study drug assigned by chance) stratified (arrange in groups for analysis of results e.g., stratify by age, sex, etc.) for genotype, multiple dose study. The trial will consist of Screening period (6 weeks), Treatment period (24 or 26 weeks) and Follow-up period (24 weeks). The Treatment period will include 2 weeks investigational treatment phase and a 24 week standard treatment phase. All the eligible participants who were never treated for HCV will be enrolled for the trial and will receive the investigational treatment regimen to which they have been randomly assigned for 2 weeks. After this in the standard treatment phase participants will receive the standard treatment of care consisting of pegylated interferon (Peg-IFN)-alfa-2a 180 microgram once weekly and ribavirin (RBV) 400 milligram twice per day. Efficacy will primarily be evaluated by HCV viral load quantification. Participant's safety will be monitored throughout the study.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants chronically infected with genotype 2 or 3 hepatitis C virus (HCV) with amount of virus in the blood greater than 10,000 international units per milliliter (IU/ml)
  • Participants who were never treated for hepatitis C virus infection
  • Participants without any significant lab abnormalities
  • Participants who agree to the use of two effective methods of contraception
  • Participant who were judged to be in good health

Exclusion Criteria:

  • Participants who had contraindications for starting anti-HCV therapy
  • Participants who had history or evidence of liver cirrhosis (serious liver disorder in which connective tissue replaces normal liver tissue, and liver failure often occurs) or decompensated liver disease or hepatocellular carcinoma (type of cancer)
  • Participant infected with human immunodeficiency virus (a life-threatening infection that you can get from an infected person's blood or from having sex with an infected person) or hepatitis B virus
  • Females who are pregnant (carrying an unborn baby), planning to be pregnant or breastfeeding
  • Participants who have hypersensitivity to tartrazine
  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: NCT00561015

Locations
France
Clichy, France
Creteil N/A, France
Lyon, France
Paris, France
Vandoeuvre Les Nancy, France
Sweden
Stockholm, Sweden
United Kingdom
London, United Kingdom
Sponsors and Collaborators
Tibotec BVBA
Investigators
Study Director: Tibotec-Virco Virology BVBA Clinical Trial Tibotec BVBA
  More Information

No publications provided

Responsible Party: Tibotec BVBA
ClinicalTrials.gov Identifier: NCT00561015     History of Changes
Obsolete Identifiers: NCT00613704
Other Study ID Numbers: CR013513, VX-950-TiDP24-C209
Study First Received: November 19, 2007
Results First Received: March 8, 2013
Last Updated: June 7, 2013
Health Authority: Great Britain: Medicines and Healthcare Products Regulatory Agency
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Italy: Agenzia Italiana del Farmaco
Sweden: Lakemedelsverket (Medical Products Agency)

Keywords provided by Tibotec BVBA:
Hepatitis C, Chronic
Genotype 2
Genotype 3
Telaprevir

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

ClinicalTrials.gov processed this record on August 18, 2014