The Impact of Deferasirox on Non-Alcoholic-Steatohepatitis (DEFINE)
This is a Phase I/II open-label uncontrolled, prospective study to assess the clinical and biological effects of Deferasirox (ICL 670, Exjade®) in patients with NASH and increased iron storage / distribution of iron on liver function and liver histology.
NASH is defined clinically and histologically by elevated liver enzymes, signs of hepatic steatosis on ultrasound and magnetic resonance imaging, impaired liver function as expressed by functional breath tests, and significantly altered liver histology.
Patients will be treated in a phase I and phase II part for either 12 or 48 weeks.
Both study parts have different endpoints: in phase I the side effect profile will be evaluated while in phase II the therapeutic response will be tested. Accordingly, measures will be different.
Approximately 10 patients in phase I and 50 patients in phase II will be enrolled according to sample size calculations.
The design is an "adaptive" Two-stage design, allowing to minimize the number of patients included into the trial as well as to introduce corrections for the second stage.
Increased Iron Storage / Disturbed Distribution
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The Impact of Deferasirox on Non-Alcoholic-Steatohepatitis (NASH) - a Prospective Open Label Phase I/II Trial|
- Safety and tolerability of deferasirox in all patients (Phase I) [ Time Frame: Phase I: 12 weeks of treatment ] [ Designated as safety issue: Yes ]Safety and tolerability assessments will consist of evaluating (serious) adverse events, laboratory parameters including hematology, chemistry; vital signs and physical examinations according to CTC.
- Changes in liver histology in all patients (Phase II) [ Time Frame: Phase II: 48 weeks of treatment ] [ Designated as safety issue: No ]A decrease in the NASH activity score (NAS) of ≥1 compared to baseline will be classified as response, an unchanged score or an increase in NAS will be judged as non-response.
- Phase I: e.g. changes in liver enzymes, serum ferritin, and hemoglobin levels [ Time Frame: Phase I: 12 weeks of treatment ] [ Designated as safety issue: Yes ]
- Phase II: e.g. changes in MRI and histology based assessment of hepatic steatosis, fibrosis and iron content [ Time Frame: Phase II: 48 weeks of treatment ] [ Designated as safety issue: No ]
|Study Start Date:||March 2010|
|Study Completion Date:||July 2012|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
Two dose escalating cohorts of oral administration in Phase I. Phase II: oral administration of the maximum tolerated dose.
Other Name: Deferasirox, ICL670
|Balingen/Hechingen, Germany, 72336|
|Charité, Virchow Klinikum|
|Berlin, Germany, 13353|
|Klinikum der J. W. Goethe-Universität, Med. Klinik I|
|Frankfurt, Germany, 60590|
|Universitätsklinikum Halle, Klinik & Poliklinik für Innere Medizin I|
|Halle, Germany, 06097|
|Universitätsklinikum des Saarlandes|
|Homburg/Saar, Germany, 66421|
|Universitätsklinikum Magdeburg, Klinik für Gastroenterologie, Hepatologie und Infektiologie|
|Magdeburg, Germany, 39120|
|Universitätsklinikum Mainz, I. Medizinische Klinik und Poliklinik|
|Mainz, Germany, 55131|
|Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Med. I|
|Regensburg, Germany, 93042|
|Universitätsklinikum Tübingen, Medizinische Klinik IV|
|Tübingen, Germany, 72076|
|Principal Investigator:||Gerhard Treiber, PD Dr. med.|