Chronic Iron OverloadPhase 3NCT01825512

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

A Phase 3 study testing Deferiprone and Deferasirox in people with Chronic Iron Overload, run by Consorzio per Valutazioni Biologiche e Farmacologiche at 22 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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… Read more about this study

Who is it for?: Ages 1 month to 17 years
Conditions the study is for: Chronic Iron Overload
What is being tested?: Deferiprone and Deferasirox
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 435 participants
Where: 22 sitesin 7 countries
Study dates: 17 Mar 2014to 21 Sep 2017
Phase: Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 1 month to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

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

Who cannot join

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

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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

Trial locations and contacts

22 sites in 7 countries.

Country

City, postcode or hospital

22 sites in 7 countries

Italy12 sites

Università di Bari - Facoltà di Medicina
Bari
ASL Cagliari Ospedale Regionale per le Microcitemie
Cagliari
Azienda Ospedaliera di Rilievo Nazionale e di Alta Specializzazione Garibaldi
Catania
Presidio Ospedaliero "Annunziata", Centro di Studi della Microcitemia
Cosenza
A.O.Universitaria Meyer
Florence
Centro di Thalassemia, Ospedale Civile di Lentini
Lentini, SR
Clinica Pediatrica Policlinico di Modena
Modena
Azienda Ospedaliera di Rilievo Nazionale "Antonio Cardarelli"
Naples
Azienda Ospedaliera di Padova
Padova
Ospedali Riuniti Villa Sofia - Cervello
Palermo
U.O.C. Ematologia - Emoglobinopatie, Ospedale G. Di Cristina
Palermo
Clinica Pediatrica Università - ASL 1 D.H per Talassemia
Sassari

Other trials in Italy

Egypt3 sites

Alexandria University Hospital - Faculty of Medicine
Alexandria
Cairo University Faculty of Medicine
Cairo
Zagazig University Hospitals
Zagazig

Other trials in Egypt

Albania2 sites

Hospital 'Ihsan Çabej'
Lushnje
Qendra Spitalore Universitare "Nene Tereza" Tirane
Tirana

Other trials in Albania

United Kingdom2 sites

Barts Health NHS Trust
London
Queen's Hospital
Romford

Other trials in United Kingdom

Cyprus1 site

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

Other trials in Cyprus

Greece1 site

National And Kapodistrian University of Athens
Athens

Other trials in Greece

Tunisia1 site

Centre National de Greffe de Moelle Osseuse Tunis
Tunis

Other trials in Tunisia

About this study

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

Read the 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
Being tested: Deferiprone, Deferasirox
Keywords: chronic iron overload, hereditary haemoglobinopathy, beta thalassaemia major, chelating agents, deferiprone, deferasirox, children, paediatrics
Medical subject headings: beta-Thalassemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DeferiproneDrug
Also called DFP
Deferiprone 80 mg/mL oral solution
DeferasiroxDrug
Also called DFX, ATC Code:V03AC03
Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg

Study groups in NCT01825512
Study group	Role	What they receive
Deferiprone	Experimental	75-100 mg/kg/day seven days per week Receives: Drug: Deferiprone
Deferasirox	Active comparator	20 to 40 mg/kg/day seven days per week Receives: Drug: Deferasirox

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
Measured: at baseline and after 12 months

Secondary outcomes (3)

Liver MRI
Change in liver iron concentration (measured using liver MRI), assessed as difference between value at 12 months minus value at baseline.
Measured: at baseline and after 12 months
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.
Measured: at baseline and after 12 months
Ferritin Level
Change in serum ferritin level, assessed as difference between value at 12 months minus value at baseline.
Measured: at baseline and after 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 Mar 201421 Sep 2017

First posted5 Apr 2013 (estimated)
Study start17 Mar 2014
Primary completion21 Sep 2017
Study completion21 Sep 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Chronic Iron OverloadStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 435 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01825512
Sponsor's protocol ID: DEEP-2
Status last verified: Oct 2017
First submitted: 3 Apr 2013
Last updated: 4 May 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Publications

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.
PubMed 33926431
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.
PubMed 32470438