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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 289
- 试验地点
- 101
- 主要终点
- Response Rate (RR): Percentage of Participants Who Had a >=35% Reduction From Baseline in Volume of Spleen Size at The End Cycle 6
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Primary Myelofibrosis (MF) or Post-Polycythemia Vera MF or Post-Essential Thrombocythemia MF, according to the 2008 World Health Organization and International Working Group of Myelofibrosis Research and Treatment (IWG-MRT) criteria.
- •MF classified as high-risk or intermediate-risk level 2, as defined by modified IWG-MRT criteria (IPSS) (according to Cervantes F. et. al.; at screening).
- •Enlarged spleen, palpable at least 5 cm below costal margin.
- •At least 18 years of age.
- •Eastern Cooperative Oncology Group performance status of 0, 1, or 2 at study entry.
- •The following laboratory values within 14 days prior to the initiation of IMP or placebo:
- •Absolute Neutrophil Count (ANC) ≥1.0 x 10exp9/L
- •Platelet count ≥50 x 10exp9/L
- •Serum creatinine ≤1.5 x Upper Limit of Normal (ULN)
- •Serum amylase and lipase ≤1.5 x ULN
排除标准
- •Splenectomy.
- •Any chemotherapy (eg, hydroxyurea), immunomodulatory drug therapy (eg, thalidomide, interferon-alpha), Anagrelide, immunosuppressive therapy, corticosteroids >10 mg/day prednisone or equivalent, or growth factor treatment (eg, erythropoietin), or hormones (eg, androgens, danazol) within 14 days prior to initiation of IMP or placebo; darbepoetin use within 28 days prior to initiation of IMP or placebo. Patients who have had exposure to hydroxyurea (eg, hydrea) in the past may be enrolled into the study as long as it has not been administered within 14 days prior to initiation of IMP or placebo.
- •Major surgery within 28 days or radiation within 6 months prior to initiation of IMP or placebo.
- •Prior treatment with a Janus Kinase 2 (JAK2) inhibitor.
- •Known active (acute or chronic) Hepatitis A, B, or C; and hepatitis B and C carriers
- •AST or ALT ≥2.5 x ULN
- •Total Bilirubin:
- •Exclude if ≥3.0 x ULN
- •Patients with total bilirubin between 1.5-3.0 x ULN must be excluded if the direct bilirubin fraction is ≥25% of the total
- •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.
研究组 & 干预措施
SAR302503 500 mg
once daily X 28 days, orally, empty stomach, approximately same time each day
干预措施: SAR302503 (Drug)
SAR302503 400 mg
once daily X 28 days, orally, empty stomach, approximately same time each day
干预措施: SAR302503 (Drug)
Placebo comparator
once daily X 28 days, orally, empty stomach, approximately same time each day
干预措施: Placebo (Drug)
结局指标
主要结局
Response Rate (RR): Percentage of Participants Who Had a >=35% Reduction From Baseline in Volume of Spleen Size at The End Cycle 6
时间窗: Baseline, Week 24
Spleen volume was determined by magnetic resonance imaging (MRI) (or computed tomography scan in participants with contraindications for MRI) at baseline and at the end of cycle 6 with a confirmatory scan approximately 4 weeks after the end of Cycle 6. The MRI or CT imaging results reviewed in a blinded manner by an Independent Review Committee (IRC). Analysis was performed on intent-to-treat (ITT) population defined as all randomized participants who signed informed consent form (ICF).
次要结局
- Symptom Response Rate (SRR): Percentage of Participants With >=50% Reduction From Baseline in the Total Symptom Score at End of Cycle 6(Baseline, Week 24)
- Percentage of Participants Who Had >=25% Reduction From Baseline in Volume of Spleen Size at End of Cycle 6(Baseline, Week 24)