Phase 2 Study in Japanese Patients With Intermediate-2 or High Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly

• Status: Completed
• Trial end date: 2014-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary Objective:

• To evaluate the efficacy of daily oral doses of 300 mg, 400 mg, and 500 mg SAR302503 and combined for the response rate defined with the ≥35% reduction of spleen volume as determined by magnetic resonance imaging (MRI or computed tomography scan [CT] in patients with contraindications for MRI).

Secondary Objectives:

• To evaluate the safety of SAR302503 for both pooled (300, 400, and 500mg) and individual doses population.

• To evaluate the pharmacokinetics (PK) of SAR302503 after single and repeat-dose.

• To evaluate the effect on Myelofibrosis (MF)-associated symptoms (Key MF symptoms) as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF).

• To evaluate the durability of splenic response.

• To evaluate the effect of SAR302503 on bone marrow with regard to changes on reticulin fibrosis.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Sanofi

Criteria

Inclusion criteria :

• Diagnosis of primary or post-polycythemia vera or post-essential thrombocythemia myelofibrosis

• Myelofibrosis classified as high-risk or intermediate-risk level 2

• Enlarged spleen, palpable at least 5 cm below costal margin

• Active symptoms of myelofibrosis

• At least 20 years of age

• Eastern Collaborative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 at study entry

• Absence of active malignancy other than myelofibrosis

• Written informed consent to participate.

Exclusion criteria:

• Splenectomy.

• Any recent chemotherapy (eg, hydroxyurea), immunomodulatory drug therapy (eg, thalidomide, interferon-alpha), immunosuppressive therapy, corticosteroids >10 mg/day prednisone or equivalent, or growth factor treatment (eg, erythropoietin), hormones (eg, androgens, danazol) within 14 days prior to initiation of study drug.

• Major surgery therapy within 28 days or radiation including spleen radiation within 6 months prior to initiation of study drug.

• Concomitant treatment with or use of pharmaceutical or herbal agents known to be moderate or severe inhibitors or inducers CYP3A4.

• Active acute infection requiring antibiotics.

• Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug.

• Participation in any study of an investigational agent (drug, biologic, device) within 30 days, unless during nontreatment phase.

• Prior treatment with a JAK 2 Inhibitor.

• Treatment with aspirin in doses >150 mg/day

• Known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness.

• Pregnant or lactating female. Once the lactating female stop and participate in the study, she cannot re-start feeding the baby.

• Women of childbearing potential, unless using effective contraception while on study drug. Otherwise patients must be post-menopausal (at least 1 years from last menstruation without other medical reason), or surgically sterile.

• Known active (acute or chronic) Hepatitis A, B, or C; and hepatitis B and C carriers.

• Prior history of chronic liver disease (eg, chronic alcoholic liver disease, autoimmune hepatitis, sclerosing cholangitis, primary biliary cirrhosis, hemachromatosis, non-alcoholic steatohepatitis [NASH])

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.