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Efficacy/Safety Study of Deferiprone Compared to Deferasirox in Paediatric Patients

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ClinicalTrials.gov Identifier: NCT01825512
Recruitment Status : Completed
First Posted : April 5, 2013
Last Update Posted : October 24, 2017
Sponsor:
Collaborator:
European Commission
Information provided by (Responsible Party):
Consorzio per Valutazioni Biologiche e Farmacologiche

Brief Summary:

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).


Condition or disease Intervention/treatment Phase
Chronic Iron Overload Drug: Deferiprone Drug: Deferasirox Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 393 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 : August 25, 2017
Actual Study Completion Date : September 21, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Iron

Arm Intervention/treatment
Experimental: Deferiprone
75-100 mg/kg/day seven days per week
Drug: Deferiprone
Deferiprone 80 mg/mL oral solution

Active Comparator: Deferasirox
20 to 40 mg/kg/day seven days per week
Drug: Deferasirox
Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg
Other Names:
  • Exjade
  • ATC Code:V03AC03




Primary Outcome Measures :
  1. Percentage of successfully chelated patients [ Time Frame: twelve 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)


Secondary Outcome Measures :
  1. LIC (Liver Iron Concentration) [ Time Frame: twelve months ]
    It is measured by MRI scan and will be assessed in all patients able to undergo MRI scan without sedation

  2. Safety and tolerability [ Time Frame: monthly ]
    Collection of adverse events (nature, severity, grade, duration), the monitoring of haematology, blood chemistry and urine values

  3. Health-related quality of life [ Time Frame: twelve months ]
    It is evaluated using the Child Health Questionnaire™ (CHQ) in the subgroup of patients for which the questionnaire is validated (5-18 years)

  4. Steady state concentration (Css) of DFP and DFX [ Time Frame: twelve months ]
    Assessment of drug concentrations at steady-state conditions. PK data will be analysed to confirm the influence of relevant covariates on the systemic exposure to Deferiprone.



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Ages Eligible for Study:   1 Month to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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


Locations
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Albania
Hospital 'Ihsan Çabej'
Lushnjë, Albania
Qendra Spitalore Universitare "Nene Tereza" Tirane
Tirana, Albania
Cyprus
Department of Medical and Public health Services of the Ministry of Health
Nicosia, Cyprus
Egypt
Alexandria University Hospital - Faculty of Medicine
Alexandria, Egypt
Cairo University Faculty of Medicine
Cairo, Egypt
Zagazig University Hospitals
Zagazig, Egypt
Greece
National And Kapodistrian University of Athens
Athens, Greece
Italy
Centro di Thalassemia, Ospedale Civile di Lentini
Lentini, SR, Italy
Università di Bari - Facoltà di Medicina
Bari, Italy
ASL Cagliari Ospedale Regionale per le Microcitemie
Cagliari, Italy
Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi
Catania, Italy
Presidio Ospedaliero "Annunziata", Centro di Studi della Microcitemia
Cosenza, Italy
A.O.Universitaria Meyer
Firenze, Italy
Clinica Pediatrica Policlinico di Modena
Modena, Italy
Azienda Ospedaliera di Rilievo Nazionale "Antonio Cardarelli"
Napoli, Italy
Azienda Ospedaliera di Padova
Padova, Italy
Ospedale Di Cristina
Palermo, Italy
Ospedali Riuniti Villa Sofia - Cervello
Palermo, Italy
Clinica Pediatrica Università - ASL 1 D.H per Talassemia
Sassari, Italy
Tunisia
Centre National de Greffe de Moelle Osseuse Tunis
Tunis, Tunisia
United Kingdom
Barts Health NHS Trust
London, United Kingdom
Queen's Hospital
Romford, United Kingdom
Sponsors and Collaborators
Consorzio per Valutazioni Biologiche e Farmacologiche
European Commission
Investigators
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Study Director: Donato Bonifazi, Dr Consorzio per Valutazioni Biologiche e Farmacologiche
Principal Investigator: Aurelio Maggio, MD Ospedali Riuniti Villa Sofia-Cervello

Additional Information:
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Responsible Party: Consorzio per Valutazioni Biologiche e Farmacologiche
ClinicalTrials.gov Identifier: NCT01825512     History of Changes
Other Study ID Numbers: DEEP-2
First Posted: April 5, 2013    Key Record Dates
Last Update Posted: October 24, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Consorzio per Valutazioni Biologiche e Farmacologiche:
chronic iron overload
hereditary haemoglobinopathy
beta thalassaemia major
chelating agents
deferiprone
deferasirox
children
paediatrics
Additional relevant MeSH terms:
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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