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

Chronic Iron Overload Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01825512
• Other study ID #: DEEP-2
• Status: Completed
• Phase: Phase 3
• Start date: March 17, 2014
• Est. completion date: September 21, 2017

Study information

• Verified date: October 2017
• Source: Consorzio per Valutazioni Biologiche e Farmacologiche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 435
• Est. completion date: September 21, 2017
• Est. primary completion date: September 21, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 17 Years

Eligibility

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 ß-HCG (Human chorionic gonadotropin) and lactating female patients

Related Conditions & MeSH terms

• Chronic Iron Overload
• Hemoglobinopathies
• Iron Overload

Intervention

Drug:
• Deferiprone
Deferiprone 80 mg/mL oral solution
• Deferasirox
Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg

Locations

Country	Name	City	State
Albania	Hospital 'Ihsan Çabej'	Lushnjë
Albania	Qendra Spitalore Universitare "Nene Tereza" Tirane	Tirana
Cyprus	Department of Medical and Public health Services of the Ministry of Health	Nicosia
Egypt	Alexandria University Hospital - Faculty of Medicine	Alexandria
Egypt	Cairo University Faculty of Medicine	Cairo
Egypt	Zagazig University Hospitals	Zagazig
Greece	National And Kapodistrian University of Athens	Athens
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	Centro di Thalassemia, Ospedale Civile di Lentini	Lentini	SR
Italy	Clinica Pediatrica Policlinico di Modena	Modena
Italy	Azienda Ospedaliera di Rilievo Nazionale "Antonio Cardarelli"	Napoli
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Ospedali Riuniti Villa Sofia - Cervello	Palermo
Italy	U.O.C. Ematologia - Emoglobinopatie, Ospedale G. Di Cristina	Palermo
Italy	Clinica Pediatrica Università - ASL 1 D.H per Talassemia	Sassari
Tunisia	Centre National de Greffe de Moelle Osseuse Tunis	Tunis
United Kingdom	Barts Health NHS Trust	London
United Kingdom	Queen's Hospital	Romford

Sponsors (2)

Lead Sponsor	Collaborator
Consorzio per Valutazioni Biologiche e Farmacologiche	European Commission

Countries where clinical trial is conducted

Albania,  Cyprus,  Egypt,  Greece,  Italy,  Tunisia,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	at baseline and after 12 months
Secondary	Liver MRI	Change in liver iron concentration (measured using liver MRI), assessed as difference between value at 12 months minus value at baseline.	at baseline and after 12 months
Secondary	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.	at baseline and after 12 months
Secondary	Ferritin Level	Change in serum ferritin level, assessed as difference between value at 12 months minus value at baseline.	at baseline and after 12 months

External Links

•   official project website