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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 )

Tracking Information
First Submitted Date  ICMJE January 28, 2014
First Posted Date  ICMJE January 30, 2014
Results First Submitted Date  ICMJE March 28, 2017
Results First Posted Date  ICMJE June 15, 2017
Last Update Posted Date July 17, 2017
Actual Study Start Date  ICMJE May 28, 2014
Actual Primary Completion Date April 12, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 19, 2017)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: January 28, 2014)
Percent change of RBC (Red Blood Cell) transfusion requirement [ Time Frame: week 6 to week 30 ]
Percent change in RBC transfusion requirement between week 6 and week 30 and the baseline period between week -24 and the day before first study drug administration.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 19, 2017)
  • 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).
  • 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
  • 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
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 28, 2014)
  • Change of spleen volume [ Time Frame: baseline, week 12, week 30 ]
    Change of spleen volume from baseline measured by MRI or CT at week 12 and week 30
  • Change of pre-transfusion hemoglobin level [ Time Frame: baseline, week 1,2,3,4,6,12,18,24,30 ]
    Change of pre-transfusion hemoglobin level from baseline at each post-baseline visit
  • Change of spleen length [ Time Frame: baseline, weeks 1,2,3,4,6,12,18,24,30 ]
    Change of spleen length from baseline over time measured by palpation
  • Pharmacokinetics (PK) parameters of Cmin and C max [ Time Frame: baseline, week 2, 12 ]
    C min and C max (1h) of INC424 by actual dose administered
  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: baseline, week 1,2,3,4,6,12,18,24,30 ]
    Adverse events (AEs), serious adverse events (SAEs), lab results, ECGs, vital signs
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Efficacy and Safety of INC424 in Regularly Transfused Patients With Thalassemia.
Official Title  ICMJE A Single Arm, Multicenter, Phase IIa Study to Explore the Efficacy and Safety of Ruxolitinib (INC424) in Regularly Transfused Patients With Thalassemia
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Thalassemia Major
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: INC424 (ruxolitinib) - Study Treatment
Regularly transfused adult patients with thalassemia and spleen enlargement.
Intervention: Drug: ruxolitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 28, 2014)
30
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 12, 2016
Actual Primary Completion Date April 12, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Greece,   Italy,   Lebanon,   Thailand,   Turkey
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02049450
Other Study ID Numbers  ICMJE CINC424X2201
2013-002812-28 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP