Efficacy and safety study to compare deferiprone versus deferasirox in paediatric patients

• Register: EUCTR
• Last refreshed on: 10 September 2018
• Main ID: EUCTR2012-000353-31-GB
• Date of registration: 26/08/2014
• Prospective Registration: Yes
• Primary sponsor: Consorzio per Valutazioni Biologiche e Farmacologiche
• Public title: Efficacy and safety study to compare deferiprone versus deferasirox in paediatric patients
• Scientific title: Multicentre, randomised, open label, non-inferiority active-controlled trial to evaluate the efficacy and safety of deferiprone compared to deferasirox in paediatric patients aged from 1 month to less than 18 years affected by transfusion-dependent haemoglobinopathies - DEferiprone Evaluation in Paediatrics
• Date of first enrolment: 26/01/2015
• Target sample size: 388
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000353-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Albania, Cyprus, Egypt, Greece, Italy, Lebanon, Morocco, Qatar, Tunisia, Turkey, United Kingdom

Contacts

• Name: DEEP-2 Trial Management Team
• Affiliation: Consorzio per Valutazioni Biologiche e Farmacologiche

• Name: DEEP-2 Trial Management Team
• Affiliation: Consorzio per Valutazioni Biologiche e Farmacologiche

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients of both genders aged from 1 month up to less than 18 years at the time of enrolment;
2. Patients affected by any hereditary haemoglobinopathy requiring chronic transfusion therapy and chelation, including but not limited to thalassemia syndromes and sickle cell disease;
3. Patients on current treatment with 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);
4. 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;
5. Until availability of results from the PK study (study DEEP-1, EudraCT no. 2012-000658-67) for patients aged from 1 month to less than 6 years: known intolerance or contraindication to deferoxamine;
6. Written informed consent and patient's informed assent according to patient?'s maturity and understanding.
Are the trial subjects under 18? yes
Number of subjects for this age range: 388
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion criteria:
1. Patients with known intolerance or contraindication to either DFP or DFX;
2. Patients receiving DFX at a dose > 40 mg/kg/day or DFP at a dose > 100 mg/kg/day at screening;
3. Platelet count <100.000/mm3 during the run-in phase;
4. Absolute neutrophils count <1.500/mm3 during the run-in phase;
5. Hb levels lower than 8g/dL during the run-in phase;
6. Evidence of abnormal liver function;
7. Iron overload from causes other than trasfusional haemosiderosis;
8. Severe heart dysfunction secondary to iron overload;
9. Serum creatinine level > ULN for age during the run-in phase;
10. History of significant medical or psychiatric disorder;
11. The patient has received another investigational drug within 30 days prior to this study;
12. Fever and other signs/symptoms of infection in the 10 days before baseline assessment;
13. Concomitant use of trivalent cation-dependent medicinal products such as aluminium-based antacids;
14. Positive test for beta-HCG or lactating female patients.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

chronic iron overload
MedDRA version: 20.0 Level: LLT Classification code 10065974 Term: Chronic iron overload System Organ Class: 100000019570

Intervention(s)

Product Name: DEFERIPRONE
Pharmaceutical Form: Oral solution
INN or Proposed INN: DEFERIPRONE
CAS Number: 30652-11-0
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 80-

Trade Name: EXJADE
Product Name: DEFERASIROX
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 125-

Trade Name: EXJADE
Product Name: DEFERASIROX
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Trade Name: EXJADE
Product Name: DEFERASIROX
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Secondary Objective: 1. To assess treatment efficacy in terms of ferritin levels;
2. To assess treatment efficacy in terms of cardiac MRI T2* in patients over 10 years of age able to perform MRI scan without sedation;
3. To estimate the efficacy of treatments in terms of liver iron concentration (LIC) measured by MRI in all paediatric subjects able to have MRI scan without sedation;
4. To evaluate the safety and tolerability profile of treatments;
5. To assess healthcare resources utilisation and patient global assessment, including compliance and quality of life evaluation;
6. To confirm the influence of demographic covariates on the pharmacokinetic disposition of treatments across the study population.

Primary end point(s): The percentage of patients successfully chelated is 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).

In details, a composite outcome measure will be defined as primary endpoint of the study according to patient’s age, as follows:
• in patients < 10 years of age treatment success will be defined only in terms of serum ferritin level (criterion A);
• in patients = 10 years of age treatment success will be defined in terms of both serum ferritin level and cardiac MRI T2* (criteria A and B).
In patients =10 years of age who would require sedation for the MRI scan, treatment success will be defined only in terms of serum ferritin level (criterion A).

Main Objective: To assess the non-inferiority of deferiprone compared to deferasirox ìn terms of changes in ferritin levels and cardiac iron concentration in paediatric patients affected by hereditary haemoglobinopaties requiring chronic transfusions and chelation.

Timepoint(s) of evaluation of this end point: Serum ferritin will be measured every 3 months; Cardiac MRI (Magnetic Resonance Imaging) T2* will be measured at month 1, 6 and 12 of treatment. Primary endpoint in terms of percentage of successfully chelated patients will be assessed as difference between basal and final
(12 months) levels.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. LIC will be assessed at baseline and at the end of treatment (12 months);
2. Adverse events (nature, severity, grade, duration) will be recorded monthly;
3. Quality of Life will be assessed at month 1, at month 6 and at month 12 of treatment;
4. Steady state concentration will be evaluated at month 12 of treatment.

Secondary end point(s): 1. Liver Iron Concentration (LlC) as measured by MRI (Magnetic Resonance Imaging) in patients able to undergo MRI scan without sedation;
2. Safety and tolerability assessments;
3. Quality of Life;
4. Steady state concentration.

Secondary ID(s)

DEEP-2

NCT01825512

2012-000353-31-IT

Source(s) of Monetary Support

European Commission HEALTH-F4-2010 SP1 - GA 261483