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Study of Efficacy and Safety of INC424 in Regularly Transfused Patients With Thalassemia.

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ClinicalTrials.gov Identifier: NCT02049450
Recruitment Status : Completed
First Posted : January 30, 2014
Results First Posted : June 15, 2017
Last Update Posted : July 17, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Thalassemia Major
Intervention Drug: ruxolitinib
Enrollment 30
Recruitment Details  
Pre-assignment 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.
Arm/Group Title INC424 (Ruxolitinib) - Study Treatment
Hide Arm/Group Description Regularly transfused adult patients with thalassemia and spleen enlargement
Period Title: Overall Study
Started 30
Discontinued Treatment Prior to Week 30 4
Entered Extension Phase 18 [1]
Completed 26 [2]
Not Completed 4
Reason Not Completed
Adverse Event             2
Withdrawal by Subject             1
Patients/guardian decision             1
[1]
Of 26 who completed Core phase 18 moved into Ext. phase; All 18 eventually discontinued Ext. phase
[2]
Completed = Completed Core phase of study
Arm/Group Title INC424 (Ruxolitinib) - Study Treatment
Hide Arm/Group Description Regularly transfused adult patients with thalassemia and spleen enlargement
Overall Number of Baseline Participants 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants
25.9  (6.83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants
Female
12
  40.0%
Male
18
  60.0%
1.Primary Outcome
Title Change of Hematocrit Adjusted Volume of Red Blood Cells (RBC)
Hide Description Change of RBC transfusion requirement measured as percent change of the hematocrit-adjusted volume of transfused RBC and observed during within on-treatment interval (any time-points of RBC transfusion between week 6 and week 30 driven by the individual patient's need) compared to baseline (defined by pre-treatment interval between Week - 24 to start of treatment).
Time Frame week 6 to week 30 interval
Hide Outcome Measure Data
Hide Analysis Population Description
Per-Protocol Set (PPS) consisted of a subset of patients in the Safety Set who were compliant with requirements of the Study Protocol. Patients were excluded from the PPS if: they had no or incomplete history of RBC transfusions within 24 weeks prior to the first dose of ruxolitinib or discontinued treatment with ruxolitinib prior to Week 18.
Arm/Group Title INC424 (Ruxolitinib) - Study Treatment
Hide Arm/Group Description:
Regularly transfused adult patients with thalassemia and spleen enlargement
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: % change of hematocrit-adjusted volume
-5.934  (22.1681)
2.Secondary Outcome
Title Percentage Change in Spleen Volume (cm3)
Hide Description Change of spleen volume from baseline at week 12 and week 30 as measured by magnetic imaging resonance (MRI) or computed tomography (CT).
Time Frame baseline, week 12, week 30
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consisted of all patients who received at least one dose of ruxolitinib. All safety data was analyzed using the Safety set. The FAS and Safety set are identical in this study.
Arm/Group Title INC424 (Ruxolitinib) - Study Treatment
Hide Arm/Group Description:
Regularly transfused adult patients with thalassemia and spleen enlargement
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: percentage change
% change from baseline at Week 12 Number Analyzed 26 participants
-19.733  (16.0539)
% change from baseline at Week 30 Number Analyzed 25 participants
-26.829  (16.6936)
3.Secondary Outcome
Title Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals
Hide Description Change from baseline in pre-transfusion hemoglobin levels
Time Frame baseline, weeks 0 - 30
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consists of all patients who received at least one dose of ruxolitinib. All safety data was analyzed using the Safety set. The FAS and Safety set are identical in this study.
Arm/Group Title INC424 (Ruxolitinib) - Study Treatment
Hide Arm/Group Description:
Regularly transfused adult patients with thalassemia and spleen enlargement
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: percentage change of hemoglobin levels
Weeks 0 - 6 ) Number Analyzed 27 participants
0.43  (10.135)
Weeks 6 - 12 Number Analyzed 27 participants
2.87  (10.555)
Weeks 12 - 18 Number Analyzed 27 participants
2.78  (11.081)
Weeks 18 - 24 Number Analyzed 26 participants
-0.56  (9.760)
Weeks 24 - 30 Number Analyzed 26 participants
0.06  (14.321)
4.Secondary Outcome
Title Percentage Change in Spleen Length (cm) Below the Left Coastal Margin
Hide Description Change of spleen length from baseline over time measured by palpitation by time
Time Frame baseline, weeks 1,2,3,4,6,12,18,24,30
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Set consists of all patients who received at least one dose of ruxolitinib. All safety data was analyzed using the Safety set. The FAS and Safety set are identical in this study.
Arm/Group Title INC424 (Ruxolitinib) - Study Treatment
Hide Arm/Group Description:
Regularly transfused adult patients with thalassemia and spleen enlargement
Overall Number of Participants Analyzed 30
Mean (Standard Deviation)
Unit of Measure: percentage change in spleen length
Week 1 Number Analyzed 30 participants
-11.19  (15.376)
Week 2 Number Analyzed 30 participants
-22.11  (23.604)
Week 3 Number Analyzed 29 participants
-25.01  (24.178)
Week 4 Number Analyzed 29 participants
-26.94  (25.343)
Week 6 Number Analyzed 29 participants
-33.85  (25.251)
Week 12 Number Analyzed 29 participants
-49.29  (26.792)
Week 18 Number Analyzed 27 participants
-56.32  (29.994)
Week 24 Number Analyzed 27 participants
-56.93  (29.552)
Week 30 Number Analyzed 24 participants
-57.40  (36.970)
5.Secondary Outcome
Title Pharmacokinetics (PK) Parameter of Cmin
Hide 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. n= number of patients with valid PK samples as per definition of the PK analysis set.
Time Frame week 2, week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set includes all patients with at least one evaluable PK sample at any visit.
Arm/Group Title 10 mg Bid 15mg Bid 20mg Bid
Hide Arm/Group Description:
Patients who received INC422 10mg bid
Patients who received INC422 15mg bid
Patients who received INC422 20mg bid
Overall Number of Participants Analyzed 30 16 2
Mean (Standard Deviation)
Unit of Measure: ng/mL
Week 2 (Day 15) Number Analyzed 28 participants 16 participants 2 participants
7.5800  (7.57959) NA [1]   (NA) NA [1]   (NA)
Week 12 (Day 85) Number Analyzed 11 participants 15 participants 2 participants
9.1300  (7.61039) 18.5400  (23.99940) 20.2300  (25.98617)
[1]
N/A = per protocol, dose increase was not allowed prior to Week 6 so at week 2 no dose >10mg BID was expected
6.Secondary Outcome
Title Pharmacokinetics (PK) Parameter of Cmax
Hide 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.

n= number of patients with valid PK samples as per definition of the PK analysis set.

Time Frame Day 1, Week 2 (Day 15), Week 12 (Day 85)
Hide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set includes all patients with at least one evaluable PK sample at any visit.
Arm/Group Title 5mg Bid 10mg Bid 15mg Bid 20mg Bid
Hide Arm/Group Description:
Patients who received INC422 5mg bid
Patients who received INC422 10mg bid
Patients who received INC422 15mg bid
Patients who received INC422 20mg bid
Overall Number of Participants Analyzed 2 30 16 2
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 Number Analyzed 1 participants 29 participants 16 participants 2 participants
58.2000  (0.00) 126.8000  (58.70337) 0.00  (0.00) 0.00  (0.00)
Week 2 Number Analyzed 1 participants 28 participants 16 participants 2 participants
56.7000  (0.00) 125.400  (40.61805) 0.00  (0.00) 0.00  (0.00)
Week 12 Number Analyzed 2 participants 11 participants 16 participants 2 participants
0.00  (0.00) 107.2100  (50.07525) 245.6900  (50.00362) 185.0000  (97.58074)
Time Frame 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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title INC424 (Ruxolitinib) - Study Treatment
Hide Arm/Group Description Regularly transfused adult patients with thalassemia and spleen enlargement
All-Cause Mortality
INC424 (Ruxolitinib) - Study Treatment
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
INC424 (Ruxolitinib) - Study Treatment
Affected / at Risk (%)
Total   6/30 (20.00%) 
Blood and lymphatic system disorders   
Anaemia  1  1/30 (3.33%) 
Gastrointestinal disorders   
Nausea  1  1/30 (3.33%) 
Vomiting  1  1/30 (3.33%) 
General disorders   
Pyrexia  1  1/30 (3.33%) 
Hepatobiliary disorders   
Drug-induced liver injury  1  1/30 (3.33%) 
Infections and infestations   
Pneumonia  1  2/30 (6.67%) 
Pneumonia viral  1  1/30 (3.33%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.1)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
INC424 (Ruxolitinib) - Study Treatment
Affected / at Risk (%)
Total   23/30 (76.67%) 
Blood and lymphatic system disorders   
Anaemia  1  4/30 (13.33%) 
Gastrointestinal disorders   
Abdominal pain  1  2/30 (6.67%) 
Abdominal pain upper  1  5/30 (16.67%) 
Constipation  1  2/30 (6.67%) 
Diarrhoea  1  5/30 (16.67%) 
Nausea  1  5/30 (16.67%) 
General disorders   
Fatigue  1  3/30 (10.00%) 
Pyrexia  1  2/30 (6.67%) 
Infections and infestations   
Gastroenteritis  1  3/30 (10.00%) 
Nasopharyngitis  1  3/30 (10.00%) 
Pharyngitis  1  2/30 (6.67%) 
Upper respiratory tract infection  1  8/30 (26.67%) 
Urinary tract infection  1  3/30 (10.00%) 
Investigations   
Alanine aminotransferase increased  1  4/30 (13.33%) 
Aspartate aminotransferase increased  1  3/30 (10.00%) 
Weight increased  1  5/30 (16.67%) 
Metabolism and nutrition disorders   
Increased appetite  1  2/30 (6.67%) 
Musculoskeletal and connective tissue disorders   
Myalgia  1  2/30 (6.67%) 
Pain in extremity  1  3/30 (10.00%) 
Nervous system disorders   
Headache  1  3/30 (10.00%) 
Respiratory, thoracic and mediastinal disorders   
Nasal congestion  1  2/30 (6.67%) 
Pleuritic pain  1  3/30 (10.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: trialandresults.registries@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02049450    
Other Study ID Numbers: CINC424X2201
2013-002812-28 ( EudraCT Number )
First Submitted: January 28, 2014
First Posted: January 30, 2014
Results First Submitted: March 28, 2017
Results First Posted: June 15, 2017
Last Update Posted: July 17, 2017