The Impact of Deferasirox on Non-Alcoholic-Steatohepatitis

NCT01278056 | Completed Phase 1 DMC

• 1 other identifier: CICL670EDE08T
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Non-alcoholic Steatohepatitis; Increased Iron Storage / Disturbed Distribution

Keywords

Non-alcoholic steatohepatitis (NASH) and increased iron storage / disturbed distribution

Outcome Measures

Primary Outcomes (2)

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

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

  Phase I: 12 weeks of treatment

• Changes in liver histology in all patients (Phase II)

  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 II: 48 weeks of treatment

Secondary Outcomes (2)

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

  Phase I: 12 weeks of treatment

• Phase II: e.g. changes in MRI and histology based assessment of hepatic steatosis, fibrosis and iron content

  Phase II: 48 weeks of treatment

Study Arms (1)

Exjade

EXPERIMENTAL

Drug: Exjade

Interventions

Exjade DRUG

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

Also known as: Deferasirox, ICL670

Exjade

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with elevated liver enzymes
• Elevated serum ferritin (females \> 300 ng/ml, males \> 450 ng/ml)
• Liver Histology consistent with a diagnosis of NASH

You may not qualify if:

• 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

Sponsors & Collaborators

• Crolll Gmbh: lead
• Estimate, GmbH: collaborator
• University of Magdeburg: collaborator

Study Sites (9)

Zollernalbklinikum

Balingen/Hechingen, 72336, Germany

Location

Charité, Virchow Klinikum

Berlin, 13353, Germany

Location

Klinikum der J. W. Goethe-Universität, Med. Klinik I

Frankfurt, 60590, Germany

Location

Universitätsklinikum Halle, Klinik & Poliklinik für Innere Medizin I

Halle, 06097, Germany

Location

Universitätsklinikum des Saarlandes

Homburg/Saar, 66421, Germany

Location

Universitätsklinikum Magdeburg, Klinik für Gastroenterologie, Hepatologie und Infektiologie

Magdeburg, 39120, Germany

Location

Universitätsklinikum Mainz, I. Medizinische Klinik und Poliklinik

Mainz, 55131, Germany

Location

Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Med. I

Regensburg, 93042, Germany

Location

Universitätsklinikum Tübingen, Medizinische Klinik IV

Tübingen, 72076, Germany

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Gerhard Treiber, PD Dr. med.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2011
• First Posted: January 17, 2011
• Study Start: March 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: July 1, 2012
• Last Updated: July 20, 2012

Record last verified: 2012-07

Locations

DE (9)