The Impact of Deferasirox on Non-Alcoholic-Steatohepatitis (DEFINE)
This study has been completed.
Sponsor:
Crolll Gmbh
Collaborators:
estimate GmbH, Augsburg
University of Magdeburg
Information provided by (Responsible Party):
Crolll Gmbh
ClinicalTrials.gov Identifier:
NCT01278056
First received: January 14, 2011
Last updated: July 19, 2012
Last verified: July 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Non-alcoholic Steatohepatitis Increased Iron Storage / Disturbed Distribution |
Drug: Exjade |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| 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 |
Resource links provided by NLM:
Further study details as provided by Crolll Gmbh:
Primary Outcome Measures:
- 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.
Secondary Outcome Measures:
- 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 ]
| Enrollment: | 5 |
| Study Start Date: | March 2010 |
| Study Completion Date: | July 2012 |
| Primary Completion Date: | March 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Exjade |
Drug: Exjade
Two dose escalating cohorts of oral administration in Phase I. Phase II: oral administration of the maximum tolerated dose.
Other Name: Deferasirox, ICL670
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria (shortened):
- Patients with elevated liver enzymes
- Elevated serum ferritin (females > 300 ng/ml, males > 450 ng/ml)
- Liver Histology consistent with a diagnosis of NASH
Exclusion Criteria (shortened):
- Alcohol intake > 140 g/week
- Established liver cirrhosis Child Pugh B or C
- Copresence of other causes of chronic liver disease
- Anemia < 10 g/dl
- Any elevation of liver enzymes > 5 ULN (ALAT, ASAT, g-GT), > 2.5 ULN (other), > 1.5 (Bilirubin)
- Serum creatinine > 1.4 mg/dl or Ccr < 60 ml/min
- Hemochromatosis
- Known allergy or contraindication to the administration of Deferasirox
- Sexually active pre-menopausal female patients who are unable to use a highly effective method of birth control. An exception is made for those who have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation.
- Patients with impaired coagulation
- History of blood transfusion during the 6 months prior to study entry
- Oral iron supplementation within the last 4 weeks of study entry
- Treatment with phlebotomy within 2 weeks of screening visit
- Desferal treatment within 1 month of the screening visit
- Patients currently or previously treated with deferiprone or Deferasirox
- Presence of a surgical or medical condition that might significantly alter the absorption, distribution, metabolism or excretion of any study drug
- Positive HIV serology
- Patients with active inflammatory diseases that may interfere with the accurate measurement of serum ferritin
- Patients with a diagnosis of a clinically relevant cataract or a previous history of clinically relevant ocular toxicity related to iron chelation
- Pregnant or breast feeding patients
- Patients treated with systemic investigational drug within 4 weeks prior or with topical investigational drug within 7 days prior to the screening visit
- Medications with proven or suspected influence on NASH such as glitazones, statins, or metformin are no exclusion criteria for study entry (insulin is not regarded to interfere with NASH).
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01278056
Locations
| Germany | |
| Zollernalbklinikum | |
| 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 | |
Sponsors and Collaborators
Crolll Gmbh
estimate GmbH, Augsburg
University of Magdeburg
Investigators
| Principal Investigator: | Gerhard Treiber, PD Dr. med. |
More Information
No publications provided
| Responsible Party: | Crolll Gmbh |
| ClinicalTrials.gov Identifier: | NCT01278056 History of Changes |
| Other Study ID Numbers: | CICL670EDE08T |
| Study First Received: | January 14, 2011 |
| Last Updated: | July 19, 2012 |
| Health Authority: | Germany: Federal Institute for Drugs and Medical Devices |
Keywords provided by Crolll Gmbh:
|
Non-alcoholic steatohepatitis (NASH) and increased iron storage / disturbed distribution |
Additional relevant MeSH terms:
|
Fatty Liver Liver Diseases Digestive System Diseases Deferasirox |
Iron Chelating Agents Chelating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 19, 2013