Clinical Trial Results:
A single arm, multicenter, Phase IIa study to explore the efficacy and safety of ruxolitinib (INC424) in regularly transfused patients with thalassemia
Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results.
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Summary
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EudraCT number |
2013-002812-28 |
Trial protocol |
IT GR |
Global end of trial date |
12 Apr 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Jul 2018
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First version publication date |
19 Jul 2018
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Other versions |
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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 |
CINC424X2201
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02049450 | ||
WHO universal trial number (UTN) |
- | ||
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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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
12 Apr 2016
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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 |
12 Apr 2016
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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 |
To assess the effect of ruxolitinib on transfusion requirement.
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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 |
- | ||
Actual start date of recruitment |
28 May 2014
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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 |
Greece: 2
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Country: Number of subjects enrolled |
Italy: 5
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Country: Number of subjects enrolled |
Lebanon: 7
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Country: Number of subjects enrolled |
Thailand: 3
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Country: Number of subjects enrolled |
Turkey: 13
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Worldwide total number of subjects |
30
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EEA total number of subjects |
7
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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) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
30
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||
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Pre-assignment
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Screening details |
Approximately 30 patients were planned to be enrolled in the study. 30 patients were analyzed in the full analysis, PK, and safety sets; 27 patients were analyzed in the per-protocol set. | ||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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INC424 (ruxolitinib) - Study Treatment | ||||||||||||||
Arm description |
Regularly transfused adult patients with thalassemia and spleen enlargement | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
ruxolitinib
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Investigational medicinal product code |
INC424
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Ruxolitinib (5 mg per tablet) at a starting dose of 10 mg twice daily with dose adjustments within the range of 5 to 25 mg twice daily.
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Baseline characteristics reporting groups
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Reporting group title |
INC424 (ruxolitinib) - Study Treatment
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Reporting group description |
Regularly transfused adult patients with thalassemia and spleen enlargement | ||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
INC424 (ruxolitinib) - Study Treatment
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Reporting group description |
Regularly transfused adult patients with thalassemia and spleen enlargement | ||
Subject analysis set title |
10mg bid
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients who received INC422 10mg bid
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Subject analysis set title |
15mg bid
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients who received INC422 15mg bid
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Subject analysis set title |
20mg bid
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients who received INC422 20mg bid
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Subject analysis set title |
5mg bid
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients who received INC422 5mg bid
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End point title |
Change of hematocrit adjusted volume of red blood cells (RBC) [1] | ||||||||
End point description |
Change of RBC transfusion requirement measured as percent change of the hematocrit-adjusted volume of transfused RBC during treatment (between week 6 and week 30) compared to baseline .
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End point type |
Primary
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End point timeframe |
week 6, week 30
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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: The statistical analysis was descriptive. Mean percent change of RBC transfusion requirement was given with 95% confidence intervals: 95% CI as [-14.70, 2.83]) |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage change in spleen volume (cm3) | ||||||||||||
End point description |
Change of spleen volume from baseline at week 12 and week 30 as measured by magnetic imaging resonance (MRI) or computed tomography (CT).
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End point type |
Secondary
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End point timeframe |
baseline, week 12, week 30
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change of mean pre-transfusion hemoglobin by 6 week time intervals | ||||||||||||||||||
End point description |
Change from baseline in pre-transfusion hemoglobin levels
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End point type |
Secondary
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End point timeframe |
baseline, weeks 0 - 30
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Change in spleen length (cm) below the left coastal margin | ||||||||||||||||||||||||||
End point description |
Change of spleen length from baseline over time measured by palpitation by time
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End point type |
Secondary
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End point timeframe |
baseline, weeks 1,2,3,4,6,12,18,24,30
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| No statistical analyses for this end point | |||||||||||||||||||||||||||
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End point title |
Pharmacokinetice (PK) parameter for Cmin | ||||||||||||||||||||||||
End point description |
C min of INC424 by actual dose administered from 10mg bid to 20mg bid. Plasma PK samples were collected at Day 15 (Week 2), and Day 85 (Week 12). Cmin was collected immediately prior to dosing.
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End point type |
Secondary
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End point timeframe |
Week 2 (Day 15), Week 12 (Day 85)
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Pharmacokinetics (PK) parameter for Cmax | |||||||||||||||||||||||||||||||||||
End point description |
Cmax (1h) of INC424 by actual dose administered from 10mg bid to 20mg bid. Plasma PK samples were collected at Day 1, Week 2, and Week 12. Cmax was collected within a +/- 1 hour post dose.
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End point type |
Secondary
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End point timeframe |
Day 1, Week 2 (Day 15), Week 12 (Day 85)
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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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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
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Reporting groups
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Reporting group title |
INCB018424
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Reporting group description |
INCB018424 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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04 Dec 2014 |
Amendment 1: The purpose of this protocol amendment was:
To allow continuous use of ruxolitinib for patients who have completed 30 weeks of treatment in the study and are judged to be benefitting from study treatment according to
the investigator, and are unable to access ruxolitinib outside of this clinical trial. A treatment extension phase was introduced for the patients continuing beyond Week 30 visit
up to the time other alternatives to receive ruxolitinib from the sponsor become available; To update the contraception language to reflect current Novartis guidelines; To add some editorial clarifications and changes throughout the protocol to improve consistency and clarity. |
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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. | |||
| Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results. | |||
