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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01692366
First Posted: September 25, 2012
Last Update Posted: September 22, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Sanofi
  Purpose

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.

Condition Intervention Phase
Myelofibrosis Drug: SAR302503 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Sanofi:

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: [ Time Frame: 24 weeks ]

Secondary Outcome Measures:
  • 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 ]
  • 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 ]
  • Symptom Response Rate (SRR): Proportion of subjects with a ≥50% reduction in the total symptom score using the modified MFSAF [ Time Frame: 24 weeks ]
  • Duration of maintenance of ≥35% reduction in spleen volume [ Time Frame: From baseline to the 30 days after last drug administration ]
  • Percent change from baseline in spleen volume measured by MRI [ Time Frame: 24 weeks ]
  • Percent change from baseline in spleen size measured by palpation [ Time Frame: 24 weeks ]
  • Proportion of patients with any grade reduction in reticulin fibrosis [ Time Frame: 24 weeks ]

Enrollment: 8
Study Start Date: November 2012
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SAR302503 300mg
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
Drug: SAR302503

Pharmaceutical form:Capsule

Route of administration: oral

Experimental: SAR302503 400 mg
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
Drug: SAR302503

Pharmaceutical form:Capsule

Route of administration: oral

Experimental: SAR302503 500 mg
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
Drug: SAR302503

Pharmaceutical form:Capsule

Route of administration: oral


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.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01692366


Locations
Japan
Investigational Site Number 392010
Akita-Shi, Japan
Investigational Site Number 392002
Bunkyo-Ku, Japan
Investigational Site Number 392006
Bunkyo-Ku, Japan
Investigational Site Number 392004
Sendai-Shi, Japan
Investigational Site Number 392008
Shinjuku-Ku, Japan
Investigational Site Number 392009
Shinjuku-Ku, Japan
Investigational Site Number 392003
Suita-Shi, Japan
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01692366     History of Changes
Other Study ID Numbers: ARD12888
U1111-1130-3710 ( Other Identifier: UTN )
First Submitted: September 10, 2012
First Posted: September 25, 2012
Last Update Posted: September 22, 2014
Last Verified: September 2014

Additional relevant MeSH terms:
Splenomegaly
Primary Myelofibrosis
Polycythemia
Polycythemia Vera
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders
Hypertrophy
Pathological Conditions, Anatomical