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Completed

NCT Number: NCT02049450

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

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.

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Key information

Conditions

Thalassemia Major Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies Hypertrophy Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Splenomegaly Thalassemia beta-Thalassemia

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Novartis Investigative Site, Athens, GR, Greece

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Ruxolitinib

Drug

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 names: INC424

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Single Arm, Multicenter, Phase IIa Study to Explore the Efficacy and Safety of Ruxolitinib (INC424) in Regularly Transfused Patients With Thalassemia

Important dates

Study start
2014
Primary completion
2016
Study completion
2016
First posted
Jan 30, 2014
Registry last updated
Jul 17, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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