search
Back to results

Phase 2 Study in Japanese Patients With Intermediate-2 or High Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly

Primary Purpose

Myelofibrosis

Status
Completed
Phase
Phase 2
Locations
Japan
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 Myelofibrosis

Eligibility Criteria

20 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
  • Myelofibrosis classified as high-risk or intermediate-risk level 2
  • Enlarged spleen, palpable at least 5 cm below costal margin
  • Active symptoms of myelofibrosis
  • At least 20 years of age
  • Eastern Collaborative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 at study entry
  • Absence of active malignancy other than myelofibrosis
  • Written informed consent to participate.

Exclusion criteria:

  • Splenectomy.
  • Any recent 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.
  • Major surgery therapy within 28 days or radiation including spleen radiation within 6 months prior to initiation of study drug.
  • Concomitant treatment with or use of pharmaceutical or herbal agents known to be moderate or severe inhibitors or inducers CYP3A4.
  • 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 JAK 2 Inhibitor.
  • Treatment with aspirin in doses >150 mg/day
  • Known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness.
  • Pregnant or lactating female. Once the lactating female stop and participate in the study, she cannot re-start feeding the baby.
  • Women of childbearing potential, unless using effective contraception while on study drug. Otherwise patients must be post-menopausal (at least 1 years from last menstruation without other medical reason), or surgically sterile.
  • 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])

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 392010
  • Investigational Site Number 392002
  • Investigational Site Number 392006
  • Investigational Site Number 392004
  • Investigational Site Number 392008
  • Investigational Site Number 392009
  • Investigational Site Number 392003

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

SAR302503 300mg

SAR302503 400 mg

SAR302503 500 mg

Arm Description

SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 300mg. SAR302503 will be taken on an empty stomach at approximately the same time each day

SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 400 mg. SAR302503 will be taken on an empty stomach at approximately the same time each day

SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 500 mg. SAR302503 will be taken on an empty stomach at approximately the same time each day

Outcomes

Primary Outcome Measures

Response Rate (RR), defined as the proportion of subjects who have a ≥35% reduction as measured by MRI (or CT scan in subjects with contraindications for MRI). - Time Frame:

Secondary Outcome Measures

Number of patients with Serious Adverse events using NCI CTCAE v4.03, clinical parameters and vital signs
Measurements of SAR302503 pharmacokinetic endpoints including Cmax, Tmax, and AUC0-24
Symptom Response Rate (SRR): Proportion of subjects with a ≥50% reduction in the total symptom score using the modified MFSAF
Duration of maintenance of ≥35% reduction in spleen volume
Percent change from baseline in spleen volume measured by MRI
Percent change from baseline in spleen size measured by palpation
Proportion of patients with any grade reduction in reticulin fibrosis

Full Information

First Posted
September 10, 2012
Last Updated
September 19, 2014
Sponsor
Sanofi
search

1. Study Identification

Unique Protocol Identification Number
NCT01692366
Brief Title
Phase 2 Study in Japanese Patients With Intermediate-2 or High Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly
Official Title
A Phase 2 Open-Label, Dose-Ranging Study of the Efficacy and Safety of Orally Administered SAR302503 in Japanese 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
September 2014
Overall Recruitment Status
Completed
Study Start Date
November 2012 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
March 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 and combined for the response rate defined with the ≥35% reduction of spleen volume as determined by magnetic resonance imaging (MRI or computed tomography scan [CT] in patients with contraindications for MRI). Secondary Objectives: To evaluate the safety of SAR302503 for both pooled (300, 400, and 500mg) and individual doses population. To evaluate the pharmacokinetics (PK) of SAR302503 after single and repeat-dose. To evaluate the effect on Myelofibrosis (MF)-associated symptoms (Key MF symptoms) as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF). To evaluate the durability of splenic response. To evaluate the effect of SAR302503 on bone marrow with regard to changes on reticulin fibrosis.
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.

6. Conditions and Keywords

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

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
SAR302503 300mg
Arm Type
Experimental
Arm Description
SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 300mg. SAR302503 will be taken on an empty stomach at approximately the same time each day
Arm Title
SAR302503 400 mg
Arm Type
Experimental
Arm Description
SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 400 mg. SAR302503 will be taken on an empty stomach at approximately the same time each day
Arm Title
SAR302503 500 mg
Arm Type
Experimental
Arm Description
SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 500 mg. SAR302503 will be taken on an empty stomach at approximately the same time each day
Intervention Type
Drug
Intervention Name(s)
SAR302503
Intervention Description
Pharmaceutical form:Capsule Route of administration: oral
Primary Outcome Measure Information:
Title
Response Rate (RR), defined as the proportion of subjects who have a ≥35% reduction as measured by MRI (or CT scan in subjects with contraindications for MRI). - Time Frame:
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Number of patients with Serious Adverse events using NCI CTCAE v4.03, clinical parameters and vital signs
Time Frame
From baseline to the 30 days after last drug administration
Title
Measurements of SAR302503 pharmacokinetic endpoints including Cmax, Tmax, and AUC0-24
Time Frame
SAR302503, pre-dose and post-dose plasma collections will be obtained on Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 2, and Cycle 3 Day 1
Title
Symptom Response Rate (SRR): Proportion of subjects with a ≥50% reduction in the total symptom score using the modified MFSAF
Time Frame
24 weeks
Title
Duration of maintenance of ≥35% reduction in spleen volume
Time Frame
From baseline to the 30 days after last drug administration
Title
Percent change from baseline in spleen volume measured by MRI
Time Frame
24 weeks
Title
Percent change from baseline in spleen size measured by palpation
Time Frame
24 weeks
Title
Proportion of patients with any grade reduction in reticulin fibrosis
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria : Diagnosis of primary or post-polycythemia vera or post-essential thrombocythemia myelofibrosis Myelofibrosis classified as high-risk or intermediate-risk level 2 Enlarged spleen, palpable at least 5 cm below costal margin Active symptoms of myelofibrosis At least 20 years of age Eastern Collaborative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 at study entry Absence of active malignancy other than myelofibrosis Written informed consent to participate. Exclusion criteria: Splenectomy. Any recent 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. Major surgery therapy within 28 days or radiation including spleen radiation within 6 months prior to initiation of study drug. Concomitant treatment with or use of pharmaceutical or herbal agents known to be moderate or severe inhibitors or inducers CYP3A4. 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 JAK 2 Inhibitor. Treatment with aspirin in doses >150 mg/day Known human immunodeficiency virus or acquired immunodeficiency syndrome-related illness. Pregnant or lactating female. Once the lactating female stop and participate in the study, she cannot re-start feeding the baby. Women of childbearing potential, unless using effective contraception while on study drug. Otherwise patients must be post-menopausal (at least 1 years from last menstruation without other medical reason), or surgically sterile. 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]) 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 392010
City
Akita-Shi
Country
Japan
Facility Name
Investigational Site Number 392002
City
Bunkyo-Ku
Country
Japan
Facility Name
Investigational Site Number 392006
City
Bunkyo-Ku
Country
Japan
Facility Name
Investigational Site Number 392004
City
Sendai-Shi
Country
Japan
Facility Name
Investigational Site Number 392008
City
Shinjuku-Ku
Country
Japan
Facility Name
Investigational Site Number 392009
City
Shinjuku-Ku
Country
Japan
Facility Name
Investigational Site Number 392003
City
Suita-Shi
Country
Japan

12. IPD Sharing Statement

Learn more about this trial

Phase 2 Study in Japanese Patients With Intermediate-2 or High Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly

We'll reach out to this number within 24 hrs