Clinical Trial Results:
Open-label multi-center study of Exjade (deferasirox) for treatment of transfusional iron overload in MDS, thalassemia and other anemia patients.
Summary
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EudraCT number |
2015-003531-35 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
18 May 2011
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Feb 2017
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First version publication date |
11 Feb 2017
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CICL670ARU01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01250951 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Novartis Pharma AG
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Sponsor organisation address |
CH-4002, Basel, Switzerland,
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Public contact |
Clinical Disclosure Office, Novartis Pharma AG, +41 613241111,
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Scientific contact |
Clinical Disclosure Office, Novartis Pharma AG, +41 613241111,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 May 2011
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
18 May 2011
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Primary objective was to assess the degree of reduction of the ferritin level during Exjade therapy in the patients with transfusion iron overload.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
18 May 2009
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Russian Federation: 108
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Worldwide total number of subjects |
108
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
28
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Adolescents (12-17 years) |
15
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Adults (18-64 years) |
61
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From 65 to 84 years |
4
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85 years and over |
0
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Recruitment
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Recruitment details |
Data about 3 subjects was not included in the statistical data management as it was decided by the Sponsoring Company (when these subjects were being included in the protocol) some regulations were violated. 111 subjects were enrolled but only 108 were analyzed. | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
A patient was given the study drug for the first time only when the results of the whole screening examination were obtained as well as the assessment of his correspondence to the inclusion/exclusion criteria was carried out. | ||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||
Arms
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Arm title
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Exjade | ||||||||||||||||||||||||
Arm description |
The patients were prescribed the drug in the initial dosage depending on the extent of iron overload and transfusion therapy. -The initial dosage is 30 mg/kg/ day provided that the ferritin level >2500 µg/l and more than 4 transfusions of a donor erythrocytes is received per month -The initial dosage is 10 mg/kg/day provided that the ferritin level <1500 µg/l and less than 2 transfusions of a donor erythrocytes is received per month; -The initial dosage is 20 mg/kg/day in other cases. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Deferasirox
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Investigational medicinal product code |
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Other name |
Exjade®
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Each dosage of the drug was prepared when the dispersant tablets were dissolved in a glass of water or juice (100-200ml) until a homogeneous suspension occurred. The dosage was calculated in accordance with a patient’s weight and was rounded upward to a full tablet. The drug was taken daily, 1 time a day, on an empty stomach, 30 minutes prior to a meal.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Adult group
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Adult group consisted of 65 patients the average age in this group is 59 years old.
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Subject analysis set title |
Children - 2-12 years old
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The mean age was 6.9 years old.
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Subject analysis set title |
Children - 13-17 years old
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Subject analysis set type |
Sub-group analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
In the teenage group the average age was 15 years old.
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End points reporting groups
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Reporting group title |
Exjade
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Reporting group description |
The patients were prescribed the drug in the initial dosage depending on the extent of iron overload and transfusion therapy. -The initial dosage is 30 mg/kg/ day provided that the ferritin level >2500 µg/l and more than 4 transfusions of a donor erythrocytes is received per month -The initial dosage is 10 mg/kg/day provided that the ferritin level <1500 µg/l and less than 2 transfusions of a donor erythrocytes is received per month; -The initial dosage is 20 mg/kg/day in other cases. | ||
Subject analysis set title |
Adult group
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Adult group consisted of 65 patients the average age in this group is 59 years old.
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Subject analysis set title |
Children - 2-12 years old
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
The mean age was 6.9 years old.
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Subject analysis set title |
Children - 13-17 years old
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
In the teenage group the average age was 15 years old.
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End point title |
To assess the degree of reduction of the ferritin level during Exjade therapy in the patients with transfusion iron overload. [1] | ||||||||||||||||||||||||||||||||||
End point description |
Exjade efficacy was assessed by the degree of reduction of the ferritin serum level and by the
evident manifestations of hemosiderosis of parenchymatous organs. For this reason the iron
content in liver tissue and in cardiac muscle was conducted by means of magnetic resonance
therapy once a month.
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End point type |
Primary
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End point timeframe |
From Baseline for monthly assessments for up to 1 year
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Analysis is not performed between 2 groups as this is a single arm study and combined output of all randomized patients that were analyzed. |
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Notes [2] - 3 patients were not included in the statistical data management |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
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Adverse event reporting additional description |
Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
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Reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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08 Apr 2009 |
It introduced the following changes:
• Increasing the number of patients from 60 to 150;
• Increasing the number of research centers from 7 to 20;
• Increasing the patient observation duration from 4 to 4-6 months;
• Lack of necessity to conduct all the completion procedures with the patients who have recalled their informed consent or refused to continue their participation in the trial;
• New conditions for providing the study drug to the patients in terms of providing the centers with the drug at the expense of Novartis Pharma Company during the first 6 months of the therapy. Later if a medical institution isn’t able to provide the drug, the patients continue to be observed within the protocol;
• Lowering the cases of returning of the unused drug and giving the next portion of the study drug to the patients once every 3 months instead of once a month;
• Optional mode of Visits 7-11 to the patients who have stopped taking the drug after 6 months of the trial;
• Control MRI only to the patients who have been taking the drug during the whole period of the investigation;
• Optional mode of clinical and biochemical blood and urine analyses and ferrum metabolism variables on Visits 7-11 with the patients who stopped taking the drug after 6 months of the trial;
• Optional mode of USC, ECG, EchoCG, an oculist and an otolaryngologist consultations, audiographics on the Final Visit to the patients who stopped taking the drug after 6 months of the trial.
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06 Jul 2009 |
The amendment introduced the following changes:
• Change in the expected duration of the observation of the patients from 6 to 4 months after the last center was initiated. The whole period of patients selection was 8 months (from the time when the first center was initiated);
• Addition to the inclusion criteria №2 the possibility to include patients with other rare forms of aplastic and hemolytic anemias after the Sponsor’s preliminary approval;
• Specification to the inclusion criteria №9 concerning the date when the pregnancy test should be done. Before the amendment fertile women must have done the test 7 days prior to the inclusion in the trial. After the amendment they should do the test 48 hours prior to the inclusion in the trial. Postmenopausal women must have their last menstruation not later than a year ago.
• Allowance to conduct EchoCG, X-ray examination of the thoracic cage organs, MRI, audiogram from 2 weeks during the screening examination to 6 months prior to the inclusion in the trial;
• Specification to dates when the interim Visits must be conducted (1 month ± 7 days from the date of inclusion in the protocol);
• Prolonging the final Visit to 2 weeks;
• Lack of necessity to conduct the glucose-resistance test to the patients who suffer from verified diabetes;
• Allowance to use the standard methods of the particular institution to calculate the creatinine clearance;
• In order to get the accurate results of the pregnancy tests some specification was done concerning the age categories of women patients (teenagers aged ≥ 10 y.o. with fixed menstrual cycle) and the number of negative results (there must be at least 2 negative results).
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17 Nov 2009 |
The amendment introduced the following changes:
• In accordance with the Sponsor’s decision the target number of patients must be decreased from 150 to 120;
• Shortening of the expected duration of the patients selection from 4 to 2 months after the last center was initiated in order to make it 12 months total;
• The patients should stay in the investigation and the Visits should continue even in case of the study drug has stopped being taken. Upon that the reasons for the participation completion weren’t alternated.
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |