Neoplasms

Blood and Lymph Conditions

All Conditions

Heart and Blood Diseases

Rare Diseases

Polycythemia Vera

Polycythemia

Thrombocytosis

Thrombocythemia, Essential

Hematologic Neoplasms

Hematologic Diseases

Bone Marrow Neoplasms

Bone Marrow Diseases

Myeloproliferative Disorders

Blood Platelet Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Hemorrhagic Disorders

Essential Thrombocythemia

Chronic Myeloproliferative Disorders

Antineoplastic Agents

Antisickling Agents

All Drugs and Chemicals

Hydroxyurea

Pharmaceutical form:capsule

Route of administration: oral

SAR302503

Clinical Sciences & Operations

Primary Objective:

* Dose Ranging Phase: To evaluate the efficacy of daily oral doses of 100, 200, and 400 mg SAR302503 in patients with PV and ET who are resistant or intolerant to hydroxyurea (per European LeukemiaNet criteria) for :

  * Inducing absence of phlebotomy and a hematocrit below 45% for a minimum of 3 months in patients with polycythemia vera, and
  * Reduction of platelet count to ≤400 x 10x9/L for a minimum of 3 months in patients with essential thrombocythemia.
* PV Dose Expansion Phase and ET Dose Ranging Phase (only 600 mg dose group): To evaluate the efficacy of daily oral SAR302503 in patients with PV and ET who are resistant or intolerant to hydroxyurea (per European LeukemiaNet criteria) for:

  * Inducing absence of phlebotomy eligibility beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit in patients with PV, and
  * Reduction of platelet count to ≤400 x 10x9/L beginning at Day 1 of Cycle 4 visit and continuing through Day 1 of Cycle 6 visit in patients with ET.

Secondary Objectives:

* To evaluate the safety of SAR302503.
* To evaluate the efficacy of SAR302503 in patients with PV who are resistant or intolerant to hydroxyurea for inducing absence of phlebotomy eligibility.
* To evaluate the efficacy of SAR302503 in patients with ET who are resistant or intolerant to hydroxyurea for reduction of platelet counts.
* To evaluate the efficacy of SAR302503 in inducing complete and partial responses beginning at Day 1 of Cycle 6 visit through Cycle 8.
* To evaluate splenic response as measured by spleen volume using MRI or CT.
* To evaluate the pharmacokinetics of SAR302503 after single and repeat doses.
* To evaluate the pharmacodynamics of SAR302503 as measured by changes in JAK2V617F allele burden in patients with JAK2V617F mutation, and STAT3 phosphorylation inhibition.
* To measure improvement in baseline myeloproliferative neoplasm (MPN)-associated symptoms, as well as overall impact on quality of life.
* To measure generic health-related quality of life and utility value using the EuroQol Group (EQ-5DTM) questionnaire.

The duration of the study for an individual patient is at least 40 weeks and will include a period to assess eligibility (screening period) of up to 4 weeks (28 days), a treatment period of up to 8, 28-day cycles (32 weeks), and a follow-up visit 30 days following the last administration of study drug. Treatment may continue if the patient is deriving benefit and does not experience disease progression, unacceptable toxicity, or meet other study withdrawal criteria.

Per Protocol Amendment No. 5, accrual of patients with essential thrombocythemia is closed.

Study With SAR302503 in Patients With Polycythemia Vera or Essential Thrombocythemia

A Randomized Phase II, Open-Label Study of the Efficacy and Safety of Orally Administered SAR302503 in Patients With Polycythemia Vera (PV) or Essential Thrombocythemia (ET) Who Are Resistant or Intolerant to Hydroxyurea

Sanofi

Primary Myelofibrosis

once daily in consecutive 28-day cycles, flexible dosing regimen (the starting dose is 400mg/day), orally, empty stomach, approximately same time each day

Primary Objective:

- To evaluate the efficacy of once daily dose of SAR302503 in subjects previously treated with ruxolitinib and with a current diagnosis of intermediate-1 with symptoms, Intermediate-2 or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (Post-PV MF), or post-essential thrombocythemia myelofibrosis (Post-ET MF) based on the reduction of spleen volume at the end of 6 treatment cycles;

Secondary Objectives:

* To evaluate the effect of SAR302503 on Myelofibrosis (MF) associated symptoms as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) diary
* To evaluate the durability of splenic response
* To evaluate the splenic response to SAR302503 by palpation at the end of Cycle 6
* To evaluate the splenic response to SAR302503 at the end of Cycle 3
* To evaluate the effect of SAR302503 on the Janus kinase 2 (JAK2) V617F allele burden
* To evaluate the safety and tolerability of SAR302503 in this population
* To evaluate plasma concentrations of SAR302503 for population PK analysis, if warranted

The expected duration of the treatment in this study is approximately 8 months, based on a maximum 28-day screening period, followed by a 6-month (6-cycle) treatment period, and an EOT visit for subjects who will not continue the treatment after completing the 6 cycles of SAR302503, or discontinue the treatment early for any reasons as well as a follow-up visit which should occur 30 days after the last administration of SAR302503. Patients who continue to benefit clinically will be allowed to remain on study medication beyond the 6-month treatment period until the occurrence of disease progression or unacceptable toxicity.

Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib

A Phase II, Multicenter, Open Label, Single Arm Study of SAR302503 in Subjects Previously Treated With Ruxolitinib and With a Current Diagnosis of Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

Symptoms and General Pathology

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.

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.

Phase 2 Study of SAR302503 in Patients With Myelofibrosis

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

once daily X 28 days, orally, empty stomach, approximately same time each day

Placebo

Primary Objective:

* To evaluate the efficacy of daily oral doses of 400 mg or 500 mg of SAR302503 (Investigational Medicinal Product, IMP) compared to placebo in the reduction of spleen volume as determined by magnetic resonance imaging (MRI) (or computed tomography scan in patients with contraindications for MRI).

Secondary Objectives:

* To evaluate the effect on Myelofibrosis (MF)-associated symptoms (key MF symptoms) as measured by the modified Myelofibrosis Symptom Assessment Form (MFSAF) diary.
* To evaluate the Overall Survival of patients treated with either 400 mg/day or 500 mg/day of IMP as compared to placebo.
* To evaluate the Progression Free Survival of patients treated with either 400 mg/day or 500 mg/day of IMP as compared to placebo.
* To evaluate the durability of splenic response.
* To evaluate the safety of IMP.

The expected duration of a patient's treatment in this study is approximately 8 months, based on a maximum 28-day screening period, followed by a ≥6-month (6-cycle) treatment period, and an End Of Treatment (EOT) visit, which should be performed at least 30 days following the last administration of IMP or placebo.

Patients who continue to benefit clinically will be allowed to remain on IMP or placebo beyond the 6-month treatment period until the occurrence of disease progression or unacceptable toxicity.

Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis

A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Study of SAR302503 in Patients With Intermediate-2 or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly

This assessment will be conducted through the modified MFSAF diary, which will be completed during the week prior to Day 1 of each treatment cycle up to Cycle 6, and during the week prior to the end of Cycle 6.

Pharmaceutical Solutions

Adjuvants, Anesthesia

Central Nervous System Depressants

Psychotropic Drugs

Gastrointestinal Agents

Anti-Arrhythmia Agents

Antihypertensive Agents

Midazolam

Omeprazole

Metoprolol

Anesthetics

Hypnotics and Sedatives

Anti-Anxiety Agents

Anesthetics, Intravenous

Anesthetics, General

GABA Modulators

Neurotransmitter Agents

Sympatholytics

Adrenergic Agents

Adrenergic beta-1 Receptor Antagonists

Adrenergic beta-Antagonists

Adrenergic Antagonists

two single doses of omeprazol/metoprolol/midazolam on day-1 and day 15 without food, SAR302503 500 mg once daily without food for 15 days

SAR302503 500 mg once daily without food in 28-day per cycle

omeprazol

Pharmaceutical form:tablet

Route of administration: oral

metoprolol

Pharmaceutical form:solution

Route of administration: oral

midazolam

Primary Objective:

* To assess the effect of 15-day repeated oral doses of 500 mg SAR302503 on the cytochrome P450 activity using a CYP probe cocktail (2C19, 2D6 and 3A4).
* To document pharmacokinetics of SAR302503 after repeated 500 mg oral daily doses.

Secondary Objectives:

* To assess the safety profile of 15-day repeated oral doses of 500 mg SAR302503 in Segment 1
* To characterize the safety and tolerability of 28-day consecutive doses of 500 mg SAR302503 in Segment 2
* To determine antitumor activity in Segment 2

The duration of the study for an individual patient will include a period to assess eligibility (screening period 21 days), followed by a treatment period of at least 15 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 receiving benefit and do not have unacceptable toxicity or meet study withdrawal criteria.

Drug Interaction Study of SAR302503 in Patients With Solid Tumor

An Open-label, Two-treatment Crossover Pharmacokinetic Interaction Study of Repeated Doses of SAR302503 on Pharmacokinetics of a Single Dose Cocktail of Omeprazole, Metoprolol, and Midazolam Used as Probe Substrates for CYP2C19, CYP2D6 and CYP3A4 Activities, Respectively in Adult Patients With Refractory Solid Tumors

Hypertrophy

Pathological Conditions, Anatomical

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

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

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

Pharmaceutical form:Capsule

Route of administration: oral

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.

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.

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

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study With SAR302503 in Patients With Polycythemia Vera or Essential Thrombocythemia	NCT01420783	Hematopoietic N...	SAR302503	18 Years -	Sanofi
Phase II, Open Label, Single Arm Study of SAR302503 In Myelofibrosis Patients Previously Treated With Ruxolitinib	NCT01523171	Hematopoietic N...	SAR302503	18 Years -	Sanofi
Phase 2 Study of SAR302503 in Patients With Myelofibrosis	NCT01420770	Hematopoietic N...	SAR302503	18 Years -	Sanofi
Phase III Study of SAR302503 in Intermediate-2 and High Risk Patients With Myelofibrosis	NCT01437787	Hematopoietic N...	SAR302503 Placebo	18 Years -	Sanofi
Phase 2 Study of SAR302503 in Patients With Myelofibrosis	NCT01420770	Hematopoietic N...	SAR302503	18 Years -	Sanofi
Drug Interaction Study of SAR302503 in Patients With Solid Tumor	NCT01585623	Solid Tumor	SAR302503 omeprazol metoprolol midazolam	18 Years -	Sanofi
Phase 2 Study in Japanese Patients With Intermediate-2 or High Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly	NCT01692366	Myelofibrosis	SAR302503	20 Years -	Sanofi
Phase 2 Study in Japanese Patients With Intermediate-2 or High Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis With Splenomegaly	NCT01692366	Myelofibrosis	SAR302503	20 Years -	Sanofi

Spots Global Cancer Trial Database for sar302503

Every month we try and update this database with for sar302503 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for sar302503

Every month we try and update this database with for sar302503 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for sar302503 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.