Trial Outcomes & Findings for Efficacy/Safety Study of Deferiprone Compared to Deferasirox in Paediatric Patients (NCT NCT01825512)
NCT ID: NCT01825512
Last Updated: 2021-05-04
Results Overview
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)
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
435 participants
Primary outcome timeframe
at baseline and after 12 months
Results posted on
2021-05-04
Participant Flow
Informed consent was collected for 435 patients that were enrolled in the study, however 42 of them were excluded from the study for the following reasons: 17 did not meet inclusion criteria, 5 withdrew the consent and 20 were lost to follow-up.
Participant milestones
| Measure |
Deferiprone
75-100 mg/kg/day seven days per week
Deferiprone: Deferiprone 80 mg/mL oral solution
|
Deferasirox
20 to 40 mg/kg/day seven days per week
Deferasirox: Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg
|
|---|---|---|
|
Baseline
STARTED
|
194
|
199
|
|
Baseline
COMPLETED
|
193
|
197
|
|
Baseline
NOT COMPLETED
|
1
|
2
|
|
Treatment
STARTED
|
193
|
197
|
|
Treatment
COMPLETED
|
140
|
170
|
|
Treatment
NOT COMPLETED
|
53
|
27
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
The difference is due to missing data at baseline
Baseline characteristics by cohort
| Measure |
Deferiprone
n=193 Participants
75-100 mg/kg/day seven days per week
Deferiprone: Deferiprone 80 mg/mL oral solution
|
Deferasirox
n=197 Participants
20 to 40 mg/kg/day seven days per week
Deferasirox: Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg
|
Total
n=390 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
<6 years
|
59 participants
n=193 Participants
|
58 participants
n=197 Participants
|
117 participants
n=390 Participants
|
|
Age, Customized
> or equal to 6 years and <10 years
|
47 participants
n=193 Participants
|
47 participants
n=197 Participants
|
94 participants
n=390 Participants
|
|
Age, Customized
> or equal to 10 years
|
87 participants
n=193 Participants
|
92 participants
n=197 Participants
|
179 participants
n=390 Participants
|
|
Sex: Female, Male
Female
|
80 Participants
n=193 Participants
|
93 Participants
n=197 Participants
|
173 Participants
n=390 Participants
|
|
Sex: Female, Male
Male
|
113 Participants
n=193 Participants
|
104 Participants
n=197 Participants
|
217 Participants
n=390 Participants
|
|
Race/Ethnicity, Customized
Europe
|
56 participants
n=193 Participants
|
56 participants
n=197 Participants
|
112 participants
n=390 Participants
|
|
Race/Ethnicity, Customized
North Africa
|
121 participants
n=193 Participants
|
122 participants
n=197 Participants
|
243 participants
n=390 Participants
|
|
Race/Ethnicity, Customized
Rest of Africa
|
6 participants
n=193 Participants
|
5 participants
n=197 Participants
|
11 participants
n=390 Participants
|
|
Race/Ethnicity, Customized
Asia
|
0 participants
n=193 Participants
|
1 participants
n=197 Participants
|
1 participants
n=390 Participants
|
|
Race/Ethnicity, Customized
North America
|
0 participants
n=193 Participants
|
0 participants
n=197 Participants
|
0 participants
n=390 Participants
|
|
Race/Ethnicity, Customized
Latin America
|
0 participants
n=193 Participants
|
0 participants
n=197 Participants
|
0 participants
n=390 Participants
|
|
Race/Ethnicity, Customized
Other
|
5 participants
n=193 Participants
|
6 participants
n=197 Participants
|
11 participants
n=390 Participants
|
|
Race/Ethnicity, Customized
Missing
|
5 participants
n=193 Participants
|
7 participants
n=197 Participants
|
12 participants
n=390 Participants
|
|
Region of Enrollment
United Kingdom
|
11 participants
n=193 Participants
|
12 participants
n=197 Participants
|
23 participants
n=390 Participants
|
|
Region of Enrollment
Italy
|
30 participants
n=193 Participants
|
28 participants
n=197 Participants
|
58 participants
n=390 Participants
|
|
Region of Enrollment
Tunisia
|
28 participants
n=193 Participants
|
28 participants
n=197 Participants
|
56 participants
n=390 Participants
|
|
Region of Enrollment
Egypt
|
96 participants
n=193 Participants
|
99 participants
n=197 Participants
|
197 participants
n=390 Participants
|
|
Region of Enrollment
Albania
|
19 participants
n=193 Participants
|
20 participants
n=197 Participants
|
39 participants
n=390 Participants
|
|
Region of Enrollment
Greece
|
5 participants
n=193 Participants
|
6 participants
n=197 Participants
|
11 participants
n=390 Participants
|
|
Region of Enrollment
Cyprus
|
4 participants
n=193 Participants
|
4 participants
n=197 Participants
|
8 participants
n=390 Participants
|
|
Ferritin level
|
2756 ng/ml
STANDARD_DEVIATION 2175 • n=163 Participants • The difference is due to missing data at baseline
|
2989 ng/ml
STANDARD_DEVIATION 2409 • n=173 Participants • The difference is due to missing data at baseline
|
2876 ng/ml
STANDARD_DEVIATION 2298 • n=336 Participants • The difference is due to missing data at baseline
|
PRIMARY outcome
Timeframe: at baseline and after 12 monthsPopulation: Per-protocol population 1 (PP1): number of patients for whom the primary composite efficacy endpoint data were available at baseline and after 1 year of treatment (271 subjects)
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)
Outcome measures
| Measure |
Deferiprone
n=125 Participants
75-100 mg/kg/day seven days per week
Deferiprone: Deferiprone 80 mg/mL oral solution
|
Deferasirox
n=146 Participants
20 to 40 mg/kg/day seven days per week
Deferasirox: Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg
|
|---|---|---|
|
Percentage of Successfully Chelated Patients
|
69 Participants
|
80 Participants
|
SECONDARY outcome
Timeframe: at baseline and after 12 monthsPopulation: Per-protocol population 3 (PP3): number of patients for whom liver iron concentration were available at baseline and after 1 year of treatment (106 subjects)
Change in liver iron concentration (measured using liver MRI), assessed as difference between value at 12 months minus value at baseline.
Outcome measures
| Measure |
Deferiprone
n=46 Participants
75-100 mg/kg/day seven days per week
Deferiprone: Deferiprone 80 mg/mL oral solution
|
Deferasirox
n=60 Participants
20 to 40 mg/kg/day seven days per week
Deferasirox: Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg
|
|---|---|---|
|
Liver MRI
|
-0.848 mg/g
Standard Error 0.887
|
-2.975 mg/g
Standard Error 0.776
|
SECONDARY outcome
Timeframe: at baseline and after 12 monthsPopulation: Per-protocol population 3 (PP3): number of patients for whom cardiac T2\* concentration were available at baseline and after 1 year of treatment (108 subjects)
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.
Outcome measures
| Measure |
Deferiprone
n=49 Participants
75-100 mg/kg/day seven days per week
Deferiprone: Deferiprone 80 mg/mL oral solution
|
Deferasirox
n=59 Participants
20 to 40 mg/kg/day seven days per week
Deferasirox: Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg
|
|---|---|---|
|
Cardiac MRI T2*
|
0.488 milliseconds (ms)
Standard Error 1.284
|
1.121 milliseconds (ms)
Standard Error 1.169
|
SECONDARY outcome
Timeframe: at baseline and after 12 monthsPopulation: Per-protocol population 2 (PP2): number of patients for whom the per-protocol centralised serum ferritin concentration data were available at baseline and after 1 year of treatment (303 subjects, this population was larger than PP1 because PP2 included patients who did not have cardiac T2\* data)
Change in serum ferritin level, assessed as difference between value at 12 months minus value at baseline.
Outcome measures
| Measure |
Deferiprone
n=137 Participants
75-100 mg/kg/day seven days per week
Deferiprone: Deferiprone 80 mg/mL oral solution
|
Deferasirox
n=166 Participants
20 to 40 mg/kg/day seven days per week
Deferasirox: Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg
|
|---|---|---|
|
Ferritin Level
|
-397.583 ng/mL
Standard Error 121.794
|
-398.184 ng/mL
Standard Error 110.619
|
Adverse Events
Deferiprone
Serious events: 13 serious events
Other events: 152 other events
Deaths: 0 deaths
Deferasirox
Serious events: 14 serious events
Other events: 89 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Deferiprone
n=193 participants at risk
75-100 mg/kg/day seven days per week
Deferiprone: Deferiprone 80 mg/mL oral solution
|
Deferasirox
n=197 participants at risk
20 to 40 mg/kg/day seven days per week
Deferasirox: Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg
|
|---|---|---|
|
Injury, poisoning and procedural complications
testicular injury
|
0.52%
1/193 • Number of events 1 • through study completion, an average of 1 year for subject
|
0.00%
0/197 • through study completion, an average of 1 year for subject
|
|
Surgical and medical procedures
splenectomy
|
0.52%
1/193 • Number of events 1 • through study completion, an average of 1 year for subject
|
0.00%
0/197 • through study completion, an average of 1 year for subject
|
|
Blood and lymphatic system disorders
agranulocytosis
|
1.6%
3/193 • Number of events 3 • through study completion, an average of 1 year for subject
|
0.00%
0/197 • through study completion, an average of 1 year for subject
|
|
Blood and lymphatic system disorders
neutropenia
|
1.0%
2/193 • Number of events 2 • through study completion, an average of 1 year for subject
|
0.00%
0/197 • through study completion, an average of 1 year for subject
|
|
Blood and lymphatic system disorders
sickle cell anaemia with crisis subjects affected/exposed
|
0.00%
0/193 • through study completion, an average of 1 year for subject
|
1.0%
2/197 • Number of events 2 • through study completion, an average of 1 year for subject
|
|
Nervous system disorders
seizure
|
0.52%
1/193 • Number of events 1 • through study completion, an average of 1 year for subject
|
0.00%
0/197 • through study completion, an average of 1 year for subject
|
|
General disorders
pyrexia
|
0.52%
1/193 • Number of events 1 • through study completion, an average of 1 year for subject
|
0.51%
1/197 • Number of events 1 • through study completion, an average of 1 year for subject
|
|
General disorders
chest pain
|
0.00%
0/193 • through study completion, an average of 1 year for subject
|
1.0%
2/197 • Number of events 2 • through study completion, an average of 1 year for subject
|
|
General disorders
gait disturbance
|
0.00%
0/193 • through study completion, an average of 1 year for subject
|
0.51%
1/197 • Number of events 1 • through study completion, an average of 1 year for subject
|
|
Gastrointestinal disorders
diarrhoea
|
0.00%
0/193 • through study completion, an average of 1 year for subject
|
0.51%
1/197 • Number of events 1 • through study completion, an average of 1 year for subject
|
|
Hepatobiliary disorders
hypertransaminasaemia
|
1.0%
2/193 • Number of events 2 • through study completion, an average of 1 year for subject
|
0.51%
1/197 • Number of events 1 • through study completion, an average of 1 year for subject
|
|
Renal and urinary disorders
acute kidney injury
|
0.00%
0/193 • through study completion, an average of 1 year for subject
|
1.0%
2/197 • Number of events 2 • through study completion, an average of 1 year for subject
|
|
Musculoskeletal and connective tissue disorders
pain in extremity
|
0.00%
0/193 • through study completion, an average of 1 year for subject
|
0.51%
1/197 • Number of events 1 • through study completion, an average of 1 year for subject
|
|
Infections and infestations
gastroenteritis
|
0.00%
0/193 • through study completion, an average of 1 year for subject
|
0.51%
1/197 • Number of events 1 • through study completion, an average of 1 year for subject
|
|
Infections and infestations
meningitis meningococcal
|
0.00%
0/193 • through study completion, an average of 1 year for subject
|
0.51%
1/197 • Number of events 1 • through study completion, an average of 1 year for subject
|
|
Infections and infestations
herpangina
|
0.00%
0/193 • through study completion, an average of 1 year for subject
|
0.51%
1/197 • Number of events 1 • through study completion, an average of 1 year for subject
|
|
Infections and infestations
pneumonia
|
1.0%
2/193 • Number of events 2 • through study completion, an average of 1 year for subject
|
0.51%
1/197 • Number of events 1 • through study completion, an average of 1 year for subject
|
|
Infections and infestations
subcutaneous abscess
|
0.00%
0/193 • through study completion, an average of 1 year for subject
|
0.51%
1/197 • Number of events 1 • through study completion, an average of 1 year for subject
|
|
Infections and infestations
urinary tract infection
|
0.52%
1/193 • Number of events 1 • through study completion, an average of 1 year for subject
|
0.51%
1/197 • Number of events 1 • through study completion, an average of 1 year for subject
|
|
Infections and infestations
herpes virus infection
|
0.00%
0/193 • through study completion, an average of 1 year for subject
|
0.51%
1/197 • Number of events 1 • through study completion, an average of 1 year for subject
|
|
Infections and infestations
impetigo
|
0.00%
0/193 • through study completion, an average of 1 year for subject
|
0.51%
1/197 • Number of events 1 • through study completion, an average of 1 year for subject
|
|
Infections and infestations
upper respiratory tract infection
|
0.00%
0/193 • through study completion, an average of 1 year for subject
|
0.51%
1/197 • Number of events 1 • through study completion, an average of 1 year for subject
|
Other adverse events
| Measure |
Deferiprone
n=193 participants at risk
75-100 mg/kg/day seven days per week
Deferiprone: Deferiprone 80 mg/mL oral solution
|
Deferasirox
n=197 participants at risk
20 to 40 mg/kg/day seven days per week
Deferasirox: Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
cough
|
7.8%
15/193 • Number of events 21 • through study completion, an average of 1 year for subject
|
8.1%
16/197 • Number of events 25 • through study completion, an average of 1 year for subject
|
|
Blood and lymphatic system disorders
neutropenia
|
9.3%
18/193 • Number of events 26 • through study completion, an average of 1 year for subject
|
5.6%
11/197 • Number of events 15 • through study completion, an average of 1 year for subject
|
|
General disorders
pyrexia
|
14.5%
28/193 • Number of events 40 • through study completion, an average of 1 year for subject
|
16.2%
32/197 • Number of events 56 • through study completion, an average of 1 year for subject
|
|
General disorders
abdominal pain
|
10.4%
20/193 • Number of events 24 • through study completion, an average of 1 year for subject
|
4.1%
8/197 • Number of events 9 • through study completion, an average of 1 year for subject
|
|
General disorders
vomiting
|
17.1%
33/193 • Number of events 42 • through study completion, an average of 1 year for subject
|
4.1%
8/197 • Number of events 10 • through study completion, an average of 1 year for subject
|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
11.9%
23/193 • Number of events 28 • through study completion, an average of 1 year for subject
|
2.5%
5/197 • Number of events 5 • through study completion, an average of 1 year for subject
|
|
Infections and infestations
pharyngitis
|
7.8%
15/193 • Number of events 18 • through study completion, an average of 1 year for subject
|
4.6%
9/197 • Number of events 11 • through study completion, an average of 1 year for subject
|
Additional Information
Donato Bonifazi
Consorzio per Valutazioni Biologiche e Farmacologiche
Phone: +393936698076
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60