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.
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
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
Show all 14Show fewer
- 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.
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
Egypt3 sites
Alexandria University Hospital - Faculty of Medicine
Alexandria
Cairo University Faculty of Medicine
Cairo
Zagazig University Hospitals
Zagazig
Albania2 sites
Hospital 'Ihsan Çabej'
Lushnje
Qendra Spitalore Universitare "Nene Tereza" Tirane
Tirana
United Kingdom2 sites
Barts Health NHS Trust
London
Queen's Hospital
Romford
Cyprus1 site
Department of Medical and Public health Services of the Ministry of Health
Nicosia
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
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.
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 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.
- 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)
Sponsor and investigators
- Lead sponsor
- Consorzio per Valutazioni Biologiche e Farmacologiche
- Sponsor type
- University, hospital or other
- Collaborators
- European Commission
- Responsible party
- Sponsor
- Investigators
- Donato Bonifazi, Dr, Study director, Consorzio per Valutazioni Biologiche e FarmacologicheAurelio Maggio, MD, Principal investigator, Ospedali Riuniti Villa Sofia-Cervello
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 33926431Maggio 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
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01825512
- Acronym / sponsor ID
- DEEP-2
- Conditions
- Chronic Iron Overload
- Keywords
- chronic iron overload, hereditary haemoglobinopathy, beta thalassaemia major, chelating agents, deferiprone, deferasirox, children, paediatrics
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 435 participants (actual)
- Lead sponsor
- Consorzio per Valutazioni Biologiche e FarmacologicheUniversity, hospital or other
- Collaborators
- European Commission
- Study start
- 17 Mar 2014 (actual)
- Primary completion
- 21 Sep 2017 (actual)
- Study completion
- 21 Sep 2017 (actual)
- First posted
- 5 Apr 2013 (estimated)
- Results
- Posted 8 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Deferiprone | Experimental | Drug: Deferiprone75-100 mg/kg/day seven days per week |
| Deferasirox | Active comparator | Drug: Deferasirox20 to 40 mg/kg/day seven days per week |
Who may qualify
- Ages
- 1 month to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DeferiproneAlso: DFPDeferiprone 80 mg/mL oral solution | Drug | Deferiprone |
| DeferasiroxAlso: DFX, ATC Code:V03AC03Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg | Drug | Deferasirox |
Primary outcome
Percentage of Successfully Chelated Patients
Time frame: at baseline and after 12 months
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)
3 secondary outcomes
Liver MRI
Time frame: at baseline and after 12 months
Cardiac MRI T2*
Time frame: at baseline and after 12 months
Ferritin Level
Time frame: at baseline and after 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33926431Giannuzzi 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.
- Derived from this study: PubMed 32470438Maggio 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.
- official project websiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donato Bonifazi, Dr study director
Consorzio per Valutazioni Biologiche e Farmacologiche
Aurelio Maggio, MD principal investigator
Ospedali Riuniti Villa Sofia-Cervello
22 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in Italy, Egypt, Albania, United Kingdom, Cyprus and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Successfully Chelated Patients (time frame: at baseline and after 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01825512, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2021.