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

Primary Purpose

Chronic Iron Overload

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Deferiprone
Deferasirox
Sponsored by
Consorzio per Valutazioni Biologiche e Farmacologiche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Iron Overload focused on measuring chronic iron overload, hereditary haemoglobinopathy, beta thalassaemia major, chelating agents, deferiprone, deferasirox, children, paediatrics

Eligibility Criteria

1 Month - 17 Years (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hospital 'Ihsan Çabej'
  • Qendra Spitalore Universitare "Nene Tereza" Tirane
  • Department of Medical and Public health Services of the Ministry of Health
  • Alexandria University Hospital - Faculty of Medicine
  • Cairo University Faculty of Medicine
  • Zagazig University Hospitals
  • National And Kapodistrian University of Athens
  • Centro di Thalassemia, Ospedale Civile di Lentini
  • Università di Bari - Facoltà di Medicina
  • ASL Cagliari Ospedale Regionale per le Microcitemie
  • Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi
  • Presidio Ospedaliero "Annunziata", Centro di Studi della Microcitemia
  • A.O.Universitaria Meyer
  • Clinica Pediatrica Policlinico di Modena
  • Azienda Ospedaliera di Rilievo Nazionale "Antonio Cardarelli"
  • Azienda Ospedaliera di Padova
  • Ospedali Riuniti Villa Sofia - Cervello
  • U.O.C. Ematologia - Emoglobinopatie, Ospedale G. Di Cristina
  • Clinica Pediatrica Università - ASL 1 D.H per Talassemia
  • Centre National de Greffe de Moelle Osseuse Tunis
  • Barts Health NHS Trust
  • Queen's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Deferiprone

Deferasirox

Arm Description

75-100 mg/kg/day seven days per week

20 to 40 mg/kg/day seven days per week

Outcomes

Primary Outcome Measures

Percentage of Successfully Chelated Patients
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

Liver MRI
Change in liver iron concentration (measured using liver MRI), assessed as difference between value at 12 months minus value at baseline.
Cardiac MRI T2*
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
Change in serum ferritin level, assessed as difference between value at 12 months minus value at baseline.

Full Information

First Posted
April 3, 2013
Last Updated
April 8, 2021
Sponsor
Consorzio per Valutazioni Biologiche e Farmacologiche
Collaborators
European Commission
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1. Study Identification

Unique Protocol Identification Number
NCT01825512
Brief Title
Efficacy/Safety Study of Deferiprone Compared to Deferasirox in Paediatric Patients
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
March 17, 2014 (Actual)
Primary Completion Date
September 21, 2017 (Actual)
Study Completion Date
September 21, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Consorzio per Valutazioni Biologiche e Farmacologiche
Collaborators
European Commission

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Multicentre, randomised, open label, non-inferiority active-controlled trial to evaluate efficacy and safety of a 12-months treatment with deferiprone (DFP) at dose of 75-100 mg/kg/day versus deferasirox (DFX) at dose of 20-40 mg/kg/day in paediatric patients (1 month < 18 years old) affected by hereditary haemoglobinopathies and requiring frequent transfusions and chelation.
Detailed Description
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Iron Overload
Keywords
chronic iron overload, hereditary haemoglobinopathy, beta thalassaemia major, chelating agents, deferiprone, deferasirox, children, paediatrics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
435 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Deferiprone
Arm Type
Experimental
Arm Description
75-100 mg/kg/day seven days per week
Arm Title
Deferasirox
Arm Type
Active Comparator
Arm Description
20 to 40 mg/kg/day seven days per week
Intervention Type
Drug
Intervention Name(s)
Deferiprone
Other Intervention Name(s)
DFP
Intervention Description
Deferiprone 80 mg/mL oral solution
Intervention Type
Drug
Intervention Name(s)
Deferasirox
Other Intervention Name(s)
DFX, ATC Code:V03AC03
Intervention Description
Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg
Primary Outcome Measure Information:
Title
Percentage of Successfully Chelated Patients
Description
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)
Time Frame
at baseline and after 12 months
Secondary Outcome Measure Information:
Title
Liver MRI
Description
Change in liver iron concentration (measured using liver MRI), assessed as difference between value at 12 months minus value at baseline.
Time Frame
at baseline and after 12 months
Title
Cardiac MRI T2*
Description
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.
Time Frame
at baseline and after 12 months
Title
Ferritin Level
Description
Change in serum ferritin level, assessed as difference between value at 12 months minus value at baseline.
Time Frame
at baseline and after 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Donato Bonifazi, Dr
Organizational Affiliation
Consorzio per Valutazioni Biologiche e Farmacologiche
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Aurelio Maggio, MD
Organizational Affiliation
Ospedali Riuniti Villa Sofia-Cervello
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital 'Ihsan Çabej'
City
Lushnjë
Country
Albania
Facility Name
Qendra Spitalore Universitare "Nene Tereza" Tirane
City
Tirana
Country
Albania
Facility Name
Department of Medical and Public health Services of the Ministry of Health
City
Nicosia
Country
Cyprus
Facility Name
Alexandria University Hospital - Faculty of Medicine
City
Alexandria
Country
Egypt
Facility Name
Cairo University Faculty of Medicine
City
Cairo
Country
Egypt
Facility Name
Zagazig University Hospitals
City
Zagazig
Country
Egypt
Facility Name
National And Kapodistrian University of Athens
City
Athens
Country
Greece
Facility Name
Centro di Thalassemia, Ospedale Civile di Lentini
City
Lentini
State/Province
SR
Country
Italy
Facility Name
Università di Bari - Facoltà di Medicina
City
Bari
Country
Italy
Facility Name
ASL Cagliari Ospedale Regionale per le Microcitemie
City
Cagliari
Country
Italy
Facility Name
Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi
City
Catania
Country
Italy
Facility Name
Presidio Ospedaliero "Annunziata", Centro di Studi della Microcitemia
City
Cosenza
Country
Italy
Facility Name
A.O.Universitaria Meyer
City
Firenze
Country
Italy
Facility Name
Clinica Pediatrica Policlinico di Modena
City
Modena
Country
Italy
Facility Name
Azienda Ospedaliera di Rilievo Nazionale "Antonio Cardarelli"
City
Napoli
Country
Italy
Facility Name
Azienda Ospedaliera di Padova
City
Padova
Country
Italy
Facility Name
Ospedali Riuniti Villa Sofia - Cervello
City
Palermo
Country
Italy
Facility Name
U.O.C. Ematologia - Emoglobinopatie, Ospedale G. Di Cristina
City
Palermo
Country
Italy
Facility Name
Clinica Pediatrica Università - ASL 1 D.H per Talassemia
City
Sassari
Country
Italy
Facility Name
Centre National de Greffe de Moelle Osseuse Tunis
City
Tunis
Country
Tunisia
Facility Name
Barts Health NHS Trust
City
London
Country
United Kingdom
Facility Name
Queen's Hospital
City
Romford
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33926431
Citation
Giannuzzi V, Felisi M, Bonifazi D, Devlieger H, Papanikolaou G, Ragab L, Fattoum S, Tempesta B, Reggiardo G, Ceci A. Ethical and procedural issues for applying researcher-driven multi-national paediatric clinical trials in and outside the European Union: the challenging experience of the DEEP project. BMC Med Ethics. 2021 Apr 29;22(1):49. doi: 10.1186/s12910-021-00618-2.
Results Reference
derived
PubMed Identifier
32470438
Citation
Maggio A, Kattamis A, Felisi M, Reggiardo G, El-Beshlawy A, Bejaoui M, Sherief L, Christou S, Cosmi C, Della Pasqua O, Del Vecchio GC, Filosa A, Cuccia L, Hassab H, Kreka M, Origa R, Putti MC, Spino M, Telfer P, Tempesta B, Vitrano A, Tsang YC, Zaka A, Tricta F, Bonifazi D, Ceci A. Evaluation of the efficacy and safety of deferiprone compared with deferasirox in paediatric patients with transfusion-dependent haemoglobinopathies (DEEP-2): a multicentre, randomised, open-label, non-inferiority, phase 3 trial. Lancet Haematol. 2020 Jun;7(6):e469-e478. doi: 10.1016/S2352-3026(20)30100-9.
Results Reference
derived
Links:
URL
http://www.deepproject.eu/
Description
official project website

Learn more about this trial

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

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