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

Hepatitis C, Chronic Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00561015
• Other study ID #: CR013513
• Secondary ID: VX-950-TiDP24-C2
• Status: Completed
• Phase: Phase 2
• First received: November 19, 2007
• Last updated: June 7, 2013
• Start date: December 2007
• Est. completion date: May 2009

Study information

• Verified date: June 2013
• Source: Tibotec BVBA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Great Britain: Medicines and Healthcare Products Regulatory AgencyFrance: Agence Française de Sécurité Sanitaire des Produits de SantéItaly: Agenzia Italiana del FarmacoSweden: Lakemedelsverket (Medical Products Agency)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Other known NCT identifiers

• NCT00613704

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: May 2009
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic

Intervention

Drug:
• Telaprevir
Telaprevir 750 mg tablet will be administered three times a day orally for 2 weeks.
• 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.
• Placebo
Matching placebo tablet to telaprevir will be administered three times a day orally for 2 weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Tibotec BVBA

Countries where clinical trial is conducted

France,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Log 10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level at Day 15	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.	Baseline, Pre-dose (Day 15)	No
Primary	Maximum Plasma Concentration (Cmax) for Telaprevir on Day 1	The Cmax is defined as the maximum observed analyte concentration. The Cmax was measured in nanogram/milliliter (ng/ml).	Pre-dose Day 1 (0.5, 1, 2, 3, 4, 6, 8 hour [hr])	No
Primary	Time to Reach Maximum Plasma Concentration (Tmax) for Telaprevir on Day 1	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.	Pre-dose Day 1 (0.5, 1, 2, 3, 4, 6, 8 hr)	No
Primary	Area Under Plasma Concentration-Time Curve Over Dosing Interval (AUCtau) for Telaprevir on Day 1	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.	Pre-dose Day 1 (0.5, 1, 2, 3, 4, 6, 8 hr)	No
Secondary	Area Under Plasma Concentration-Time Curve Over Dosing Interval (AUCtau) for Telaprevir on Day 15	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.	Pre-dose Day 15 (0.5, 1, 2, 3, 4, 6, 8 hr)	No
Secondary	Change From Baseline in Log 10 Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level at Week 24 and Week 26	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.	Baseline and Week 24/26	No
Secondary	Maximum Plasma Concentration (Cmax) for Telaprevir on Day 15	The Cmax is defined as the maximum observed analyte concentration. The Cmax is measured in ng/ml.	Pre-dose Day 15 (0.5, 1, 2, 3, 4, 6, 8 hr)	No
Secondary	Minimum Plasma Concentration (Cmin) for Telaprevir on Day 15	The Cmin is defined as minimum plasma concentration between 0 hr and dosing interval. The Cmin is measured in ng/ml.	Pre-dose Day 15 (0.5, 1, 2, 3, 4, 6, 8 hr)	No
Secondary	Percentage of Participants Achieving Virological Response (HCV RNA Level < 10 IU/ml)	Virological response was defined as having HCV RNA level less than a particular threshold that is less than 10 IU/ml (undetectable).	Baseline, Day 12, 15, Week 4, 6, 14 and EOT (Week 24/26 or early discontinuation)	No
Secondary	Median Time to Virological Response (HCV RNA Level < 10 IU/ml)	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.	Baseline up to EOT	No
Secondary	Percentage of Participants With Viral Breakthrough	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.	Baseline, Day 12, 15 and Week 24/26	No
Secondary	Percentage of Participants Who Demonstrated Virological Relapse	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.	24 weeks after EOT	No
Secondary	Percentage of Participants Who Achieved Sustained Virological Response (SVR)	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.	Week 12, 24 after EOT	No