Safety and Efficacy of Early Treatment With Deferiprone in Infants and Young Children

Phase 4

Completed

Brief Summary: This study is looking at the effects of giving early treatment of deferiprone to young children with beta thalassemia who have started receiving regular blood transfusions but have not yet reached the criteria for starting on iron chelation therapy. Half the patients in the study will receive deferiprone, and the other half will receive placebo, for up to 12 months.

Detailed Description: This study will give deferiprone to infants and young children with thalassemia who have started receiving regular blood transfusions but whose iron load is not yet at the level where chelation treatment would normally begin. The purpose is to see if doing this will postpone the build-up of iron without causing serious side effects. Half the children in the study will be given deferiprone at a dose that is lower than what is normally prescribed, and the other half will be given placebo. All patients will receive the assigned product three times a day for up to 12 months. Tests for signs of iron overload will be done monthly, and a patient whose iron load reaches the level where chelation therapy would normally begin will be immediately taken out of the study and started on standard chelation therapy.

Recruitment & Eligibility

Inclusion Criteria

Male or female aged ≥ 6 months to < 10 years
Confirmed diagnosis of beta-thalassemia, as determined by high performance liquid chromatography (HPLC) or DNA testing
Started on a red blood cell (RBC) transfusion regimen, with a minimum of 2 transfusions already completed
Screening level of serum ferritin (SF) greater than >200 μg/L but not more than 600 μg/L. Since SF level may be impacted by the presence of infection, it must additionally be verified that the child has had no signs of infection in the previous 7 days, including the day of screening, and that the level of C-reactive protein (CRP) is no greater than 20% higher than the normal range for the patient's age. If there are signs of infection and/or the CRP level is above this threshold, the SF level must be checked again a minimum of one week later.

Exclusion Criteria

Prior use of iron chelation
Diagnosis of hepatitis B or C, or HIV infection
Evidence of abnormal liver or kidney function at screening: serum alanine transaminase (ALT) level > 5 times upper limit of normal or creatinine levels >2 times upper limit of normal
Disorders associated with neutropenia (absolute neutrophil count < 1.5 x 10^9/L) prior to the initiation of study medication
A serious, unstable illness, as judged by the investigator, during the previous 3 months before screening/baseline visit including but not limited to hepatic, renal, gastro-enterologic, respiratory, cardiovascular, endocrinologic, neurologic or immunologic disease.
Presence of any medical condition which in the opinion of the investigator would cause participation in the study to be unwise.

Arm && Interventions

Group	Intervention	Description
Deferiprone	Deferiprone oral solution	Subjects in this group will receive deferiprone oral solution at a dosage up to 75 milligrams per kilogram of body weight (mg/kg) per day, divided into 3 equal doses
Placebo	Placebo	Subjects in this group will receive placebo solution at a volume equal to what they would receive if they were in the active arm, divided into 3 equal doses

Primary Outcome Measures

Name	Time	Method
The Percentage of Patients in Each Treatment Group Who Still Have a Serum Ferritin Level < 1000 Micrograms Per Liter (μg/L) at Month 12	12 months	Current treatment guidelines are that standard iron chelation therapy should begin after a serum ferritin level of 1000 μg/L has been reached; thus, patients who were at this level at two consecutive visits were removed from the study so that they could start on this therapy.

Secondary Outcome Measures

Name	Time	Method
Percentage of Patients With Serum Ferritin Still Below the Threshold at Different Time Points	4, 8, and 12 months	The outcome measure was the percentage of patients in each group still below the serum ferritin threshold at Months 4, 8, and 12. Without adequate chelation therapy, most patients receiving red blood cell transfusions are likely to exceed this level within a few months. However, a safety feature of the study design was that patients who reached the serum ferritin threshold were withdrawn (i.e., so that they could begin standard chelation therapy).

Locations (4): Ain Shams University Children's Hospital
🇪🇬
Cairo, Egypt
The Clinical Research Center, Faculty of Medicine, Cairo University
🇪🇬
Cairo, Egypt
Cipto Mangunkusumo National Hospital
🇮🇩
Jakarta, Indonesia
Pediatric Hospital of Cairo University
🇪🇬
Cairo, Egypt