An Exploratory Study of Telaprevir in Treatment-Naive Participants With Chronic Genotype 4 Hepatitis C Virus Infection

A Phase IIa Randomized, Partially Blinded Trial of Telaprevir (VX-950) in Treatment-Naive Subjects With Chronic Genotype 4 Hepatitis C Infection

The purpose of this study is to evaluate the activity and safety of telaprevir on Hepatitis C Virus (HCV) Genotype 4, alone or in combination with standard therapy, that is, pegylated-interferon-alfa-2a and ribavirin in treatment-naive (never been treated before with antiretroviral therapy) participants.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Telaprevir; Drug: Pegylated-interferon-alfa-2a; Drug: Ribavirin; Drug: Placebo

Detailed Description

This is a Phase 2a, partially-blind, randomized (study drug assigned by chance) and multiple-dose study to evaluate the activity and safety of telaprevir on HCV early viral kinetics in treatment-naive participants who are chronically infected with HCV Genotype 4. The study consists of 4 parts: Screening period (6-week); Investigational Treatment period (consisting of 2-week treatment with telaprevir or telaprevir+standard treatment or placebo); Standard Treatment period (consists of 46 or 48-week standard treatment); and Follow-up period (24-week). The activity of telaprevir will be evaluated by early viral kinetic parameters along with viral response and pharmacokinetic assessments during the investigational treatment phase. Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: - Participant has chronic Genotype 4 Hepatitis C infection

• Plasma hepatitis C virus (HCV) ribonucleic acid (RNA) level greater than 10,000 International unit per milliliter (IU/mL) at Screening
• Participant never received treatment for HCV
• Participant was to be in good health (besides HCV infection), in the opinion of the Investigator, judged on the basis of medical history and physical examination (including vital signs and screening electrocardiogram [ECG]), with any chronic medical conditions under stable medical control
• Participant had to be willing to refrain from the concomitant use of any medications or substances Exclusion Criteria: - Participants with history or evidence of cirrhosis or history of suspicion of alcohol, barbiturate, or amphetamine recreational or narcotic drug use, which in the Investigator's opinion would compromise the participant's safety and/or compliance with study procedures
• Participant has human immunodeficiency virus (HIV) or hepatitis B virus (HBV) co-infection
• Female participants who are pregnant, or planning to become pregnant, or breastfeeding, and partners of female participants who are pregnant or breastfeeding
• Participant has hypersensitivity to tartrazine
• Participant had participated in any clinical trial for an investigational drug within 90 days before drug administration or participated in more than 2 drug studies in the last 12 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Telaprevir and then Pegylated-interferon-alfa-2a+Ribavirin; Telaprevir 750 milligram (mg) tablet will be administered three times a day orally for 2 weeks and after that pegylated-interferon-alfa-2a (180 microgram [mcg] subcutaneous injection [injected under the skin by way of a needle], once weekly) and ribavirin (1000-1200 mg as oral tablet daily) will be administered from Week 2 to 50.	Drug: Telaprevir; Telaprevir 750 milligram (mg) tablet will be administered three times a day orally for 2 weeks.; Drug: Pegylated-interferon-alfa-2a; Pegylated-interferon-alfa-2a (180 microgram [mcg] subcutaneous injection, once weekly) will be administered from Week 1 to Week 48 or 50.; Drug: Ribavirin; Ribavirin (1000-1200 mg as oral tablet daily) will be administered from Week 1 to Week 48 or 50.
Experimental: Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin; Telaprevir 750 mg tablet will be administered three times a day orally for 2 weeks along with pegylated-interferon-alfa-2a (180 mcg subcutaneous injection, once weekly) and ribavirin (1000-1200 mg as oral tablet daily), from Week 1 to 48.	Drug: Telaprevir; Telaprevir 750 milligram (mg) tablet will be administered three times a day orally for 2 weeks.; Drug: Pegylated-interferon-alfa-2a; Pegylated-interferon-alfa-2a (180 microgram [mcg] subcutaneous injection, once weekly) will be administered from Week 1 to Week 48 or 50.; Drug: Ribavirin; Ribavirin (1000-1200 mg as oral tablet daily) will be administered from Week 1 to Week 48 or 50.
Active Comparator: Placebo+Pegylated-interferon-alfa-2a+Ribavirin; Matching placebo tablet to telaprevir will be administered three times a day orally for 2 weeks along with pegylated-interferon-alfa 2a (180 mcg subcutaneous injection, once weekly) and ribavirin (1000-1200 mg as oral tablet daily), from Week 1 to 48.	Drug: Pegylated-interferon-alfa-2a; Pegylated-interferon-alfa-2a (180 microgram [mcg] subcutaneous injection, once weekly) will be administered from Week 1 to Week 48 or 50.; Drug: Ribavirin; Ribavirin (1000-1200 mg as oral tablet daily) will be administered from Week 1 to Week 48 or 50.; Drug: Placebo; Matching placebo tablet to telaprevir was administered three times a day orally for 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Day 15	The plasma HCV RNA levels were used to assess the antiviral activity which included viral response as either undetectable HCV RNA (that is no HCV target was detected in the plasma sample) or less than 25 International unit per milliliter (IU/mL) of HCV RNA (that is Plasma sample contained HCV RNA at a concentration below the limit of quantification [LLOQ=25 IU/mL] of the viral load assay). Plasma HCV RNA levels were measured using the COBAS TaqMan HCV test Version 2.0. This assay used real-time reverse transcription-polymerase chain reaction (RT-PCR) methodology.	Baseline and Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Viral Response (Undetectable HCV RNA)	Viral response was either defined as having undetectable HCV RNA (that is, no HCV RNA was detected in the participants' plasma samples) or less than 25 IU/mL HCV RNA from Day 15 up to end of treatment (EOT), that is Week 48/50 or early discontinuation. In Week x/y, where, x represents time frame for Telaprevir+Pegylated-interferon-alfa-2a+Ribavirin and Placebo+Pegylated-interferon-alfa-2a+Ribavirin and; y represents time frame for Telaprevir and Pegylated-interferon-alfa-2a+Ribavirin treatment group.	Day 15 up to EOT (Week 48/50 or early discontinuation)
Median Time to First Viral Response (Undetectable HCV RNA)	Time to first viral response (Undetectable HCV RNA) is defined as the number of days since the start of study medication until first time negative HCV RNA level that is less than 25 IU/mL was detected.	Up to Week 48/50
Number of Participants With Viral Breakthrough (Detectable HCV RNA)	Viral breakthrough was defined as having a confirmed increase greater than 1 log 10 in HCV RNA level from the lowest level reached, or a confirmed level of HCV RNA greater than 100 IU/mL in participants whose HCV RNA had previously become undetectable [less than 25 IU/mL]). In Week x/y, where, x represents time frame for Telaprevir+pegylated-interferon-alfa-2a+Ribavirin and Placebo+pegylated-interferon-alfa-2a+Ribavirin and y represents time frame for Telaprevir and then Pegylated-interferon-alfa-2a+Ribavirin treatment group.	Day 8, Day 12, Day 15, Week 24/26 and Week 36/38
Percentage of Participants With Sustained Viral Response (SVR)	Sustained viral response was defined as having undetectable HCV RNA at EOT (Week 48/50 or early discontinuation) and no confirmed detectable HCV RNA levels between EOT and 12 weeks (SVR12) and 24 weeks (SVR24) after the last dose of study medication.	Week 12 and 24 after the last dose of study medication
Percentage of Participants With Relapse	Relapse was defined as having confirmed detectable HCV RNA during the 24-week follow-up period in participants who had undetectable HCV RNA at EOT (Week 48/50 or early discontinuation). Participants who dropped out between 24-week follow-up after EOT were not evaluated for relapse.	Week 24 after EOT (Week 48/50 or early discontinuation)
Area Under the Serum Concentration-Time Curve (AUC)	The AUC is a measure of the serum concentration-time curve, calculated by the lin-up/log-down method.	Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15
Maximum Serum Concentration (Cmax) of Telaprevir	The Cmax is the maximum observed serum concentration, which was measured at Day 1 and 15 for telaprevir and then pegylated-interferon-alfa-2a+Ribavirin (reference) and telaprevir+pegylated-interferon-alfa-2a+Ribavirin (test).	Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15
Pre-Dose Serum Concentration (C[0h]) of Telaprevir	The C(0h) is the pre-dose serum concentration of telaprevir and then pegylated-interferon-alfa-2a+Ribavirin (reference) and telaprevir+pegylated-interferon-alfa-2a+Ribavirin (test).	0 hour (pre-dose) at Day 15
Minimum Serum Concentration (Cmin) of Telaprevir on Day 15	The Cmin is the minimum serum concentration between 0 hour and τ (τ=dosing interval) of telaprevir and then pegylated-interferon-alfa-2a+Ribavirin (reference) and telaprevir+pegylated-interferon-alfa-2a+Ribavirin (test). Cmin on Day 15 is reported here.	Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 15
Time to Reach the Maximum Serum Concentration (Tmax) of Telaprevir	The tmax is the time to reach maximum observed serum concentration of telaprevir and then pegylated-interferon-alfa-2a+Ribavirin (reference) and pegylated-interferon-alfa-2a+Ribavirin (test).	Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15
Average Steady-State Serum Concentration (Css,av) of Telaprevir	The Average steady-state serum concentration (Css,av) was calculated by AUC/τ at steady-state (τ=dosing interval) of telaprevir and then pegylated-interferon-alfa-2a+Ribavirin (reference) and telaprevir+pegylated-interferon-alfa-2a+Ribavirin (test).	Pre-dose, 0.5, 1, 2, 3, 4, 6 and 8 hours post-dose on Day 1 and 15

Collaborators and Investigators

• Sponsor: Tibotec BVBA

Publications and helpful links

General Publications

• De Meyer S, Ghys A, Dierynck I, Beumont M, Luo D, Picchio G. Virologic characterization of genotype 4 hepatitis C virus variants in patients treated with telaprevir. Virol J. 2014 May 16;11:93. doi: 10.1186/1743-422X-11-93.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): January 1, 2010
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: December 20, 2007
• First Submitted That Met QC Criteria: December 26, 2007
• First Posted (Estimate): December 27, 2007

Study Record Updates

• Last Update Posted (Estimate): September 9, 2013
• Last Update Submitted That Met QC Criteria: August 27, 2013
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Keywords: Hepatitis C; Ribavirin; Pegasys; Telaprevir; Copegus; Pegylated-interferon-alfa-2a
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Interferons; Interferon-alpha; Ribavirin; Peginterferon alfa-2a; Interferon alpha-2
• Other Study ID Numbers: CR013714; VX-950-TiDP24-C210