A Study Assessing the Efficacy and Safety of Deferasirox in Patients With Transfusion-dependent Iron Overload

Novartis

Status and phase

Completed

Phase 3

Conditions

Transfusion-dependent Iron Overload

Treatments

Drug: Deferasirox

Study type

Interventional

Funder types

Industry

Identifiers

NCT00171821

2004-003953-16 (EudraCT Number)

CICL670A2409

Details and patient eligibility

About

This study uses a single arm, multi-center, open-label trial design. The study will assess the efficacy and safety of 52 weeks of treatment with deferasirox (ICL670) in patients with evidence of transfusion induced iron overload.

Enrollment

1,784 patients

Sex

All

Ages

2+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients presenting with transfusion-dependent anemias (independent of underlying condition) with transfusional iron overload as shown by a serum ferritin level of ≥ 1000 ng/ml
Patients of either gender and aged ≥ 2 years
Female patients who have reached menarche and who are sexually active must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation.

Additional Inclusion Criteria for Adult Patients:

Written informed consent by the patient

Additional Inclusion Criteria for Pediatric Patients:

The definition of the term "pediatric" will be in accordance with local legislation. Parents or legal guardians will be fully informed by the investigator as to the requirements of the study. The pediatric patients themselves will be informed according to their capabilities in a language and terms that they are able to understand. Written informed consent will be obtained from their parents or legal guardians on the patient's behalf in accordance with the national legislation. If capable, all patients should also personally sign their written informed assent.

Exclusion criteria

Non-transfusional hemosiderosis
Patients with clinical evidence supporting the need for intensive chelation, based on the investigator's judgment
Patients with mean levels of alanine aminotransferase (ALT) > 300 U/l
Patients with uncontrolled systemic hypertension
Patients with serum creatinine above the upper limit of normal (ULN)
Significant proteinuria as indicated by a urinary protein/creatinine ratio > 0.5 (mg/mg) in second-voiding urine samples taken at both visits 1 and 2. A third sample is to be taken from patients in whom one ratio is > 0.5 (mg/mg) and one is ≤ 0.5 (mg/mg) and patients in whom the urinary protein/creatinine ratio is > 0.5 (mg/mg) in two of the three determinations are also to be excluded.
History of nephrotic syndrome
Patients with 3rd atrioventricular (A-V) block, clinically relevant Q-T interval prolongation as well as patients requiring treatment with digoxin and similar compounds or drugs which may induce prolongation of the Q-T interval
Patients with a previous history of clinically relevant ocular toxicity related to iron chelation
Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent the patient from undergoing study treatment
Patients with psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing study treatment
Pregnant or breast feeding patients
Patients treated with systemic investigational drugs within the past 4 weeks or topical investigational drugs within the past 7 days
Any other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug. The investigator should be guided by evidence of any of the following:
- history of inflammatory bowel syndrome, gastritis, ulcers, gastrointestinal or rectal bleeding;
- history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
- history of pancreatic injury or pancreatitis; indications of impaired pancreatic function/injury as indicated by abnormal lipase or amylase;
- history or presence of impaired renal function as indicated by creatinine or blood urea nitrogen (BUN) values equal or above ULN;
- history of urinary obstruction or difficulty in voiding.
History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative
History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the run-in period
Patients with positive test to HIV
Life expectancy of < 1 year