Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis (JAKARTA)

Tracking Information
First Submitted Date ICMJE	September 16, 2011
First Posted Date ICMJE	September 21, 2011
Last Update Posted Date	January 8, 2016
Study Start Date ICMJE	December 2011
Actual Primary Completion Date	June 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: September 20, 2011)	Response Rate (RR), defined as the proportion of patients who have a ≥35% reduction in volume of spleen size at the end of Cycle 6, and confirmed 4 weeks thereafter [ Time Frame: 6 months ]
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01437787 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: January 25, 2013)	Symptom Response Rate (SRR): Proportion of patients with ≥50% reduction from baseline to the end of Cycle 6 in the total symptom score. [ Time Frame: 6 months ]This assessment will be conducted through the modified MFSAF diary, which will be completed during the week prior to Day 1 of each treatment cycle up to Cycle 6, and during the week prior to the end of Cycle 6.; OS (overall survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo. [ Time Frame: approximately 5 years ]; PFS (progression free survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo. [ Time Frame: approximately 5 years ]; Proportion of patients who have ≥25% reduction in volume of spleen size at end of Cycle 6, and confirmed 4 weeks thereafter. [ Time Frame: 6 months ]; Duration of spleen response, measured by MRI (or CT scan in patients with contraindications for MRI. [ Time Frame: 2 years ]; Clinical and laboratory events graded by the NCI CTCAE v4.03. [ Time Frame: approximately 5 years ]
Original Secondary Outcome Measures ICMJE; (submitted: September 20, 2011)	Symptom Response Rate (SRR): Proportion of patients with ≥50% reduction from baseline to the end of Cycle 6 in the total symptom score. [ Time Frame: 6 months ]This assessment will be conducted through the modified MFSAF diary, which will be completed during the week prior to Day 1 of each treatment cycle up to Cycle 6, at end of Cycle 6, the EOT visit, and the 30-day follow-up visit.; OS (overall survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo. [ Time Frame: approximately 5 years ]; PFS (progression free survival) of either 400 mg/day or 500 mg/day of IMP as compared to placebo. [ Time Frame: approximately 5 years ]; Proportion of patients who have ≥25% reduction in volume of spleen size at end of Cycle 6, and confirmed 4 weeks thereafter. [ Time Frame: 6 months ]; Duration of spleen response, measured by MRI (or CT scan in patients with contraindications for MRI. [ Time Frame: 2 years ]; Clinical and laboratory events graded by the NCI CTCAE v4.03. [ Time Frame: approximately 5 years ]Safety, as assessed by clinical, laboratory, ECG, and vital sign events; graded by the NCI CTCAE v4.03
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis
Official Title ICMJE	A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Study of SAR302503 in Patients With Intermediate-2 or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly
Brief Summary	Primary Objective: To evaluate the efficacy of daily oral doses of 400 mg or 500 mg of SAR302503 (Investigational Medicinal Product, IMP) compared to placebo in the reduction of spleen volume as determined by magnetic resonance imaging (MRI) (or computed tomography scan in patients with contraindications for MRI). Secondary Objectives: To evaluate the effect on Myelofibrosis (MF)-associated symptoms (key MF symptoms) as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) diary.; To evaluate the Overall Survival of patients treated with either 400 mg/day or 500 mg/day of IMP as compared to placebo.; To evaluate the Progression Free Survival of patients treated with either 400 mg/day or 500 mg/day of IMP as compared to placebo.; To evaluate the durability of splenic response.; To evaluate the safety of IMP.
Detailed Description	The expected duration of a patient's treatment in this study is approximately 8 months, based on a maximum 28-day screening period, followed by a ≥6-month (6-cycle) treatment period, and an End Of Treatment (EOT) visit, which should be performed at least 30 days following the last administration of IMP or placebo. Patients who continue to benefit clinically will be allowed to remain on IMP or placebo beyond the 6-month treatment period until the occurrence of disease progression or unacceptable toxicity.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition ICMJE	Hematopoietic Neoplasm
Intervention ICMJE	Drug: SAR302503 Pharmaceutical form:capsule Route of administration: oral; Drug: Placebo Pharmaceutical form:capsule Route of administration: oral
Study Arms	Placebo Comparator: Placebo comparator once daily X 28 days, orally, empty stomach, approximately same time each day Intervention: Drug: Placebo; Experimental: SAR302503 400 mg once daily X 28 days, orally, empty stomach, approximately same time each day Intervention: Drug: SAR302503; Experimental: SAR302503 500 mg once daily X 28 days, orally, empty stomach, approximately same time each day Intervention: Drug: SAR302503
Publications *	Pardanani A, Harrison C, Cortes JE, Cervantes F, Mesa RA, Milligan D, Masszi T, Mishchenko E, Jourdan E, Vannucchi AM, Drummond MW, Jurgutis M, Kuliczkowski K, Gheorghita E, Passamonti F, Neumann F, Patki A, Gao G, Tefferi A. Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis: A Randomized Clinical Trial. JAMA Oncol. 2015 Aug;1(5):643-51. doi: 10.1001/jamaoncol.2015.1590.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: July 28, 2014)	289
Original Estimated Enrollment ICMJE; (submitted: September 20, 2011)	225
Actual Study Completion Date	June 2014
Actual Primary Completion Date	June 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion criteria: Diagnosis of Primary Myelofibrosis (MF) or Post-Polycythemia Vera MF or Post-Essential Thrombocythemia MF, according to the 2008 World Health Organization and International Working Group of Myelofibrosis Research and Treatment (IWG-MRT) criteria.; MF classified as high-risk or intermediate-risk level 2, as defined by modified IWG-MRT criteria (IPSS) (according to Cervantes F. et. al.; at screening).; Enlarged spleen, palpable at least 5 cm below costal margin.; At least 18 years of age.; Eastern Cooperative Oncology Group performance status of 0, 1, or 2 at study entry.; The following laboratory values within 14 days prior to the initiation of IMP or placebo:; Absolute Neutrophil Count (ANC) ≥1.0 x 10exp9/L; Platelet count ≥50 x 10exp9/L; Serum creatinine ≤1.5 x Upper Limit of Normal (ULN); Serum amylase and lipase ≤1.5 x ULN Exclusion criteria: Splenectomy.; Any chemotherapy (eg, hydroxyurea), immunomodulatory drug therapy (eg, thalidomide, interferon-alpha), Anagrelide, immunosuppressive therapy, corticosteroids >10 mg/day prednisone or equivalent, or growth factor treatment (eg, erythropoietin), or hormones (eg, androgens, danazol) within 14 days prior to initiation of IMP or placebo; darbepoetin use within 28 days prior to initiation of IMP or placebo. Patients who have had exposure to hydroxyurea (eg, hydrea) in the past may be enrolled into the study as long as it has not been administered within 14 days prior to initiation of IMP or placebo.; Major surgery within 28 days or radiation within 6 months prior to initiation of IMP or placebo.; Prior treatment with a Janus Kinase 2 (JAK2) inhibitor.; Known active (acute or chronic) Hepatitis A, B, or C; and hepatitis B and C carriers; AST or ALT ≥2.5 x ULN; Total Bilirubin:; Exclude if ≥3.0 x ULN; Patients with total bilirubin between 1.5-3.0 x ULN must be excluded if the direct bilirubin fraction is ≥25% of the total; 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.
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Australia, Austria, Belgium, Brazil, Canada, France, Germany, Hungary, Ireland, Israel, Italy, Korea, Republic of, Lithuania, Mexico, Poland, Portugal, Romania, Russian Federation, Singapore, South Africa, Spain, Sweden, Taiwan, United Kingdom, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01437787
Other Study ID Numbers ICMJE	EFC12153; 2011-001897-25 ( EudraCT Number ); U1111-1121-7170 ( Other Identifier: UTN )
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Sanofi
Study Sponsor ICMJE	Sanofi
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Clinical Sciences & Operations Sanofi
PRS Account	Sanofi
Verification Date	December 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP