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

Novartis

Status and phase: Completed; Phase 2

Conditions: Thalassemia Major

Treatments: Drug: ruxolitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT02049450

2013-002812-28 (EudraCT Number)

CINC424X2201

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

INC424 (ruxolitinib) - Study Treatment

Experimental group

Description:

Regularly transfused adult patients with thalassemia and spleen enlargement.

Treatment:

Drug: ruxolitinib