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

• ClinicalTrials.gov Identifier: NCT01437787
• Recruitment Status: Completed
• First Posted: September 21, 2011
• Last Update Posted: January 8, 2016
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

Tracking Information

• First Submitted Date: September 16, 2011
• First Posted Date: September 21, 2011
• Last Update Posted Date: January 8, 2016
• Study Start Date: December 2011
• Actual Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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 (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 Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis
• Official Title: 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Hematopoietic Neoplasm

Intervention

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 28, 2014): 289
• Original Estimated Enrollment (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

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, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: 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

Administrative Information

• NCT Number: NCT01437787
• Other Study ID Numbers: 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: Sanofi
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Sciences & Operations; Sanofi

• PRS Account: Sanofi
• Verification Date: December 2015