Clinical trial NCT01716403: Telaprevir Exposure and Severe Anemia in HCV Infected Patients Treated by Tri-therapy
Official title: Influence of Telaprevir Exposure on the Severe Anemia Induced by Ribavirin/Pegylated Interferon/Telaprevir Tri-therapy in HCV Infected Patients
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: C Hepatitis, Tri Therapy
Keywords: C hepatitis, telaprevir concentration, ribavirin oncentration, anemia
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2012-10-29
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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)

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: telaprevir concentration and area under the curve
timeFrame: Day 0, Day 2, week 2, week 4, week 8 and week12
Secondary outcomes:
measure: ribavirin concentration and area under the curve
timeFrame: Day 0, Day 2, week 2, week 4, week 8 and week12
Other outcomes:
measure: viral load
timeFrame: Day 0
Locations:
city: Grenoble
country: France
facility: Grenoble University Hospital
Study officials:
affiliation: University Hospital, Grenoble
name: Jean-Pierre Zarski, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: