Telaprevir Exposure and Severe Anemia in HCV Infected Patients Treated by Tri-therapy (Ribatela)

Influence of Telaprevir Exposure on the Severe Anemia Induced by Ribavirin/Pegylated Interferon/Telaprevir Tri-therapy in HCV Infected Patients

The risk of severe anemia is increased in patients treated by tri-therapy compared to patients treated by bitherapy. The underlying mechanisms involved in this toxicity remain unexplored but could also depend on the global exposure of telaprevir. The trough concentration or AUC of telaprevir could therefore be a predictive factor of the onset of anemia in patients treated by ribavirin/PEG-INF/telaprevir. The early measurement of telaprevir and ribavirin concentrations could help to manage HCV tri-therapy to improve tolerance and SVR.

Study Overview

• Status: Terminated
• Conditions: C Hepatitis, Tri Therapy
• Intervention / Treatment: Biological: Diagnostic: protocol designed to evaluate one or more interventions aimed at identifying a disease or health condition

• Study Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

• France
  • Grenoble, France, 38043
    • Grenoble University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

48 HCV-genotype 1 infected patients (16 naive patients, 16 prior partial responders/relapsers and 16 prior null responders to ribavirin/PEG-INF treatment)

Description

Inclusion Criteria:

• Man or woman older than 18 yr. 2- HCV genotype 1 infection as confirmed by a positive viral load 6 months after the selection visit or confirmed by the mean of a liver biopsy within 1 year before screening for the study.

  3- Patient with one of the following criteria: Patient naive of any treatment against HCV infection Or Prior null responder patient: patient previously treated by ribavirin/PEG-INF for at least 12 weeks and whom HCV viral load decline was <2 log at week 12 Or Prior partial responder patient: patient previously treated by ribavirin/PEG-INF for at least 12 weeks, who never had a negative viral load while the viral load decline was >2 log at week 12 Or Prior relapser patient: patient previously treated by ribavirin/PEG-INF for 48 weeks, with a negative viral load at the end of treatment and a positive viral load 6 months later 4- Patient who has stopped his treatment for at least 12 weeks 5- Patient who had a liver biopsy or a Fibroscan within the 24 months before the start of the study with a Metavir fibrosis score F ≥ 3.

  6- Patient who fulfills criteria for telaprevir treatment as defined by the licence 7- Patients who accepts to use 2 contraceptive methods until 6 months after the end of the treatment 8- Patient who had given his written informed consent 10- Patient insured under the french social security system

Exclusion Criteria:

1- Infection/co-infection by HCV genotype different than genotype 1 2- Patient with a medical contraindication to PEG-INF or ribavirin 3- Patient with history of allergy or intolerance to telaprevir 4- Patient using contraindicated drugs 5- Patient with history of decompensated liver disease and/or presenting biochemical measurements as follows at the inclusion visit:

• International Normalized Ratio (INR) > 1,5
• Albumin <3,3 g/dl
• Total bilirubin>1,8 N apart for patient with Gilbert syndrome 6- Liver disease from other causes 7- Patient with hepatocellular carcinoma or history of cancer 8- Patient with a history of graft transplantation and treated by immunosuppressive drugs 9- Patient who are regularly treated by corticosteroids 11- Patient with hemophilia or coagulation troubles 12- HIV or HBV co-infection 14- Patient with body mass index> 30 kg/m2.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HCV tritherapy and anemia; HCV-genotype 1 infected patients	Biological: Diagnostic: protocol designed to evaluate one or more interventions aimed at identifying a disease or health condition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
telaprevir concentration and area under the curve	Day 0, Day 2, week 2, week 4, week 8 and week12

Secondary Outcome Measures

Outcome Measure	Time Frame
ribavirin concentration and area under the curve	Day 0, Day 2, week 2, week 4, week 8 and week12

Other Outcome Measures

Outcome Measure	Time Frame
viral load	Day 0

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Investigators: Principal Investigator: Jean-Pierre Zarski, MD, PhD, University Hospital, Grenoble

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: October 25, 2012
• First Submitted That Met QC Criteria: October 26, 2012
• First Posted (ESTIMATE): October 29, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): January 13, 2017
• Last Update Submitted That Met QC Criteria: January 12, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: C hepatitis, telaprevir concentration, ribavirin oncentration, anemia
• Additional Relevant MeSH Terms: Digestive System Diseases; Hematologic Diseases; Liver Diseases; Hepatitis; Anemia
• Other Study ID Numbers: 1211