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

Primary Purpose

Thalassemia Major

Status

Completed

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

ruxolitinib

About this trial

This is an interventional treatment trial for Thalassemia Major focused on measuring thalassemia, thalassemia major, spleen enlargement, INC424, ruxolitinib

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site
Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

INC424 (ruxolitinib) - Study Treatment

Arm Description

Regularly transfused adult patients with thalassemia and spleen enlargement.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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).

Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals

Change from baseline in pre-transfusion hemoglobin levels

Percentage Change in Spleen Length (cm) Below the Left Coastal Margin

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

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.

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.

Full Information

NCT ID

NCT02049450

First Posted

January 28, 2014

Last Updated

June 19, 2017

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02049450

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2017

Overall Recruitment Status

Completed

Study Start Date

May 28, 2014 (Actual)

Primary Completion Date

April 12, 2016 (Actual)

Study Completion Date

April 12, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Thalassemia Major

Keywords

thalassemia, thalassemia major, spleen enlargement, INC424, ruxolitinib

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

INC424 (ruxolitinib) - Study Treatment

Arm Type

Experimental

Arm Description

Regularly transfused adult patients with thalassemia and spleen enlargement.

Intervention Type

Drug

Intervention Name(s)

ruxolitinib

Other Intervention Name(s)

INC424

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change of Hematocrit Adjusted Volume of Red Blood Cells (RBC)

Description

Time Frame

week 6 to week 30 interval

Secondary Outcome Measure Information:

Title

Percentage Change in Spleen Volume (cm3)

Description

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

Title

Percentage Change in Mean Pre-transfusion Hemoglobin by 6 Week Time Intervals

Description

Change from baseline in pre-transfusion hemoglobin levels

Time Frame

baseline, weeks 0 - 30

Title

Percentage Change in Spleen Length (cm) Below the Left Coastal Margin

Description

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

Title

Pharmacokinetics (PK) Parameter of Cmin

Description

Time Frame

week 2, week 12

Title

Pharmacokinetics (PK) Parameter of Cmax

Description

Time Frame

Day 1, Week 2 (Day 15), Week 12 (Day 85)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Athens

State/Province

ZIP/Postal Code

GR-115 27

Country

Greece

Facility Name

Novartis Investigative Site

City

Milano

State/Province

ZIP/Postal Code

20122

Country

Italy

Facility Name

Novartis Investigative Site

City

Palermo

State/Province

ZIP/Postal Code

90146

Country

Italy

Facility Name

Novartis Investigative Site

City

Beirut

ZIP/Postal Code

1107 2020

Country

Lebanon

Facility Name

Novartis Investigative Site

City

Bangkok

ZIP/Postal Code

10700

Country

Thailand

Facility Name

Novartis Investigative Site

City

Istanbul

ZIP/Postal Code

34093

Country

Turkey

Facility Name

Novartis Investigative Site

City

Izmir

ZIP/Postal Code

35040

Country

Turkey

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing 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

Learn more about this trial

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

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