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

NCT ID: NCT01825512

Last Updated: 2021-05-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 435 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-17
• Study Completion Date: 2017-09-21

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).

Conditions

Chronic Iron Overload

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Deferiprone

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

Group Type: EXPERIMENTAL

Deferiprone

Intervention Type: DRUG

Deferiprone 80 mg/mL oral solution

Deferasirox

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

Group Type: ACTIVE_COMPARATOR

Deferasirox

Intervention Type: DRUG

Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg

Interventions

Deferiprone

Deferiprone 80 mg/mL oral solution

Intervention Type: DRUG

Deferasirox

Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg

Intervention Type: DRUG

Other Intervention Names

DFP; DFX; ATC Code:V03AC03

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

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Commission

OTHER

Sponsor Role: collaborator

Consorzio per Valutazioni Biologiche e Farmacologiche

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donato Bonifazi, Dr

Role: STUDY_DIRECTOR

Consorzio per Valutazioni Biologiche e Farmacologiche

Aurelio Maggio, MD

Role: PRINCIPAL_INVESTIGATOR

Ospedali Riuniti Villa Sofia-Cervello

Locations

Hospital 'Ihsan Çabej'

Lushnjë, , Albania

Qendra Spitalore Universitare "Nene Tereza" Tirane

Tirana, , Albania

Department of Medical and Public health Services of the Ministry of Health

Nicosia, , Cyprus

Alexandria University Hospital - Faculty of Medicine

Alexandria, , Egypt

Cairo University Faculty of Medicine

Cairo, , Egypt

Zagazig University Hospitals

Zagazig, , Egypt

National And Kapodistrian University of Athens

Athens, , Greece

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

Florence, , Italy

Clinica Pediatrica Policlinico di Modena

Modena, , Italy

Azienda Ospedaliera di Rilievo Nazionale "Antonio Cardarelli"

Napoli, , Italy

Azienda Ospedaliera di Padova

Padua, , 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, , Italy

Centre National de Greffe de Moelle Osseuse Tunis

Tunis, , Tunisia

Barts Health NHS Trust

London, , United Kingdom

Queen's Hospital

Romford, , United Kingdom

Countries

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

References

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.

Reference Type: DERIVED

PMID: 33926431 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32470438 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

DEEP-2

Identifier Type: -

Identifier Source: org_study_id