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 of age affected by transfusion-dependent haemoglobinopathies

• Register: EUCTR
• Last refreshed on: 21 December 2021
• Main ID: EUCTR2012-000353-31-IT
• Date of registration: 11/10/2012
• Prospective Registration: Yes
• Primary sponsor: CONSORZIO PER VALUTAZIONI BIOLOGICHE E FARMACOLOGICHE
• Public 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 of age affected by transfusion-dependent haemoglobinopathies
• 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 of age affected by transfusion-dependent haemoglobinopathies
• Date of first enrolment: 29/11/2012
• Target sample size: 344
• 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, Egypt, Greece, Italy, Tunisia, United Kingdom

Contacts

• Name: Direzione Scientifica
• Affiliation: Consorzio per le Valutazioni Biologiche e Farmacologiche

• Name: Direzione Scientifica
• Affiliation: Consorzio per le Valutazioni Biologiche e Farmacologiche

Key inclusion & exclusion criteria

Inclusion criteria:
1. 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); 2. 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; 3. For patients aged from 1 month to less than 6 years: known intolerance or contraindication to deferoxamine; 4. Written informed consent and patient's informed assent to patient’s maturity and understanding
Are the trial subjects under 18? yes
Number of subjects for this age range: 344
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 ß-HCG


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

Health Condition(s) or Problem(s) studied

Chronic iron overload
MedDRA version: 14.1 Level: LLT Classification code 10065974 Term: Chronic iron overload System Organ Class: 100000004861

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

Intervention(s)

Product Name: DEFERIPRONE
Product Code: NA
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*28CPR DISP 125MG
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 125-500

Trade Name: EXJADE*28CPR DISP 250MG
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 125-500

Trade Name: EXJADE*28CPR DISP 500MG
Pharmaceutical Form: Dispersible tablet
INN or Proposed INN: DEFERASIROX
CAS Number: 201530-41-8
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 125-500

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 relationship of demographic covariates and the disposition of DFP across the study population.

Main Objective: To assess the non-inferiority of Deferiprone compared to Deferasirox ìn terms of changes in ferritin levels and cardiac iron concentration

Primary end point(s): Percentage of successfully chelated patients assessed by serum ferritin levels (all patients) and cardiac MRI T2* (patients above 10 years of age able to have an MRI scan without sedation).

Timepoint(s) of evaluation of this end point: Serum ferritine 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)

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

Timepoint(s) of evaluation of this end point: 1. LCI 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 and 12 of treatment.

Secondary ID(s)

DEEP-2

Source(s) of Monetary Support

European Commission - HEALTH-F4-2010 - SP1 - Cooperation Collaborative Project - Grant Agreement n? 261483

Ethics review

Status: Approved
Approval date: 02/08/2012
Contact:

Results

• Results available: Yes
• Date Posted: 11/10/2019
• Date Completed: 21/09/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-000353-31/results