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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

Phase 2
Completed
Conditions
Myelofibrosis
Interventions
Registration Number
NCT01692366
Lead Sponsor
Bristol-Myers Squibb
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
8
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SAR302503 400 mgSAR302503SAR302503 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 300mgSAR302503SAR302503 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 500 mgSAR302503SAR302503 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
Primary Outcome Measures
NameTimeMethod
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:24 weeks
Secondary Outcome Measures
NameTimeMethod
Number of patients with Serious Adverse events using NCI CTCAE v4.03, clinical parameters and vital signsFrom baseline to the 30 days after last drug administration
Measurements of SAR302503 pharmacokinetic endpoints including Cmax, Tmax, and AUC0-24SAR302503, 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 MFSAF24 weeks
Duration of maintenance of ≥35% reduction in spleen volumeFrom baseline to the 30 days after last drug administration
Percent change from baseline in spleen volume measured by MRI24 weeks
Percent change from baseline in spleen size measured by palpation24 weeks
Proportion of patients with any grade reduction in reticulin fibrosis24 weeks

Trial Locations

Locations (7)

Investigational Site Number 392002

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Bunkyo-Ku, Japan

Investigational Site Number 392009

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Shinjuku-Ku, Japan

Investigational Site Number 392008

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Shinjuku-Ku, Japan

Investigational Site Number 392004

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Sendai-Shi, Japan

Investigational Site Number 392003

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Suita-Shi, Japan

Investigational Site Number 392010

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Akita-Shi, Japan

Investigational Site Number 392006

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Bunkyo-Ku, Japan

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