Phase 2 Study of SAR302503 in Patients With Myelofibrosis

NCT01420770 | Completed Phase 2

• 2 other identifiers: ARD11936U1111-1119-2965
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 4

Brief Summary

Primary Objective: \- To evaluate the efficacy of daily oral doses of 300 mg, 400 mg, and 500 mg SAR302503 for the reduction of spleen volume as determined by magnetic resonance imaging (MRI). Secondary Objectives:

• To evaluate the safety of SAR302503.
• To evaluate the pharmacokinetics (PK) of SAR302503 after single and repeat doses.
• To evaluate the pharmacodynamics of SAR302503 as measured by changes in JAK2V617F allele burden in those patients with JAK2V617F mutation, changes in substrate phosphorylation in the JAK-STAT signal transduction pathway, and the expression of cytokines.
• To measure improvement in baseline Myeloproliferative Neoplasm (MPN) associated symptoms, as well as overall impact in quality of life (QOL), through serial administration of the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF).
• To measure generic health-related quality of life (HRQL) and utility values using the EQ-5D questionnaire.

Conditions

Hematopoietic Neoplasm

Outcome Measures

Primary Outcomes (1)

• The percent change in spleen volume based on MRI at the end of Cycle 3 relative to baseline

  1 year

Secondary Outcomes (7)

• The proportion of patients who achieve ≥35% reduction in spleen volume from baseline, to Cycle 6 end of cycle (EOC)

  1 year

• The percent change in spleen volume based on MRI at Cycle 6 EOC compared to baseline

  1 year

• Duration of maintenance of ≥35% reduction in spleen volume relative to baseline, as measured at Cycle 3 EOC, at Cycle 6 EOC, after a year, after 18 months and after two years and at end of treatment (EOT).

  1 year

• Characterization of the safety profile of SAR302503, including the frequency, duration, and severity of adverse events (AEs) 2 years

  1 year

• Area under the plasma concentration versus time curve (AUC) of SAR302503

  1 year

Study Arms (3)

SAR02503 300 mg qd

EXPERIMENTAL

daily X 28 days

Drug: SAR302503

SAR302503 400 mg qd

EXPERIMENTAL

daily X 28 days

Drug: SAR302503

SAR302503 500 mg qd

EXPERIMENTAL

daily X 28 days

Drug: SAR302503

Interventions

SAR302503 DRUG

Pharmaceutical form:capsule Route of administration: oral

SAR02503 300 mg qd; SAR302503 400 mg qd; SAR302503 500 mg qd

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of primary or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (Post-ET MF) according to the 2008 World Health Organization (WHO) criteria
• Myelofibrosis classified as high-risk or intermediate-risk level 2, as defined by International Working Group - Myelofibrosis Research and Treatment (IWG-MRT)
• Enlarged spleen, palpable at least 5 cm below costal margin
• At least 18 years of age.
• Eastern Collaborative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 at study entry.
• Adequate organ function
• Absence of active malignancy other than MF, except adequately treated basal cell carcinoma and squamous cell carcinoma of the skin, cervical carcinoma in situ or other malignancies that have been stable and off therapy for 5 years.
• Written informed consent to participate.
• Willing to comply with scheduled visits, treatment plans, laboratory assessments, and other study-related procedures.

You may not qualify if:

• Splenectomy.
• Any 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; darbepoetin use within 28 days prior to initiation of study drug.
• Major surgery therapy within 28 days or radiation within 6 months prior to initiation of study drug.
• Concomitant treatment with or use of pharmaceutical or herbal agents known to be at least moderate inhibitors or inducers Cytochrome P450 3A4 (CYP3A4), unless approved by the sponsor.
• 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 Janus kinase 2 (JAK 2) Inhibitor,
• Contraindications for undergoing Magnetic resonance imaging (MRI) (eg. metal implants).
• Pregnant or lactating female.
• Women of childbearing potential, unless using effective contraception while on study drug.
• Men who partner with a woman of childbearing potential, unless they agree to use effective contraception while on study drug.
• Known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness.
• Clinically active hepatitis B or C.
• Any severe acute or chronic medical, neurological, or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with interpretation of study results and, in the Investigator's opinion, would make the patient inappropriate for entry into this study.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (4)

Investigational Site Number 840001

San Francisco, California, 94143, United States

Location

Investigational Site Number 840003

Ann Arbor, Michigan, 48109-0759, United States

Location

Investigational Site Number 840006

Rochester, Minnesota, 55905, United States

Location

Investigational Site Number 840007

Canton, Ohio, 44718, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

fedratinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2011
• First Posted: August 22, 2011
• Study Start: August 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: March 5, 2025

Record last verified: 2016-02

Locations

US (4)