Skip to main content
OpenTrials
Completed

NCT Number: NCT01278056

The Impact of Deferasirox on Non-Alcoholic-Steatohepatitis

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Non-alcoholic Steatohepatitis Digestive System Diseases Fatty Liver Increased Iron Storage / Disturbed Distribution Liver Diseases Non-alcoholic Fatty Liver Disease

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Zollernalbklinikum, Balingen/Hechingen, Germany

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Exjade

Drug

Two dose escalating cohorts of oral administration in Phase I. Phase II: oral administration of the maximum tolerated dose.

Other names: Deferasirox, ICL670

Primary outcomes

  1. Safety and tolerability of deferasirox in all patients (Phase I)

    Time frame: Phase I: 12 weeks of treatment

    Safety and tolerability assessments will consist of evaluating (serious) adverse events, laboratory parameters including hematology, chemistry; vital signs and physical examinations according to CTC.

  2. Changes in liver histology in all patients (Phase II)

    Time frame: Phase II: 48 weeks of treatment

    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 outcomes

  1. Phase I: e.g. changes in liver enzymes, serum ferritin, and hemoglobin levels

    Time frame: Phase I: 12 weeks of treatment

  2. 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

Sponsors and collaborators

Lead sponsor

Crolll Gmbh

Other

Collaborators

  • Estimate, GmbH
  • University of Magdeburg

Registry information

Official study title

The Impact of Deferasirox on Non-Alcoholic-Steatohepatitis (NASH) - a Prospective Open Label Phase I/II Trial

Acronym: DEFINE

Important dates

Study start
2010
Primary completion
2012
Study completion
2012
First posted
Jan 17, 2011
Registry last updated
Jul 20, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.