An Open-Label Study of Telaprevir Administered Every 12 or 8 Hours in Combination With One of Two Pegylated Interferons and Ribavirin in Treatment-Naive Genotype 1 Chronic Hepatitis C Participants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tibotec BVBA
ClinicalTrials.gov Identifier:
NCT00528528
First received: September 10, 2007
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to explore the efficacy, safety, tolerability, pharmacokinetics (the study of the way a drug enters and leaves the blood and tissues over time), and pharmacokinetic-pharmacodynamic relationships of telaprevir administered in two different doses in combination with two standard therapies commercially available for chronic (lasting a long time) genotype 1 Hepatitis (inflammation of the liver) C virus (HCV) infection.


Condition Intervention Phase
Chronic Hepatitis C
Drug: Telaprevir
Drug: Peg-IFN-alfa-2a
Drug: Peg-IFN-alfa-2b
Drug: Ribavirin (RBV) tablet
Drug: Ribavirin (RBV) capsule
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IIa Randomized, Open-Label Study of Telaprevir (VX-950) Administered Every 12 or Every 8 Hours in Combination With Either Peg-IFN alfa2a (Pegasys) and Ribavirin (Copegus) or Peg-IFN alfa2b (PegIntron) and Ribavirin (Rebetol) in Treatment-Naive Subjects With Chronic Genotype 1 Hepatitis C Infection

Resource links provided by NLM:


Further study details as provided by Tibotec BVBA:

Primary Outcome Measures:
  • Percentage of Participants With Virologic Response at Week 12 [ Time Frame: End of treatment (EOT) (up to Week 48) ] [ Designated as safety issue: No ]
    Virologic response was either defined as having undetectable Hepatitis C Virus (HCV) ribonucleic acid (RNA) (i.e., no HCV RNA was detected in the participants' plasma samples) or less than 25 international units/milliliter (IU/mL) HCV RNA (i.e., the participants' plasma samples contained traces of HCV RNA at a concentration below the limit of quantification of the viral load assay or no HCV RNA was detected in the samples).


Secondary Outcome Measures:
  • Time to First Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Level [ Time Frame: Baseline (Day 1) up to EOT (up to Week 48) ] [ Designated as safety issue: No ]
    Virologic response was either defined as having undetectable HCV RNA (i.e., no HCV RNA was detected in the participants' plasma samples) or less than 25 IU/mL HCV RNA (i.e., the participants' plasma samples contained traces of HCV RNA at a concentration below the limit of quantification of the viral load assay or no HCV RNA was detected in the samples).

  • Number of Participants With Viral Breakthrough at End of Treatment (EOT) [ Time Frame: EOT (up to Week 48) ] [ Designated as safety issue: No ]
    Viral breakthrough was defined as a confirmed increase of more than 1 log 10 in HCV RNA level from the lowest level reached or a confirmed value of HCV RNA more than 100 IU/mL in participants whose HCV RNA was previously less than 25 IU/mL.

  • Percentage of Participants With Partial Response [ Time Frame: Baseline (Day 1) up to EOT (up to Week 48) ] [ Designated as safety issue: No ]
    Partial response was defined as having at least 2 log drop in HCV RNA from Baseline, but not having undetectable HCV RNA (i.e., no HCV RNA is detected in the participants' plasma samples).

  • Change From Baseline in Log 10-Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values at Week 12 [ Time Frame: Baseline (pre-dose), Week 12 ] [ Designated as safety issue: No ]
    Change from baseline in log 10 of Plasma HCV RNA levels were measured using the COBAS TaqMan HCV test (lower limit of quantification 25 IU/mL). The assay used real-time reverse transcription - polymerase chain reaction (RT-PCR) methodology. HCV RNA samples were taken pre-dose of Peg-IFN administration.

  • Change From Baseline in Log 10-Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Values at End of Treatment (EOT) [ Time Frame: Baseline (pre-dose), EOT (up to Week 48) ] [ Designated as safety issue: No ]
    Change from baseline in log 10 of Plasma HCV RNA levels were measured using the COBAS TaqMan HCV test (lower limit of quantification 25 IU/mL). The assay used real-time reverse transcription - polymerase chain reaction (RT-PCR) methodology.

  • Percentage of Participants With Sustained Viral Response 24 Weeks After End of Treatment (SVR24) [ Time Frame: EOT (up to Week 48) and up to 24 weeks after EOT ] [ Designated as safety issue: No ]
    SVR24 was defined as having undetectable HCV RNA (i.e., no HCV RNA is detected in the participants' plasma samples) at EOT and no confirmed detectable HCV RNA levels between EOT and 24 weeks after the last dose of study medication.


Enrollment: 166
Study Start Date: October 2007
Study Completion Date: August 2009
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Telaprevir 750 mg with Peg-IFN-alfa-2a/RBV tablet
Telaprevir tablets at the dose of 750 milligram (mg) orally administered every 8 hours (hr) for 12 weeks, in combination with standard treatment composed of pegylated interferon (Peg-IFN)-alfa-2a solution for subcutaneous injection at the dose of 180 microgram per week (mcg/week) and ribavirin (RBV) oral tablets at the dose of 1000-1200 mg/day up to 48 weeks.
Drug: Telaprevir
Oval tablets containing 375 mg of telaprevir for oral administration.
Drug: Peg-IFN-alfa-2a
Solution containing Peg-IFN alfa2a for subcutaneous injection in a pre-filled syringe.
Drug: Ribavirin (RBV) tablet
Tablets containing 200 mg RBV for oral administration.
Experimental: Telaprevir 750 mg with Peg-IFN-alfa-2b/RBV capsule
Telaprevir tablets at the dose of 750 mg orally administered every 8 hr for 12 weeks, in combination with standard treatment composed of Peg-IFN-alfa-2b solution for subcutaneous injection at the dose of 1.5 mcg/kilogram/week (mcg/kg/week) and RBV oral capsules at the dose of 800-1200 mg/day up to 48 weeks.
Drug: Telaprevir
Oval tablets containing 375 mg of telaprevir for oral administration.
Drug: Peg-IFN-alfa-2b
Powder containing Peg-IFN-alfa-2b and solvent for solution for subcutaneous injection in a pre-filled pen.
Drug: Ribavirin (RBV) capsule
Capsules containing 200 mg RBV for oral administration.
Experimental: Telaprevir 1125 mg with Peg-IFN-alfa-2a/RBV tablet
Telaprevir tablets at the dose of 1125 mg orally administered every 12 hr for 12 weeks, in combination with standard treatment composed of Peg-IFN-alfa-2a solution for subcutaneous injection at the dose of 180 mcg/week and RBV oral tablets at the dose of 1000-1200 mg/day up to 48 weeks.
Drug: Telaprevir
Oval tablets containing 375 mg of telaprevir for oral administration.
Drug: Peg-IFN-alfa-2a
Solution containing Peg-IFN alfa2a for subcutaneous injection in a pre-filled syringe.
Drug: Ribavirin (RBV) tablet
Tablets containing 200 mg RBV for oral administration.
Experimental: Telaprevir 1125 mg with Peg-IFN-alfa-2b/RBV capsule
Telaprevir tablets at the dose of 1125 mg orally administered every 12 hr for 12 weeks, in combination with standard treatment composed of Peg-IFN-alfa-2b solution for subcutaneous injection at the dose of 1.5 mcg/kg/week and RBV oral capsules at the dose of 800-1200 mg/day up to 48 weeks.
Drug: Telaprevir
Oval tablets containing 375 mg of telaprevir for oral administration.
Drug: Peg-IFN-alfa-2b
Powder containing Peg-IFN-alfa-2b and solvent for solution for subcutaneous injection in a pre-filled pen.
Drug: Ribavirin (RBV) capsule
Capsules containing 200 mg RBV for oral administration.

Detailed Description:

This is a Phase 2a, open-label (all people know the identity of the intervention), multicenter trial (conducted in more than one center) in participants with chronic genotype 1 HCV infection. The trial consists of a Screening phase of approximately 4 weeks, a treatment phase up to 48 weeks depending on participants' individual virologic response, and a follow-up phase of at least 24 weeks. All participants will receive 12 weeks of telaprevir treatment in combination with standard therapy. At Week 12, telaprevir dosing will end and participants will continue on standard therapy only. Participants will be randomly assigned to receive one of the two different dosage regimens of telaprevir (750 milligram [mg] every 8 hours (hr), or 1125 mg every 12 hr) in combination with standard therapy (pegylated interferon [Peg-IFN]-alfa-2a and ribavirin [RBV] or Peg-IFN-alfa-2b and RBV at the standard doses). Efficacy will be evaluated by HCV Ribonucleic Acid (RNA) values, viral response, viral breakthrough, partial response, early viral kinetics and sustained viral response. Pharmacokinetics, Pharmacokinetic-pharmacodynamic relationship will also be evaluated. Safety will be monitored throughout the study duration.

  Eligibility

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

Inclusion Criteria:

  • Chronic genotype 1 Hepatitis (inflammation of the liver) C infection
  • Never been treated for Hepatitis C Viral (HCV) infection
  • No clinically significant lab abnormalities
  • Amount of HCV Ribonucleic acid (RNA) in the blood more than 10,000 international units/milliliter (IU/mL) at entry
  • Liver biopsy or "Fibroscan" test performed during screening or in the past 3 years

Exclusion Criteria:

  • Contra-indications for starting anti-HCV therapy
  • 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
  • Any evidence of significant liver disease in addition to Hepatitis C
  • Infected with Human Immunodeficiency Virus (a life-threatening infection which you can get from an infected person's blood or from having sex with an infected person) or Hepatitis B
  • Women who are pregnant (carrying an unborn baby), planning to be pregnant or breastfeeding or the partner of a woman who is pregnant or breastfeeding
  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: NCT00528528

Locations
Austria
Wien, Austria
Belgium
Brussels, Belgium
Bruxelles, Belgium
Gent, Belgium
Leuven, Belgium
Liège, Belgium
France
Angers Cedex 9, France
Clichy, France
Grenoble, France
Lille Cedex, France
Nice, France
Paris, France
Paris Cedex 12, France
Vandoeuvre Les Nancy, France
Germany
Düsseldorf, Germany
Frankfurt N/A, Germany
Freiburg, Germany
Hamburg, Germany
Hannover, Germany
Koln, Germany
Tübingen, Germany
Netherlands
Leiden, Netherlands
Nijmegen, Netherlands
Spain
Barcelona, Spain
Madrid, Spain
Valencia, Spain
Sponsors and Collaborators
Tibotec BVBA
Investigators
Study Director: Tibotec-Virco Virology BVBA Clinical Trial Tibotec BVBA
  More Information

No publications provided by Tibotec BVBA

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tibotec BVBA
ClinicalTrials.gov Identifier: NCT00528528     History of Changes
Obsolete Identifiers: NCT00614497
Other Study ID Numbers: CR013516, VX-950-TIDP24-C208, 2007-001044-44
Study First Received: September 10, 2007
Results First Received: March 18, 2013
Last Updated: June 13, 2014
Health Authority: Austria: Bundesministerium für Gesundheit
Belgium: Ministerie van Volksgezondheid - Directoraat Generaal Bescherming Volksgezondheid: geneesmiddelen
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) / Federal Institute for Drugs and Medical Devices
Italy: Agenzia Italiana del Farmaco
Netherlands: Centrale Commissie Mensgebonden Onderzoek (CCMO)
Spain: Ministerio de Sanidad y Consumo - Agencia Espanola de Medicamentos y Productos Sanitarios

Keywords provided by Tibotec BVBA:
Chronic Hepatitis C
Genotype 1
Telaprevir
Treatment-naïve
VX-950-C208
VX-950-TiDP24-C208

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferon-alpha
Ribavirin
Peginterferon alfa-2a
Peginterferon alfa-2b
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 21, 2014