Phase 2 Study of SAR302503 in Patients With Myelofibrosis

Phase 2

Completed

• Conditions: Hematopoietic Neoplasm
• Interventions: Drug: SAR302503

• Registration Number: NCT01420770
• 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 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.

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.

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.

Study Timeline

• Study Start: 2011-08
• Study First Submitted: 2011-08-11
• Study First Submitted QC: 2011-08-19
• Study First Posted: 2011-08-22
• Primary Completion: 2014-04
• Study Completion: 2014-04
• Status Verified: 2016-02
• Disposition First Submitted: 2016-02-17
• Disposition First Submitted QC: 2016-02-17
• Disposition First Posted: 2016-03-16
• Last Update Submitted: 2025-03-03
• Last Update Posted: 2025-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SAR302503 400 mg qd	SAR302503	daily X 28 days
SAR302503 500 mg qd	SAR302503	daily X 28 days
SAR02503 300 mg qd	SAR302503	daily X 28 days

Primary Outcome Measures

Name	Time	Method
The percent change in spleen volume based on MRI at the end of Cycle 3 relative to baseline	1 year

Secondary Outcome Measures

Name	Time	Method
The percent change in spleen volume based on MRI at Cycle 6 EOC compared to baseline	1 year
Duration of maintenance of ≥35% reduction in spleen volume relative to baseline, as measured at Cycle 3 EOC, at Cycle 6 EOC, after a year, after 18 months and after two years and at end of treatment (EOT).	1 year
Characterization of the safety profile of SAR302503, including the frequency, duration, and severity of adverse events (AEs) 2 years	1 year
In patients with the JAK2V617F mutation, change in peripheral blood granulocyte JAK2V617F allele burden from baseline to Cycle 3 EOC, to Cycle 6 EOC and at the end of every third cycle thereafter until Cycle 12 EOC and EOT	1 year
The proportion of patients who achieve ≥35% reduction in spleen volume from baseline, to Cycle 6 end of cycle (EOC)	1 year
Area under the plasma concentration versus time curve (AUC) of SAR302503	1 year
Peak plasma concentration (CMax) of SAR302503	1 year

Trial Locations

Locations (4)

Investigational Site Number 840001; 🇺🇸 San Francisco, California, United States

Investigational Site Number 840003; 🇺🇸 Ann Arbor, Michigan, United States

Investigational Site Number 840006; 🇺🇸 Rochester, Minnesota, United States

Investigational Site Number 840007; 🇺🇸 Canton, Ohio, United States