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Phase 2 Study of SAR302503 in Patients With Myelofibrosis

Primary Purpose

Hematopoietic Neoplasm

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
SAR302503
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematopoietic Neoplasm

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  • 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.

Exclusion criteria:

  • 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.
  • Unable to swallow capsules
  • Presence of any gastric or other disorder that would inhibit absorption of oral medication.

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

Sites / Locations

  • Investigational Site Number 840001
  • Investigational Site Number 840003
  • Investigational Site Number 840006
  • Investigational Site Number 840007

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

SAR02503 300 mg qd

SAR302503 400 mg qd

SAR302503 500 mg qd

Arm Description

daily X 28 days

daily X 28 days

daily X 28 days

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

The proportion of patients who achieve ≥35% reduction in spleen volume from baseline, to Cycle 6 end of cycle (EOC)
The percent change in spleen volume based on MRI at Cycle 6 EOC compared to baseline
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).
Characterization of the safety profile of SAR302503, including the frequency, duration, and severity of adverse events (AEs) 2 years
Area under the plasma concentration versus time curve (AUC) of SAR302503
Peak plasma concentration (CMax) of SAR302503
In patients with the JAK2V617F mutation, change in peripheral blood granulocyte JAK2V617F allele burden from baseline to Cycle 3 EOC, to Cycle 6 EOC and at the end of every third cycle thereafter until Cycle 12 EOC and EOT

Full Information

First Posted
August 11, 2011
Last Updated
February 17, 2016
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT01420770
Brief Title
Phase 2 Study of SAR302503 in Patients With Myelofibrosis
Official Title
A Phase 2 Randomized, Open-Label, Dose-Ranging Study of the Efficacy and Safety of Orally Administered SAR302503 in Patients With Intermediate-2 or High Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
The duration of the study for an individual patient will include a period to assess eligibility (screening period 28 days), followed by a treatment period of at least 1 cycle (28 days) of study treatment, and an end-of-treatment visit at least 30 days following the last administration of study drug. However, treatment may continue if patients are deriving benefit and do not have unacceptable toxicity or meet study withdrawal criteria. The study duration will be approximately 16 months which includes a 3-month enrollment period followed by a 12-month treatment period following the last patient enrolled followed by a 30-day follow-up period. The cut-off date for the analysis of the primary endpoint of response will be in maximum at the end of 3 months after the date of first dose of study drug of the last treated patient. The final analysis will be performed after the last enrolled patient completes the Cycle12 assessment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematopoietic Neoplasm

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SAR02503 300 mg qd
Arm Type
Experimental
Arm Description
daily X 28 days
Arm Title
SAR302503 400 mg qd
Arm Type
Experimental
Arm Description
daily X 28 days
Arm Title
SAR302503 500 mg qd
Arm Type
Experimental
Arm Description
daily X 28 days
Intervention Type
Drug
Intervention Name(s)
SAR302503
Intervention Description
Pharmaceutical form:capsule Route of administration: oral
Primary Outcome Measure Information:
Title
The percent change in spleen volume based on MRI at the end of Cycle 3 relative to baseline
Time Frame
1 year
Secondary Outcome Measure Information:
Title
The proportion of patients who achieve ≥35% reduction in spleen volume from baseline, to Cycle 6 end of cycle (EOC)
Time Frame
1 year
Title
The percent change in spleen volume based on MRI at Cycle 6 EOC compared to baseline
Time Frame
1 year
Title
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).
Time Frame
1 year
Title
Characterization of the safety profile of SAR302503, including the frequency, duration, and severity of adverse events (AEs) 2 years
Time Frame
1 year
Title
Area under the plasma concentration versus time curve (AUC) of SAR302503
Time Frame
1 year
Title
Peak plasma concentration (CMax) of SAR302503
Time Frame
1 year
Title
In patients with the JAK2V617F mutation, change in peripheral blood granulocyte JAK2V617F allele burden from baseline to Cycle 3 EOC, to Cycle 6 EOC and at the end of every third cycle thereafter until Cycle 12 EOC and EOT
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: 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. Exclusion criteria: 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. Unable to swallow capsules Presence of any gastric or other disorder that would inhibit absorption of oral medication. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 840001
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Facility Name
Investigational Site Number 840003
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0759
Country
United States
Facility Name
Investigational Site Number 840006
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Investigational Site Number 840007
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States

12. IPD Sharing Statement

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Phase 2 Study of SAR302503 in Patients With Myelofibrosis

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