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.

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

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

Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.