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

Thalassemia Major Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02049450
• Other study ID #: CINC424X2201
• Status: Completed
• Phase: Phase 2
• First received: January 28, 2014
• Last updated: May 4, 2016
• Start date: May 2014
• Est. completion date: April 2016

Study information

• Verified date: May 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Turkey: Ministry of HealthLebanon: Ministry of Public HealthItaly: The Italian Medicines AgencyGreece: Ministry of Health and Welfare
• Study type: Interventional

Clinical Trial Summary

Patients with severe thalassemia (thalassemia major) present with severe anemia that requires life-long transfusion therapy, spleen enlargement that may lead 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 suggest that JAK2 inhibition, by reducing spleen size, may improve hemoglobin levels, thereby eliminating the need for splenectomy and reducing transfusion requirement and related iron overload.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients 18 years of age or older

2. 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.

3. 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).

4. Patients need to be on iron chelation treatment (deferoxamine or deferasirox) for at least four weeks prior to Screening

Exclusion Criteria:

1. Splenectomy prior to or planned during the study.

2. Active serious bacterial, mycobacterial, fungal, parasitic or viral infection which requires therapy (e.g., pneumonia, tuberculosis, systemic mycosis, herpes zoster).

3. Hemoglobin <65 g/L (<4.0 mmol/L) at Screening.

4. Platelet count <75×109/L, absolute neutrophils count < 1.5×109/L at Screening.

5. Estimated MDRD < 30 mL/min/1.73 m2 at Screening.

6. ALT (SGPT) levels >5 times ULN at Screening.

7. Hepatocellular disease such as hepatitis B (presence of HBs antigen), hepatitis C (presence of HCV RNA), liver cirrhosis.

8. HIV positivity

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Beta-Thalassemia
• Thalassemia
• Thalassemia Major

Intervention

Drug:
• INC424 (ruxolitinib)
INC424 oral tablet (5 miligrams)

Locations

Country	Name	City	State
Greece	Novartis Investigative Site	Athens	GR
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Palermo	PA
Lebanon	Novartis Investigative Site	Beirut
Thailand	Novartis Investigative Site	Bangkok
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Izmir

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Greece,  Italy,  Lebanon,  Thailand,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent change of RBC (Red Blood Cell) transfusion requirement	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.	week 6 to week 30	No
Secondary	Change of spleen volume	Change of spleen volume from baseline measured by MRI or CT at week 12 and week 30	baseline, week 12, week 30	No
Secondary	Change of pre-transfusion hemoglobin level	Change of pre-transfusion hemoglobin level from baseline at each post-baseline visit	baseline, week 1,2,3,4,6,12,18,24,30	No
Secondary	Change of spleen length	Change of spleen length from baseline over time measured by palpation	baseline, week 1,2,3,4,6,12,18,24,30	No
Secondary	Pharmacokinetics (PK) parameters of Cmin and C max	C min and C max (1h) of INC424 by actual dose administered	baseline, week 2, 12	No
Secondary	Number of participants with adverse events as a measure of safety and tolerability	Adverse events (AEs), serious adverse events (SAEs), lab results, ECGs, vital signs	baseline, week 1,2,3,4,6,12,18,24,30	Yes