A Phase 2 interventional study of ruxolitinib in Thalassemia Major, sponsored by Novartis Pharmaceuticals. Completed at 7 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-07-17.
Sponsored by Novartis Pharmaceuticals · Phase 2, Interventional, and Treatment
Patients with severe thalassemia (thalassemia major) present with severe anemia that required life-long transfusion therapy, spleen enlargement that led to increased transfusion requirement, and other serious complications as early death, growth retardation, bone deformations and iron overload due to blood transfusions. Splenectomy can significantly reduce transfusion requirement in thalassemia patients, but it is associated with an increased risk of serious complications such as sepsis and thrombosis. Preliminary preclinical and clinical data suggested that JAK2 inhibition, by reducing spleen size, could improve hemoglobin levels, thereby eliminating the need for splenectomy and reducing transfusion requirement and related iron overload.
416 studies on the registry are indexed under Thalassemia; 67 are open to participants now.
This study's enrollment of 30 is below the median of 37 across 277 interventional studies indexed under Thalassemia.
Browse Thalassemia studies →Novartis Pharmaceuticals is the lead sponsor of 2,673 studies on the registry; 228 are open to participants now.
Of its 576 completed or terminated interventional studies of FDA-regulated products, 431 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Regularly transfused adult patients with thalassemia and spleen enlargement.
Drug: ruxolitinib
Ruxolitinib was taken at a starting dose of 10 mg twice daily with dose adjustments within the range of 5 to 25 mg twice daily.
Also known as: INC424
Change of Hematocrit Adjusted Volume of Red Blood Cells (RBC)
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
Percentage Change in Spleen Volume (cm3)
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
Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals
Change from baseline in pre-transfusion hemoglobin levels
Time frame: baseline, weeks 0 - 30
Percentage Change in Spleen Length (cm) Below the Left Coastal Margin
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
Pharmacokinetics (PK) Parameter of Cmin
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
Pharmacokinetics (PK) Parameter of Cmax
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)
| Milestone | INC424 (Ruxolitinib) - Study Treatment |
|---|---|
| Started | 30 |
| Discontinued treatment prior to week 30 | 4 |
| Entered extension phase | 18 |
| Completed | 26 |
| Not completed | 4 |
| Withdrew: Adverse event | 2 |
| Withdrew: Withdrawal by subject | 1 |
| Withdrew: Patients/guardian decision | 1 |
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).
| % change of hematocrit-adjusted volume | INC424 (Ruxolitinib) - Study Treatment |
|---|---|
| Change of Hematocrit Adjusted Volume of Red Blood Cells (RBC) | -5.934 ± 22.1681 |
Change of spleen volume from baseline at week 12 and week 30 as measured by magnetic imaging resonance (MRI) or computed tomography (CT).
| percentage change | INC424 (Ruxolitinib) - Study Treatment |
|---|---|
| % change from baseline at Week 12 | -19.733 ± 16.0539 |
| % change from baseline at Week 30 | -26.829 ± 16.6936 |
Change from baseline in pre-transfusion hemoglobin levels
| percentage change of hemoglobin levels | INC424 (Ruxolitinib) - Study Treatment |
|---|---|
| Weeks 0 - 6 ) | 0.43 ± 10.135 |
| Weeks 6 - 12 | 2.87 ± 10.555 |
| Weeks 12 - 18 | 2.78 ± 11.081 |
| Weeks 18 - 24 | -0.56 ± 9.760 |
| Weeks 24 - 30 | 0.06 ± 14.321 |
Change of spleen length from baseline over time measured by palpitation by time
| percentage change in spleen length | INC424 (Ruxolitinib) - Study Treatment |
|---|---|
| Week 1 | -11.19 ± 15.376 |
| Week 2 | -22.11 ± 23.604 |
| Week 3 | -25.01 ± 24.178 |
| Week 4 | -26.94 ± 25.343 |
| Week 6 | -33.85 ± 25.251 |
| Week 12 | -49.29 ± 26.792 |
| Week 18 | -56.32 ± 29.994 |
| Week 24 | -56.93 ± 29.552 |
| Week 30 | -57.40 ± 36.970 |
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.
| ng/mL | 10 mg Bid | 15mg Bid | 20mg Bid |
|---|---|---|---|
| Week 2 (Day 15) | 7.5800 ± 7.57959 | NA ± NA | NA ± NA |
| Week 12 (Day 85) | 9.1300 ± 7.61039 | 18.5400 ± 23.99940 | 20.2300 ± 25.98617 |
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.
| ng/mL | 5mg Bid | 10mg Bid | 15mg Bid | 20mg Bid |
|---|---|---|---|---|
| Day 1 | 58.2000 ± 0.00 | 126.8000 ± 58.70337 | 0.00 ± 0.00 | 0.00 ± 0.00 |
| Week 2 | 56.7000 ± 0.00 | 125.400 ± 40.61805 | 0.00 ± 0.00 | 0.00 ± 0.00 |
| Week 12 | 0.00 ± 0.00 | 107.2100 ± 50.07525 | 245.6900 ± 50.00362 | 185.0000 ± 97.58074 |
Collected over 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.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| INC424 (Ruxolitinib) - Study Treatment | — | 6/30 (20%) | 23/30 (76.7%) |
| Event | INC424 (Ruxolitinib) - Study Treatment |
|---|---|
| PneumoniaInfections and infestations | 2/30 |
| AnaemiaBlood and lymphatic system disorders | 1/30 |
| NauseaGastrointestinal disorders | 1/30 |
| VomitingGastrointestinal disorders | 1/30 |
| PyrexiaGeneral disorders | 1/30 |
| Drug-induced liver injuryHepatobiliary disorders | 1/30 |
| Pneumonia viralInfections and infestations | 1/30 |
| Event | INC424 (Ruxolitinib) - Study Treatment |
|---|---|
| Upper respiratory tract infectionInfections and infestations | 8/30 |
| Abdominal pain upperGastrointestinal disorders | 5/30 |
| DiarrhoeaGastrointestinal disorders | 5/30 |
| NauseaGastrointestinal disorders | 5/30 |
| Weight increasedInvestigations | 5/30 |
| AnaemiaBlood and lymphatic system disorders | 4/30 |
| Alanine aminotransferase increasedInvestigations | 4/30 |
| FatigueGeneral disorders | 3/30 |
| GastroenteritisInfections and infestations | 3/30 |
| NasopharyngitisInfections and infestations | 3/30 |
| Age, Continuous(years) | INC424 (Ruxolitinib) - Study Treatment |
|---|---|
| Mean | 25.9 ± 6.83 |
| Sex: Female, Male(Participants) | INC424 (Ruxolitinib) - Study Treatment |
|---|---|
| Female | 12 |
| Male | 18 |
Plan to share: Undecided — Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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