The Impact of Deferasirox on Non-Alcoholic-Steatohepatitis (DEFINE)

Crolll

Status and phase

Completed

Phase 2

Phase 1

Conditions

Increased Iron Storage / Disturbed Distribution

Non-alcoholic Steatohepatitis

Treatments

Drug: Exjade

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01278056

CICL670EDE08T

Details and patient eligibility

About

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.

Enrollment

5 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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).