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:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01692366
First received: September 10, 2012
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

Primary Objective:

To evaluate the efficacy of daily oral doses of 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 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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • Symptom Response Rate (SRR): Proportion of subjects with a ≥50% reduction in the total symptom score using the modified MFSAF [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Duration of maintenance of ≥35% reduction in spleen volume [ Time Frame: From baseline to the 30 days after last drug administration ] [ Designated as safety issue: No ]
  • Percent change from baseline in spleen volume measured by MRI [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Percent change from baseline in spleen size measured by palpation [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Proportion of patients with any grade reduction in reticulin fibrosis [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

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 400mg
SAR302503 will be self-administered, orally, once daily, as a single agent, in consecutive, 28-day cycles at the dose level of 400mg. 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

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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 392009
Shinjuku-Ku, Japan
Investigational Site Number 392008
Shinjuku-Ku, Japan
Investigational Site Number 392003
Suita-Shi, Japan
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01692366     History of Changes
Other Study ID Numbers: ARD12888, U1111-1130-3710
Study First Received: September 10, 2012
Last Updated: April 7, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

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

ClinicalTrials.gov processed this record on July 24, 2014