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NCT02049450

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

Completed Phase 2 Results posted Last updated 17 July 2017
What this trial tests

Phase 2 trial testing ruxolitinib in Thalassemia Major in 30 participants. Completed in 12 April 2016.

Timeline
28 May 2014
Primary endpoint
12 April 2016
12 April 2016

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment30
Start date28 May 2014
Primary completion12 April 2016
Estimated completion12 April 2016
Sites7 locations across Italy, Greece, Thailand, Lebanon, Turkey (Türkiye)

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Thalassemia Major. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change of Hematocrit Adjusted Volume of Red Blood Cells (RBC) Primary · week 6 to week 30 interval

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).

GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment-5.934± 22.1681
Percentage Change in Spleen Volume (cm3) Secondary · baseline, week 12, week 30

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

% change from baseline at Week 12
GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment-19.733± 16.0539
% change from baseline at Week 30
GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment-26.829± 16.6936
Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals Secondary · baseline, weeks 0 - 30

Change from baseline in pre-transfusion hemoglobin levels

Weeks 0 - 6 )
GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment0.43± 10.135
Weeks 6 - 12
GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment2.87± 10.555
Weeks 12 - 18
GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment2.78± 11.081
Weeks 18 - 24
GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment-0.56± 9.760
Weeks 24 - 30
GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment0.06± 14.321
Percentage Change in Spleen Length (cm) Below the Left Coastal Margin Secondary · baseline, weeks 1,2,3,4,6,12,18,24,30

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

Week 1
GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment-11.19± 15.376
Week 2
GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment-22.11± 23.604
Week 3
GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment-25.01± 24.178
Week 4
GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment-26.94± 25.343
Week 6
GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment-33.85± 25.251
Week 12
GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment-49.29± 26.792
Week 18
GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment-56.32± 29.994
Week 24
GroupValue95% CI
INC424 (Ruxolitinib) - Study Treatment-56.93± 29.552
Pharmacokinetics (PK) Parameter of Cmin Secondary · week 2, week 12

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.

Week 2 (Day 15)
GroupValue95% CI
10 mg Bid7.5800± 7.57959
15mg BidNA± NA
20mg BidNA± NA
Week 12 (Day 85)
GroupValue95% CI
10 mg Bid9.1300± 7.61039
15mg Bid18.5400± 23.99940
20mg Bid20.2300± 25.98617
Pharmacokinetics (PK) Parameter of Cmax Secondary · Day 1, Week 2 (Day 15), Week 12 (Day 85)

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.

Day 1
GroupValue95% CI
5mg Bid58.2000± 0.00
10mg Bid126.8000± 58.70337
15mg Bid0.00± 0.00
20mg Bid0.00± 0.00
Week 2
GroupValue95% CI
5mg Bid56.7000± 0.00
10mg Bid125.400± 40.61805
15mg Bid0.00± 0.00
20mg Bid0.00± 0.00
Week 12
GroupValue95% CI
5mg Bid0.00± 0.00
10mg Bid107.2100± 50.07525
15mg Bid245.6900± 50.00362
20mg Bid185.0000± 97.58074

Adverse events — posted to ClinicalTrials.gov

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.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

INC424 (Ruxolitinib) - Study Treatment
Serious: 6/30 (20%)
Deaths:

Serious adverse events (7 terms)

ReactionSystemINC424 (Ruxolitinib) - Stu…
PneumoniaInfections and infestations
AnaemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
Drug-induced liver injuryHepatobiliary disorders
Pneumonia viralInfections and infestations
Other adverse events (22 terms — click to expand)

ReactionSystemINC424 (Ruxolitinib) - Stu…
Upper respiratory tract infectionInfections and infestations
Abdominal pain upperGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
Weight increasedInvestigations
AnaemiaBlood and lymphatic system disorders
Alanine aminotransferase increasedInvestigations
FatigueGeneral disorders
GastroenteritisInfections and infestations
NasopharyngitisInfections and infestations
Urinary tract infectionInfections and infestations
Aspartate aminotransferase increasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
Pleuritic painRespiratory, thoracic and mediastinal disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
PyrexiaGeneral disorders
PharyngitisInfections and infestations
Increased appetiteMetabolism and nutrition disorders
MyalgiaMusculoskeletal and connective tissue disorders
Nasal congestionRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Pneumonia, Anaemia, Nausea, Vomiting, Pyrexia, Drug-induced liver injury, Pneumonia viral.

Data from ClinicalTrials.gov NCT02049450 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Erythropoiesis: insights into pathophysiology and treatments in 2017.
    Zivot A, Lipton JM, Narla A, Blanc L. · · 2018 · cited 97× · PMID 30134792 · DOI 10.1186/s10020-018-0011-z
  2. Beta Thalassemia: New Therapeutic Options Beyond Transfusion and Iron Chelation.
    Motta I, Bou-Fakhredin R, Taher AT, Cappellini MD. · · 2020 · cited 54× · PMID 32557398 · DOI 10.1007/s40265-020-01341-9
  3. Efficacy and safety of ruxolitinib in regularly transfused patients with thalassemia: results from a phase 2a study.
    Taher AT, Karakas Z, Cassinerio E, Siritanaratkul N, et al · · 2018 · cited 36× · PMID 29097381 · DOI 10.1182/blood-2017-06-790121
  4. New therapeutic targets in transfusion-dependent and -independent thalassemia.
    Cappellini MD, Motta I. · · 2017 · cited 35× · PMID 29222267 · DOI 10.1182/asheducation-2017.1.278
  5. Beyond transfusion therapy: new therapies in thalassemia including drugs, alternate donor transplant, and gene therapy.
    Porter J. · · 2018 · cited 24× · PMID 30504333 · DOI 10.1182/asheducation-2018.1.361
  6. Genomic approaches to identifying targets for treating β hemoglobinopathies.
    Ngo DA, Steinberg MH. · · 2015 · cited 19× · PMID 26215470 · DOI 10.1186/s12920-015-0120-2
  7. Innovative Treatments for Rare Anemias.
    Cappellini MD, Marcon A, Fattizzo B, Motta I. · · 2021 · cited 18× · PMID 34095760 · DOI 10.1097/hs9.0000000000000576
  8. The Roles of Mitophagy and Autophagy in Ineffective Erythropoiesis in β-Thalassemia.
    Chaichompoo P, Svasti S, Smith DR. · · 2022 · cited 16× · PMID 36142738 · DOI 10.3390/ijms231810811

Verify or expand the search:

Other trials of ruxolitinib

Trials testing the same drug.

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Other Novartis Pharmaceuticals trials

Trials by the same sponsor.

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