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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Safety and Efficacy of Early-start Deferiprone Treatment in Infants and Young Children Newly Diagnosed With Transfusion-dependent Beta Thalassemia

Conditions
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Beta Thalassemia Major Anemia, Iron Overload

Intervention / Treatment
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* Drug: Deferiprone oral solution
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 Screening level of serum ferritin 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.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 9 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deferiprone<br>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 | Drug: Deferiprone oral solution<br>* Liquid formulation of deferiprone, with a concentration of 80 mg/mL<br>* Other names: Ferriprox;|
| Placebo Comparator: Placebo<br>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 | Drug: Placebo<br>* Liquid solution that matches deferiprone oral solution in appearance and taste<br>* Other names: Placebo for deferiprone oral solution;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of patients in each treatment group who still have a serum ferritin level < 1000 micrograms per liter (μg/L) at Month 12 | A serum ferritin level of 1000 μg/L is the threshold for when standard chelation therapy begins | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach a serum ferritin level ≥ 1000 μg/L | Without adequate chelation therapy, most patients receiving regular red blood cell transfusions are likely to exceed this level within 12 months | Up to 12 months | 
| Time to reach a labile plasma iron (LPI) value ≥ 0.6 micromoles (µM) | Without adequate chelation therapy, most patients receiving regular red blood cell transfusions are likely to exceed this level within 12 months | Up to 12 months | 
| Time to reach a transferrin saturation (TSAT) value ≥ 60% | Without adequate chelation therapy, most patients receiving regular red blood cell transfusions are likely to exceed this level within 12 months | Up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thalassemia, iron overload, chelation, deferiprone, Ferriprox