Trial Outcomes & Findings for Study of Efficacy and Safety of INC424 in Regularly Transfused Patients With Thalassemia. (NCT NCT02049450)

NCT ID: NCT02049450

Last Updated: 2017-07-17

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 30 participants
• Primary outcome timeframe: week 6 to week 30 interval
• Results posted on: 2017-07-17

Participant Flow

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.

Participant milestones

Measure	INC424 (Ruxolitinib) - Study Treatment Regularly transfused adult patients with thalassemia and spleen enlargement
Overall Study STARTED	30
Overall Study Discontinued Treatment Prior to Week 30	4
Overall Study Entered Extension Phase	18
Overall Study COMPLETED	26
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure	INC424 (Ruxolitinib) - Study Treatment Regularly transfused adult patients with thalassemia and spleen enlargement
Overall Study Adverse Event	2
Overall Study Withdrawal by Subject	1
Overall Study Patients/guardian decision	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	INC424 (Ruxolitinib) - Study Treatment n=30 Participants Regularly transfused adult patients with thalassemia and spleen enlargement
Age, Continuous	25.9 years STANDARD_DEVIATION 6.83 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants

PRIMARY outcome

Timeframe: week 6 to week 30 interval

Population: 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.

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).

Outcome measures

Measure	INC424 (Ruxolitinib) - Study Treatment n=27 Participants Regularly transfused adult patients with thalassemia and spleen enlargement	15mg Bid Patients who received INC422 15mg bid	20mg Bid Patients who received INC422 20mg bid	20mg Bid Patients who received INC422 20mg bid
Change of Hematocrit Adjusted Volume of Red Blood Cells (RBC)	-5.934 % change of hematocrit-adjusted volume Standard Deviation 22.1681	—	—	—

SECONDARY outcome

Timeframe: baseline, week 12, week 30

Population: 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.

Change of spleen volume from baseline at week 12 and week 30 as measured by magnetic imaging resonance (MRI) or computed tomography (CT).

Outcome measures

Measure	INC424 (Ruxolitinib) - Study Treatment n=30 Participants Regularly transfused adult patients with thalassemia and spleen enlargement	15mg Bid Patients who received INC422 15mg bid	20mg Bid Patients who received INC422 20mg bid	20mg Bid Patients who received INC422 20mg bid
Percentage Change in Spleen Volume (cm3) % change from baseline at Week 12	-19.733 percentage change Standard Deviation 16.0539	—	—	—
Percentage Change in Spleen Volume (cm3) % change from baseline at Week 30	-26.829 percentage change Standard Deviation 16.6936	—	—	—

SECONDARY outcome

Timeframe: baseline, weeks 0 - 30

Population: 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.

Change from baseline in pre-transfusion hemoglobin levels

Outcome measures

Measure	INC424 (Ruxolitinib) - Study Treatment n=30 Participants Regularly transfused adult patients with thalassemia and spleen enlargement	15mg Bid Patients who received INC422 15mg bid	20mg Bid Patients who received INC422 20mg bid	20mg Bid Patients who received INC422 20mg bid
Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals Weeks 0 - 6 )	0.43 percentage change of hemoglobin levels Standard Deviation 10.135	—	—	—
Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals Weeks 6 - 12	2.87 percentage change of hemoglobin levels Standard Deviation 10.555	—	—	—
Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals Weeks 12 - 18	2.78 percentage change of hemoglobin levels Standard Deviation 11.081	—	—	—
Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals Weeks 18 - 24	-0.56 percentage change of hemoglobin levels Standard Deviation 9.760	—	—	—
Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals Weeks 24 - 30	0.06 percentage change of hemoglobin levels Standard Deviation 14.321	—	—	—

SECONDARY outcome

Timeframe: baseline, weeks 1,2,3,4,6,12,18,24,30

Population: 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.

Change of spleen length from baseline over time measured by palpitation by time

Outcome measures

Measure	INC424 (Ruxolitinib) - Study Treatment n=30 Participants Regularly transfused adult patients with thalassemia and spleen enlargement	15mg Bid Patients who received INC422 15mg bid	20mg Bid Patients who received INC422 20mg bid	20mg Bid Patients who received INC422 20mg bid
Percentage Change in Spleen Length (cm) Below the Left Coastal Margin Week 30	-57.40 percentage change in spleen length Standard Deviation 36.970	—	—	—
Percentage Change in Spleen Length (cm) Below the Left Coastal Margin Week 1	-11.19 percentage change in spleen length Standard Deviation 15.376	—	—	—
Percentage Change in Spleen Length (cm) Below the Left Coastal Margin Week 2	-22.11 percentage change in spleen length Standard Deviation 23.604	—	—	—
Percentage Change in Spleen Length (cm) Below the Left Coastal Margin Week 3	-25.01 percentage change in spleen length Standard Deviation 24.178	—	—	—
Percentage Change in Spleen Length (cm) Below the Left Coastal Margin Week 4	-26.94 percentage change in spleen length Standard Deviation 25.343	—	—	—
Percentage Change in Spleen Length (cm) Below the Left Coastal Margin Week 6	-33.85 percentage change in spleen length Standard Deviation 25.251	—	—	—
Percentage Change in Spleen Length (cm) Below the Left Coastal Margin Week 12	-49.29 percentage change in spleen length Standard Deviation 26.792	—	—	—
Percentage Change in Spleen Length (cm) Below the Left Coastal Margin Week 18	-56.32 percentage change in spleen length Standard Deviation 29.994	—	—	—
Percentage Change in Spleen Length (cm) Below the Left Coastal Margin Week 24	-56.93 percentage change in spleen length Standard Deviation 29.552	—	—	—

SECONDARY outcome

Timeframe: week 2, week 12

Population: The PK analysis set includes all patients with at least one evaluable PK sample at any visit.

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.

Outcome measures

Measure	INC424 (Ruxolitinib) - Study Treatment n=30 Participants Regularly transfused adult patients with thalassemia and spleen enlargement	15mg Bid n=16 Participants Patients who received INC422 15mg bid	20mg Bid n=2 Participants Patients who received INC422 20mg bid	20mg Bid Patients who received INC422 20mg bid
Pharmacokinetics (PK) Parameter of Cmin Week 2 (Day 15)	7.5800 ng/mL Standard Deviation 7.57959	NA ng/mL Standard Deviation NA N/A = per protocol, dose increase was not allowed prior to Week 6 so at week 2 no dose \>10mg BID was expected	NA ng/mL Standard Deviation NA N/A = per protocol, dose increase was not allowed prior to Week 6 so at week 2 no dose \>10mg BID was expected	—
Pharmacokinetics (PK) Parameter of Cmin Week 12 (Day 85)	9.1300 ng/mL Standard Deviation 7.61039	18.5400 ng/mL Standard Deviation 23.99940	20.2300 ng/mL Standard Deviation 25.98617	—

SECONDARY outcome

Timeframe: Day 1, Week 2 (Day 15), Week 12 (Day 85)

Population: The PK analysis set includes all patients with at least one evaluable PK sample at any visit.

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.

Outcome measures

Measure	INC424 (Ruxolitinib) - Study Treatment n=2 Participants Regularly transfused adult patients with thalassemia and spleen enlargement	15mg Bid n=30 Participants Patients who received INC422 15mg bid	20mg Bid n=16 Participants Patients who received INC422 20mg bid	20mg Bid n=2 Participants Patients who received INC422 20mg bid
Pharmacokinetics (PK) Parameter of Cmax Day 1	58.2000 ng/mL Standard Deviation 0.00	126.8000 ng/mL Standard Deviation 58.70337	0.00 ng/mL Standard Deviation 0.00	0.00 ng/mL Standard Deviation 0.00
Pharmacokinetics (PK) Parameter of Cmax Week 2	56.7000 ng/mL Standard Deviation 0.00	125.400 ng/mL Standard Deviation 40.61805	0.00 ng/mL Standard Deviation 0.00	0.00 ng/mL Standard Deviation 0.00
Pharmacokinetics (PK) Parameter of Cmax Week 12	0.00 ng/mL Standard Deviation 0.00	107.2100 ng/mL Standard Deviation 50.07525	245.6900 ng/mL Standard Deviation 50.00362	185.0000 ng/mL Standard Deviation 97.58074

Adverse Events

INC424 (Ruxolitinib) - Study Treatment

Serious events: 6 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Measure	INC424 (Ruxolitinib) - Study Treatment n=30 participants at risk Regularly transfused adult patients with thalassemia and spleen enlargement
Blood and lymphatic system disorders Anaemia	3.3% 1/30 • 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.
Gastrointestinal disorders Nausea	3.3% 1/30 • 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.
Gastrointestinal disorders Vomiting	3.3% 1/30 • 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.
General disorders Pyrexia	3.3% 1/30 • 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.
Hepatobiliary disorders Drug-induced liver injury	3.3% 1/30 • 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.
Infections and infestations Pneumonia	6.7% 2/30 • 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.
Infections and infestations Pneumonia viral	3.3% 1/30 • 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.

Other adverse events

Measure	INC424 (Ruxolitinib) - Study Treatment n=30 participants at risk Regularly transfused adult patients with thalassemia and spleen enlargement
Blood and lymphatic system disorders Anaemia	13.3% 4/30 • 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.
Gastrointestinal disorders Abdominal pain	6.7% 2/30 • 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.
Gastrointestinal disorders Abdominal pain upper	16.7% 5/30 • 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.
Gastrointestinal disorders Constipation	6.7% 2/30 • 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.
Gastrointestinal disorders Diarrhoea	16.7% 5/30 • 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.
Gastrointestinal disorders Nausea	16.7% 5/30 • 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.
General disorders Fatigue	10.0% 3/30 • 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.
General disorders Pyrexia	6.7% 2/30 • 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.
Infections and infestations Gastroenteritis	10.0% 3/30 • 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.
Infections and infestations Nasopharyngitis	10.0% 3/30 • 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.
Infections and infestations Pharyngitis	6.7% 2/30 • 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.
Infections and infestations Upper respiratory tract infection	26.7% 8/30 • 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.
Infections and infestations Urinary tract infection	10.0% 3/30 • 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.
Investigations Alanine aminotransferase increased	13.3% 4/30 • 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.
Investigations Aspartate aminotransferase increased	10.0% 3/30 • 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.
Investigations Weight increased	16.7% 5/30 • 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.
Metabolism and nutrition disorders Increased appetite	6.7% 2/30 • 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.
Musculoskeletal and connective tissue disorders Myalgia	6.7% 2/30 • 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.
Musculoskeletal and connective tissue disorders Pain in extremity	10.0% 3/30 • 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.
Nervous system disorders Headache	10.0% 3/30 • 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.
Respiratory, thoracic and mediastinal disorders Nasal congestion	6.7% 2/30 • 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.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	10.0% 3/30 • 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.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: trialandresults.registries@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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
• Publication restrictions are in place

Restriction type: OTHER