Efficacy/Safety Study of Deferiprone Compared to Deferasirox in Paediatric Patients
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| ClinicalTrials.gov Identifier: NCT01825512 |
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Recruitment Status :
Completed
First Posted : April 5, 2013
Results First Posted : April 8, 2021
Last Update Posted : May 4, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chronic Iron Overload | Drug: Deferiprone Drug: Deferasirox | Phase 3 |
Haemoglobinopathies are a group of inherited disorders characterized by structural variations of the haemoglobin molecule. Most of the patients affected require for survival chronic red blood cells transfusions to overcome ineffective erythropoiesis. Unfortunately, all chronically transfused patients become clinically iron overloaded as there is no physiological mechanism for the removal of iron from the body. The pathologic changes and clinical manifestations associated to chronic iron overload are common among all transfusional iron-overload patients, albeit best documented in patients with beta-thalassemia major. The recommended treatment consists in regular blood transfusions combined with chelating therapy to remove the harmful iron accumulation in the body.
Currently, in the clinical practice particularly in children and adolescents, the criteria leading to the choice of the chelating agent include also the adherence to therapy, thus favouring the use of oral chelators (Ceci A et al., 2011) DFP (Deferiprone) was the first oral chelator authorised in Europe in 1999 as second line treatment for the treatment of iron overload in patients with thalassaemia major when DFO (Deferoxamine) is contraindicated or inadequate. However, despite a wide experience of DFP with iron overloaded (specifically thalassaemic )patients, limited data are available for younger children. For this reason the need for additional data in younger children is expressively included in the 2009 PDCO (Paediatric Committee) Priority List.
The purpose of this study is to assess the non-inferiority of DFP compared to DFX (deferasirox)in paediatric patients affected by hereditary haemoglobinopathies requiring chronic transfusions and chelation. Non inferiority will be established in terms of percentage of patients successfully chelated, as assessed by serum ferritin levels (in all patients) and cardiac MRI T2* (in patients above 10 years of age able to have an MRI scan without sedation).
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 435 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Multicentre, Randomised, Open Label, Non-inferiority Trial to Evaluate the Efficacy and Safety of Deferiprone Compared to Deferasirox in Patients Aged From 1 Month to Less Than 18 Years Affected by Transfusion Dependent Haemoglobinopathies |
| Actual Study Start Date : | March 17, 2014 |
| Actual Primary Completion Date : | September 21, 2017 |
| Actual Study Completion Date : | September 21, 2017 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Deferiprone
75-100 mg/kg/day seven days per week
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Drug: Deferiprone
Deferiprone 80 mg/mL oral solution
Other Name: DFP |
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Active Comparator: Deferasirox
20 to 40 mg/kg/day seven days per week
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Drug: Deferasirox
Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg
Other Names:
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- Percentage of Successfully Chelated Patients [ Time Frame: at baseline and after 12 months ]Percentage of successfully chelated patients is assessed by serum ferritin levels (in all patients) and cardiac MRI T2* (in patients above 10 years of age able to perform an MRI scan without sedation)
- Liver MRI [ Time Frame: at baseline and after 12 months ]Change in liver iron concentration (measured using liver MRI), assessed as difference between value at 12 months minus value at baseline.
- Cardiac MRI T2* [ Time Frame: at baseline and after 12 months ]Change in cardiac iron concentration (measured using cardiac MRI T2*), assessed as difference between value at 12 months minus value at baseline. MRI T2* is a non-invasive method based on gradient echo (GRE) sequences, where T2* represents the spin-spin relaxation times, measured in milliseconds. The faster the curve decreases (ie, the smaller T2*), the greater amount of iron is in the tissue. Treatment success was assessed as follows: if baseline cardiac T2* was less than 20 ms, an increase of 10% or more after 1 year of treatment was defined as treatment success; if baseline cardiac T2* was more than 20 ms, any increase or a decrease of less than 10% after 1 year of treatment was defined as treatment success.
- Ferritin Level [ Time Frame: at baseline and after 12 months ]Change in serum ferritin level, assessed as difference between value at 12 months minus value at baseline.
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| Ages Eligible for Study: | 1 Month to 17 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients of both genders aged from 1 month up to less than 18 years at the time of enrolment
- Patients affected by any hereditary haemoglobinopathy requiring chronic transfusion therapy and chelation, including but not limited to thalassemia syndromes and sickle cell disease
- Patients on current treatment with deferoxamine (DFO) or DFX or DFP in a chronic transfusion program receiving at least 150 mL/kg/year of packed red blood cells (corresponding approximately to 12 transfusions);
- For patients naïve to chelation treatment: patients that have received at least 150 mL/kg of packed red blood cells (corresponding to approximately 12 transfusions) in a chronic transfusion program and with serum ferritin levels ≥ 800 ng/mL;
- Until availability of results from the PK Study (Study DEEP-1, EudraCT n. 2012-000658-67) for patients aged from 1 month to less than 6 years: known intolerance or contraindication to DFO;
- Written informed consent and patient's informed assent, relating to his/her comprehension abilities and level of maturity
Exclusion Criteria:
- Patients with intolerance or known contraindication to either DFP or DFX
- Patients receiving DFX at a dose > 40 mg/kg/day or DFP at a dose > 100 mg/kg/day at screening
- Platelet count <100.000/mm3 during the run-in phase
- Absolute neutrophils count <1.500/mm3 during the run-in phase
- Hb levels lower than 8g/dL during the run-in phase
- Evidence of abnormal liver function
- Iron overload from causes other than transfusional haemosiderosis
- Severe heart dysfunction secondary to iron overload
- Serum creatinine level > ULN (Upper Limit of Normal) for age during the run-in phase
- History of significant medical or psychiatric disorder
- The patient has received another investigational drug within 30 days prior to this clinical trial
- Fever and other signs/symptoms of infection in the 10 days before baseline assessment
- Concomitant use of trivalent cation-dependent medicinal products such as aluminium-based antacids
- Positive test for β-HCG (Human chorionic gonadotropin) and lactating female patients
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01825512
Show 22 study locations
| Study Director: | Donato Bonifazi, Dr | Consorzio per Valutazioni Biologiche e Farmacologiche | |
| Principal Investigator: | Aurelio Maggio, MD | Ospedali Riuniti Villa Sofia-Cervello |
Documents provided by Consorzio per Valutazioni Biologiche e Farmacologiche:
| Responsible Party: | Consorzio per Valutazioni Biologiche e Farmacologiche |
| ClinicalTrials.gov Identifier: | NCT01825512 |
| Other Study ID Numbers: |
DEEP-2 |
| First Posted: | April 5, 2013 Key Record Dates |
| Results First Posted: | April 8, 2021 |
| Last Update Posted: | May 4, 2021 |
| Last Verified: | October 2017 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
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chronic iron overload hereditary haemoglobinopathy beta thalassaemia major chelating agents |
deferiprone deferasirox children paediatrics |
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Hemoglobinopathies Iron Overload Iron Metabolism Disorders Metabolic Diseases Hematologic Diseases Genetic Diseases, Inborn |
Deferasirox Deferiprone Iron Chelating Agents Chelating Agents Sequestering Agents Molecular Mechanisms of Pharmacological Action |