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

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

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.

Study Overview

• Status: Completed
• Conditions: Iron Overload; Beta Thalassemia Major Anemia
• Intervention / Treatment: Drug: Deferiprone oral solution; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Pediatric Hospital of Cairo University
  • Cairo, Egypt
    • Ain Shams University Children's Hospital
  • Cairo, Egypt
    • The Clinical Research Center, Faculty of Medicine, Cairo University
• Indonesia
  • Jakarta, Indonesia
    • Cipto Mangunkusumo National Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 9 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female aged ≥ 6 months to < 10 years
2. Confirmed diagnosis of beta-thalassemia, as determined by high performance liquid chromatography (HPLC) or DNA testing
3. Started on a red blood cell (RBC) transfusion regimen, with a minimum of 2 transfusions already completed
4. 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:

1. Prior use of iron chelation
2. Diagnosis of hepatitis B or C, or HIV infection
3. 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
4. Disorders associated with neutropenia (absolute neutrophil count < 1.5 x 10^9/L) prior to the initiation of study medication
5. 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.
6. Presence of any medical condition which in the opinion of the investigator would cause participation in the study to be unwise.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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	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.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With Serum Ferritin Still Below the Threshold at Different Time Points	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).	4, 8, and 12 months

Collaborators and Investigators

• Sponsor: Chiesi Canada Corp
• Investigators: Principal Investigator: Mohsen El Alfy, MD, Ain shams university

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2018
• Primary Completion (Actual): September 29, 2020
• Study Completion (Actual): September 29, 2020

Study Registration Dates

• First Submitted: July 9, 2018
• First Submitted That Met QC Criteria: July 9, 2018
• First Posted (Actual): July 19, 2018

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: iron overload; chelation; Ferriprox; thalassemia; deferiprone
• Additional Relevant MeSH Terms: Metabolic Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Iron Metabolism Disorders; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Iron Overload; Thalassemia; beta-Thalassemia; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Pharmaceutical Solutions; Deferiprone
• Other Study ID Numbers: LA55-0417

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No