Phase 2 Study of SAR302503 in Patients With Myelofibrosis
| Status: | Completed |
|---|---|
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | August 2011 |
| End Date: | April 2014 |
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
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.
- 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.
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.
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.
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.
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