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

NCT01825512 | Completed Phase 3 Results DMC

• 1 other identifier: DEEP-2
• Study Type: interventional
• Target: 435
• Locations: 7 countries
• Sites: 22

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.

Conditions

Chronic Iron Overload

Keywords

chronic iron overload; hereditary haemoglobinopathy; beta thalassaemia major; chelating agents; deferiprone; deferasirox; children; paediatrics

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Liver MRI

  at baseline and after 12 months

• Cardiac MRI T2*

  at baseline and after 12 months

• Ferritin Level

  at baseline and after 12 months

Study Arms (2)

Deferiprone

EXPERIMENTAL

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

Drug: Deferiprone

Deferasirox

ACTIVE COMPARATOR

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

Drug: Deferasirox

Interventions

Deferiprone DRUG

Deferiprone 80 mg/mL oral solution

Also known as: DFP

Deferiprone

Deferasirox DRUG

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

Also known as: DFX, ATC Code:V03AC03

Deferasirox

Eligibility Criteria

• Age: 1 Month - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Consorzio per Valutazioni Biologiche e Farmacologiche: lead
• European Commission: collaborator

Study Sites (22)

Hospital 'Ihsan Çabej'

Lushnjë, Albania

Location

Qendra Spitalore Universitare "Nene Tereza" Tirane

Tirana, Albania

Location

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

Nicosia, Cyprus

Location

Alexandria University Hospital - Faculty of Medicine

Alexandria, Egypt

Location

Cairo University Faculty of Medicine

Cairo, Egypt

Location

Zagazig University Hospitals

Zagazig, Egypt

Location

National And Kapodistrian University of Athens

Athens, Greece

Location

Centro di Thalassemia, Ospedale Civile di Lentini

Lentini, SR, Italy

Location

Università di Bari - Facoltà di Medicina

Bari, Italy

Location

ASL Cagliari Ospedale Regionale per le Microcitemie

Cagliari, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi

Catania, Italy

Location

Presidio Ospedaliero "Annunziata", Centro di Studi della Microcitemia

Cosenza, Italy

Location

A.O.Universitaria Meyer

Florence, Italy

Location

Clinica Pediatrica Policlinico di Modena

Modena, Italy

Location

Azienda Ospedaliera di Rilievo Nazionale "Antonio Cardarelli"

Napoli, Italy

Location

Azienda Ospedaliera di Padova

Padua, Italy

Location

Ospedali Riuniti Villa Sofia - Cervello

Palermo, Italy

Location

U.O.C. Ematologia - Emoglobinopatie, Ospedale G. Di Cristina

Palermo, Italy

Location

Clinica Pediatrica Università - ASL 1 D.H per Talassemia

Sassari, Italy

Location

Centre National de Greffe de Moelle Osseuse Tunis

Tunis, Tunisia

Location

Barts Health NHS Trust

London, United Kingdom

Location

Queen's Hospital

Romford, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 33926431 DERIVED

• 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.

  PMID: 32470438 DERIVED

Related Links

• official project website

MeSH Terms

Conditions

beta-Thalassemia

Interventions

Deferiprone; Isoflurophate; Deferasirox

Condition Hierarchy (Ancestors)

Thalassemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pyridones; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Organofluorophosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles

Results Point of Contact

• Title: Donato Bonifazi
• Organization: Consorzio per Valutazioni Biologiche e Farmacologiche

ceo@cvbf.net

+393936698076

Study Officials

• Donato Bonifazi, Dr

  Consorzio per Valutazioni Biologiche e Farmacologiche

  STUDY DIRECTOR

• Aurelio Maggio, MD

  Ospedali Riuniti Villa Sofia-Cervello

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2013
• First Posted: April 5, 2013
• Study Start: March 17, 2014
• Primary Completion: September 21, 2017
• Study Completion: September 21, 2017
• Last Updated: May 4, 2021
• Results First Posted: April 8, 2021

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

CY (1); TU (1); GR (1); IT (12); GB (2); EG (3); AL (2)