Study With SAR302503 in Patients With Polycythemia Vera or Essential Thrombocythemia

NCT01420783 | Completed Phase 2

• 3 other identifiers: ARD120422011-001847-58U1111-1121-4203
• Study Type: interventional
• Target: 81
• Locations: 9 countries
• Sites: 35

Brief Summary

Primary Objective:

• Dose Ranging Phase: To evaluate the efficacy of daily oral doses of 100, 200, and 400 mg SAR302503 in patients with PV and ET who are resistant or intolerant to hydroxyurea (per European LeukemiaNet criteria) for :
• Inducing absence of phlebotomy and a hematocrit below 45% for a minimum of 3 months in patients with polycythemia vera, and
• Reduction of platelet count to ≤400 x 10x9/L for a minimum of 3 months in patients with essential thrombocythemia.
• PV Dose Expansion Phase and ET Dose Ranging Phase (only 600 mg dose group): To evaluate the efficacy of daily oral SAR302503 in patients with PV and ET who are resistant or intolerant to hydroxyurea (per European LeukemiaNet criteria) for:
• Inducing absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit in patients with PV, and
• Reduction of platelet count to ≤400 x 10x9/L beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit in patients with ET. Secondary Objectives:
• To evaluate the safety of SAR302503.
• To evaluate the efficacy of SAR302503 in patients with PV who are resistant or intolerant to hydroxyurea for inducing absence of phlebotomy eligibility.
• To evaluate the efficacy of SAR302503 in patients with ET who are resistant or intolerant to hydroxyurea for reduction of platelet counts.
• To evaluate the efficacy of SAR302503 in inducing complete and partial responses beginning at Day 1 of Cycle 6 visit through Cycle 8.
• To evaluate splenic response as measured by spleen volume using MRI or CT.
• To evaluate the pharmacokinetics of SAR302503 after single and repeat doses.
• To evaluate the pharmacodynamics of SAR302503 as measured by changes in JAK2V617F allele burden in patients with JAK2V617F mutation, and STAT3 phosphorylation inhibition.
• To measure improvement in baseline myeloproliferative neoplasm (MPN)-associated symptoms, as well as overall impact on quality of life.
• To measure generic health-related quality of life and utility value using the EuroQol Group (EQ-5DTM) questionnaire.

Conditions

Hematopoietic Neoplasm

Outcome Measures

Primary Outcomes (3)

• Dose Ranging Phase: Proportion of PV patients with absence of phlebotomy and hematocrit below 45% and proportion of ET patients with a platelet count ≤ 400 x 10x9/L for a minimum of 3 months during the first 8 cycles of therapy.

  2 years

• PV Dose Expansion Phase: Proportion of PV patients with absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit.

  2 years

• ET Dose Ranging Phase (only 600 mg dose group): Proportion of ET patients with a platelet count ≤400 x 10x9/L beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit.

  2 years

Secondary Outcomes (11)

• Proportion of PV patients with absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit through Cycle 8 (for PV dose expansion phase only).

  2 years

• Proportion of ET patients with platelet count ≤400 x 10x9/L beginning at Day 1 of Cycle 4 visit and continuing through Cycle 8.

  2 years

• Characterization of clinicohematologic response (CR, PR, and no Response) defined by European LeukemiaNet beginning at Day 1 of Cycle 6 visit through Cycle 8.

  2 years

• Percent change in spleen volume (per Magnetic Resonance Imaging (MRI)) at the end of Cycles 4 and 8 or end of treatment (EOT) relative to baseline.

  2 years

• Proportion of patients with a ≥ 35% reduction in spleen volume (per Magnetic Resonance Imaging (MRI)) at the end of Cycles 4 and 8 or end of treatment (EOT) relative to baseline.

  2 years

Study Arms (4)

SAR302503 100 mg

EXPERIMENTAL

once daily X 28 days

Drug: SAR302503

SAR302503 200 mg

EXPERIMENTAL

once daily X 28 days

Drug: SAR302503

SAR302503 400 mg

EXPERIMENTAL

once daily X 28 days

Drug: SAR302503

SAR302503 600 mg

EXPERIMENTAL

once daily X 28 days

Drug: SAR302503

Interventions

SAR302503 DRUG

Pharmaceutical form:capsule Route of administration: oral

SAR302503 100 mg; SAR302503 200 mg; SAR302503 400 mg; SAR302503 600 mg

Eligibility Criteria

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

You may qualify if:

• Has had a diagnosis of hydroxyurea resistant or intolerant polycythemia vera (PV) or essential thrombocythemia (ET) documented at Screening.
• Polycythemia vera or essential thrombocythemia defined according to the revised WHO criteria.
• Polycythemia vera resistance or intolerance to hydroxyurea is defined as polycythemia vera patients on hydroxyurea with a hematocrit \>45%, or phlebotomy twice in the last 6 months and at least once in the last 3 months.
• Essential thrombocythemia resistance or intolerance to hydroxurea is defined as essential thrombocythemia patients on HU with platelet count \>600 x 10x9/L.
• Dose Expansion Phase (polycythemia vera) and 600 mg/day group (essential thrombocythemia):
• Has had a diagnosis of polycythemia vera or essential thrombocythemia according to the revised WHO 2008 criteria.
• PV patients must be resistant or intolerant to hydroxyurea.
• ET patients must be resistant or intolerant to hydroxyurea.
• Provide written informed consent to participate.

You may not qualify if:

• Less than 18 years of age.
• Participation in any study of an investigational agent (drug, biologic, device) within 30 days prior to initiation of study drug, unless during non-treatment phase. (Prior treatment with another JAK2 inhibitor is allowed.)
• Unwilling to comply with scheduled visits, treatment plans, laboratory assessments, and other study-related procedures.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 3 or 4 at study entry.
• Splenectomy.
• Active malignancy other than polycythemia vera or essential thrombocythemia, 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.
• Major surgery within 28 days or radiation within 3 months prior to initiation of study drug.
• Active acute infection requiring antibiotics.
• Known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness.
• Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass surgery, transient ischemic attack, or pulmonary embolism within 3 months prior to initiation of study drug.
• 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.
• Inadequate organ function.
• 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 \[NASH\]).
• Concomitant treatment with or use of drugs or herbal agents known to be at least moderate inhibitors or inducers cytochrome P450 3A4 (CYP3A4).

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (35)

Investigational Site Number 840008

Scottsdale, Arizona, 85259-5499, United States

Location

Investigational Site Number 840004

La Jolla, California, 92093, United States

Location

Investigational Site Number 840005

Los Angeles, California, 90033, United States

Location

Investigational Site Number 840011

Palo Alto, California, 94301, United States

Location

Investigational Site Number 840010

Ann Arbor, Michigan, 48109-0759, United States

Location

Investigational Site Number 840007

Rochester, Minnesota, 55905, United States

Location

Investigational Site Number 840003

St Louis, Missouri, 63110, United States

Location

Investigational Site Number 840001

Houston, Texas, 77030, United States

Location

Investigational Site Number 036001

Clayton, 3168, Australia

Location

Investigational Site Number 036002

Kingswood, 2747, Australia

Location

Investigational Site Number 036004

Kogarah, 2217, Australia

Location

Investigational Site Number 036003

Randwick, 2031, Australia

Location

Investigational Site Number 124002

Montreal, H3T 1E2, Canada

Location

Investigational Site Number 124003

Toronto, M5G 2M9, Canada

Location

Investigational Site Number 124001

Vancouver, V6Z 1Y6, Canada

Location

Investigational Site Number 250004

Brest, 29609, France

Location

Investigational Site Number 250003

Marseille, 13273, France

Location

Investigational Site Number 250001

Paris, 75475, France

Location

Investigational Site Number 276004

Frankfurt am Main, 60590, Germany

Location

Investigational Site Number 276003

Mannheim, 68167, Germany

Location

Investigational Site Number 380003

Bologna, 40138, Italy

Location

Investigational Site Number 380001

Florence, 50134, Italy

Location

Investigational Site Number 380004

Orbassano, 10043, Italy

Location

Investigational Site Number 410001

Seongnam, 463-707, South Korea

Location

Investigational Site Number 410003

Seoul, 110-744, South Korea

Location

Investigational Site Number 410004

Seoul, 120-752, South Korea

Location

Investigational Site Number 410002

Seoul, 135-710, South Korea

Location

Investigational Site Number 724004

Badalona, 08916, Spain

Location

Investigational Site Number 724001

Barcelona, 08036, Spain

Location

Investigational Site Number 724003

Madrid, 28046, Spain

Location

Investigational Site Number 724002

Valencia, Spain

Location

Investigational Site Number 826001

Belfast, BT9 7AB, United Kingdom

Location

Investigational Site Number 826006

Birmingham, B9 5SS, United Kingdom

Location

Investigational Site Number 826003

London, SE1 7EH, United Kingdom

Location

Investigational Site Number 826004

London, W12 0HS, United Kingdom

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: October 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: May 1, 2014
• Last Updated: March 5, 2025

Record last verified: 2016-02

Locations

GB (4); FR (3); KR (4); DE (2); IT (3); ES (4); CA (3); AU (4); US (8)