NCT05949684进行中（未招募）3 期
A Phase 3, Open-label, Randomized Study to Compare the Efficacy and Safety of Luspatercept (ACE-536) vs Epoetin Alfa for the Treatment of Anemia Due to Revised International Prognostic Scoring System (IPSS-R) Very Low, Low, or Intermediate-Risk Myelodysplastic Syndrome (MDS) in Erythropoiesis-Stimulating Agent (ESA)-Naive Participants Who Are Non-Transfusion Dependent (NTD): The "ELEMENT-MDS" Trial
Bristol-Myers Squibb236 个研究点 分布在 9 个国家目标入组 402 人开始时间: 2023年10月24日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 402
- 试验地点
- 236
- 主要终点
- Number of participants with lower-risk non-transfusion dependent myelodysplastic syndromes (NTD-MDS) who converted to Transfusion Dependence (TD) during any continuous 16-week interval within the 96-week treatment period
研究概览
简要总结
The purpose of the study is to compare the efficacy and safety of Luspatercept vs epoetin alfa in the treatment of anemia in adults due to IPSS-R very low, low, intermediate-risk MDS in ESA-naïve participants who are non-transfusion dependent (NTD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Participant has documented diagnosis of MDS according to World Health Organization (WHO) 2016 that meet IPSS-R classification of very low, low, or intermediate-risk disease, (intermediate-risk of ≤ 3.5 IPSS-R score) confirmed via bone marrow aspirate and:.
- •i) < 5% blasts in bone marrow and < 1% blasts in peripheral blood.
- •Participant is not transfusion dependent (NTD) based on IWG2018 criteria.
- •Participant is erythropoiesis-stimulating agent naive. Participants may be randomized at the investigator's discretion if the participant received no more than 2 prior doses of epoetin alfa, epoetin alfa biosimilar, or darbepoetin alfa, with the last dose at least 8 weeks prior to randomization.
- •Participant has a baseline endogenous serum erythropoietin (sEPO) level of ≤ 500 U/L.
- •Participant has symptoms of anemia:.
- •i) Participant records a severity score of "moderate" or greater on at least 1 PGI-S item of fatigue, weakness, shortness of breath, or dizziness performed during the screening period.
- •Participant has a baseline Hb concentration prior to randomization of ≤ 9.5 g/dL. The baseline Hb will be calculated using the mean of the two lowest available Hb measurements within 16 weeks prior to randomization and must include at least one central lab Hb reading done within the screening period (no more than 35 days before randomization). The two Hb measurements must have been performed at least seven days apart. Hb levels less than 21 days following RBC transfusion should not be used. Split samples for local assessments are not required.
排除标准
- •Participant with secondary MDS (that is, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases).
- •Participant with known history of diagnosis of AML.
- •Participant with history of cerebrovascular accident (including ischemic, embolic, and hemorrhagic cerebrovascular accident), transient ischemic attack, deep venous thrombosis (including proximal and distal), pulmonary or arterial embolism, arterial thrombosis, or other venous thrombosis within 6 months prior to randomization.
- •Participant with a history of pure red cell aplasia and/or antibody against erythropoietin.
- •Other protocol-defined Inclusion/Exclusion criteria apply.
研究组 & 干预措施
Luspatercept
Experimental
干预措施: Luspatercept (Biological)
Epoetin Alfa
Active Comparator
干预措施: Epoetin Alfa (Biological)
结局指标
主要结局
Number of participants with lower-risk non-transfusion dependent myelodysplastic syndromes (NTD-MDS) who converted to Transfusion Dependence (TD) during any continuous 16-week interval within the 96-week treatment period
时间窗: Up to Week 96
TD is defined as ≥ 3 red blood cells (RBC) units/16 weeks assessed by International Working Group (IWG) 2018.
Number of participants with an increase from baseline in mean Hb values of ≥ 1.5 grams/deciliter (g/dL) in any continuous 16-week interval within the 48 week Treatment Period in the absence of transfusion
时间窗: Up to Week 48
次要结局
- Number of transfusions(Up to 5 years)
- Number of transfusions visits/units(Up to 5 years)
- Number of participants with adverse events (AEs)(Up to Week 102)
- Pharmacokinetics (PK): Serum concentration(Up to Week 96)
- Time to AML progression(Up to 5 years)
- Number of participants with an increase from baseline in mean Hb values of ≥ 1.5 grams/deciliter (g/dL) in any continuous 16-week interval within the 48 week Treatment Period in the absence of transfusion(Up to Week 48)
- Number of participants with an increase from baseline in mean Hb values of ≥ 1.5 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion(Up to Week 96)
- Mean Hb change over fixed 24-week periods compared to the baseline Hb(Baseline, Week 24, Week 48, Week 72, Week 96)
- Number of participants with an increase from baseline in mean Hb values of ≥ 1.0 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion(Up to Week 96)
- Number of participants with an increase from baseline in mean Hb values of ≥ 1.5 g/dL in any continuous 16-week interval within the 96-week treatment period in the absence of transfusion(Up to Week 96)
- Number of participants with TD by week 48(Up to Week 48)
- Time from first Luspatercept dose to first RBC transfusion(Up to 5 years)
- Duration of median hematologic improvement in erythroid response(mHI-E) in participants with an increase from baseline in mean Hb values of ≥1.5g/dL in any continuous 16-week interval within 48-week treatment period in absence of transfusion(Up to Week 48)
- Number of participants with RBC transfusion independence over at least a consecutive 24-week period(Up to 5 years)
- Time to TD (IWG 2018 defined as ≥ 3 RBC units/16 weeks) during any continuous 16-week interval until the end of study(Up to 5 years)
- Duration of median hematologic improvement in erythroid response(mHI-E) in participants with an increase from baseline in mean Hb values of ≥1.5g/dL in any continuous 16-week interval within 96-week treatment period in absence of transfusion(Up to Week 96)
- Number of participants with antidrug antibody (ADA) (positive or negative)(Up to Week 102)
- Number of participants with a neutrophil response at Week 24, Week 48 and Week 96(Up to Week 96)
- Number of participants with acute myeloid leukemia (AML) progression(Up to 5 years)
- Number of participants with high risk myelodysplastic syndromes (MDS) progression(Up to 5 years)
- Time to high-risk MDS progression(Up to 5 years)
- Time from first dose to first day of response (increase in mean Hb values of ≥ 1.5 g/dL in any continuous 16-week interval within the 48-week Treatment Period in the absence of transfusion)(Up to Week 48)
- Time from first dose to first day of response (increase in mean Hb values of ≥ 1.5 g/dL in any continuous 16-week interval within the 96-week Treatment Period in the absence of transfusion)(Up to Week 96)
- Change from baseline in subscales of self-reported health-related quality-of-life (HRQoL) assessed by the Functional Assessment of Cancer Therapy - Anemia (FACT-An)(Baseline, Up to 5 years)
- Change from baseline in self-reported HRQoL assessed by the European quality of life questionnaire 5-dimension (EQ-5D-5L)(Baseline, Up to 5 years)
- PK: Area under the plasma concentration time curve (AUC)(Up to Week 96)
- Number of participants with a platelet response at Week 24, Week 48 and Week 96(Up to Week 96)
- Time from date of randomization up to death due to any cause(Up to 5 years)
- Mean Hb change over fixed 24-week periods compared to the baseline Hb(Week 24, Week 48, Week 72, Week 96)
- Duration of mHI-E in participants with an increase from baseline in mean Hb values of ≥1.5g/dL in any continuous 16-week interval within the 48-week and 96-week treatment period in absence of transfusion(Up to Week 96)
- Time from first dose to first day of response (increase in mean Hb values of ≥ 1.5 g/dL in any continuous 16-week interval within the 48-week and 96-week Treatment Period in the absence of transfusion)(Up to Week 96)
- Change from baseline in subscales of self-reported health-related quality-of-life (HRQoL) assessed by the Functional Assessment of Cancer Therapy - Anemia (FACT-An)(Up to 5 years)
- Change from baseline in self-reported HRQoL assessed by the European quality of life questionnaire 5-dimension (EQ-5D-5L)(Up to 5 years)
- Number of participants with adverse events (AEs)(Up to 42 days post last dose)
- Number of participants with antidrug antibody (ADA) (positive or negative)(Up to Week 96)
- Number of participants with an increase from baseline in mean Hb values of ≥ 1.5 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion(Up to Week 48)
- Number of participants with an increase from baseline in mean Hb values of ≥ 1.5 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion(From Week 49 to Week 96)
- Number of participants with an increase from baseline in mean Hb values of ≥ 1.0 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion(Up to Week 48)
- Number of participants with an increase from baseline in mean Hb values of ≥ 1.0 g/dL in any continuous 24-week interval within the 48-week and 96-week treatment period in the absence of transfusion(From Week 49 to Week 96)
研究者
研究点 (236)
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