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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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 Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Thalassemia Major Drug: ruxolitinib Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm, Multicenter, Phase IIa Study to Explore the Efficacy and Safety of Ruxolitinib (INC424) in Regularly Transfused Patients With Thalassemia
Actual Study Start Date : May 28, 2014
Actual Primary Completion Date : April 12, 2016
Actual Study Completion Date : April 12, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Thalassemia

Arms and Interventions
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Arm Intervention/treatment
Experimental: INC424 (ruxolitinib) - Study Treatment
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.
Other Name: INC424


Outcome Measures
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Primary Outcome Measures :
  1. Change of Hematocrit Adjusted Volume of Red Blood Cells (RBC) [ Time Frame: 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).


Secondary Outcome Measures :
  1. Percentage Change in Spleen Volume (cm3) [ Time Frame: 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).

  2. Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals [ Time Frame: baseline, weeks 0 - 30 ]
    Change from baseline in pre-transfusion hemoglobin levels

  3. Percentage Change in Spleen Length (cm) Below the Left Coastal Margin [ Time Frame: baseline, weeks 1,2,3,4,6,12,18,24,30 ]
    Change of spleen length from baseline over time measured by palpitation by time

  4. Pharmacokinetics (PK) Parameter of Cmin [ Time Frame: 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.

  5. Pharmacokinetics (PK) Parameter of Cmax [ Time Frame: 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.



Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with thalassemia on a regular and stable transfusion regimen (at least 2 RBC units within every 4-week interval for 24 weeks prior to Screening) and anticipated to receive the same transfusion regimen during the study.
  • Patients with spleen enlargement at Screening, defined as spleen palpable below the costal margin and spleen volume of ≥ 450 cm3 as confirmed by MRI (or CT scan in applicable patients).
  • Patients need to be on iron chelation treatment (deferoxamine or deferasirox) for at least four weeks prior to Screening

Exclusion Criteria:

  • Splenectomy prior to or planned during the study
  • Active serious bacterial, mycobacterial, fungal, parasitic or viral infection which requires therapy (e.g., pneumonia, tuberculosis, systemic mycosis, herpes zoster)
  • Hemoglobin <65 g/L (<4.0 mmol/L) at Screening
  • Platelet count <75×109/L, absolute neutrophils count < 1.5×109/L at Screening.
  • Estimated MDRD < 30 mL/min/1.73 m2 at Screening.
  • ALT (SGPT) levels >5 times ULN at Screening.
  • Hepatocellular disease such as hepatitis B (presence of HBs antigen), hepatitis C (presence of HCV RNA), liver cirrhosis.
  • HIV positivity
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02049450


Locations
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Greece
Novartis Investigative Site
Athens, GR, Greece, GR-115 27
Italy
Novartis Investigative Site
Milano, MI, Italy, 20122
Novartis Investigative Site
Palermo, PA, Italy, 90146
Lebanon
Novartis Investigative Site
Beirut, Lebanon, 1107 2020
Thailand
Novartis Investigative Site
Bangkok, Thailand, 10700
Turkey
Novartis Investigative Site
Istanbul, Turkey, 34093
Novartis Investigative Site
Izmir, Turkey, 35040
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
More Information
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02049450    
Other Study ID Numbers: CINC424X2201
2013-002812-28 ( EudraCT Number )
First Posted: January 30, 2014    Key Record Dates
Results First Posted: June 15, 2017
Last Update Posted: July 17, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

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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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
thalassemia
thalassemia major
spleen enlargement
INC424
ruxolitinib
Additional relevant MeSH terms:
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Thalassemia
beta-Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
 Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn