2025-523544-12-00招募中3 期
A Phase 3, Multicenter, Open-Label, Randomized Trial to Compare the Efficacy and Safety of Elritercept versus Epoetin Alfa for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes in ESA-naïve Adult Participants Who Require Red Blood Cell Transfusions
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 114
- 试验地点
- 57
- 主要终点
- Proportion of participants who are RBC-TI for any consecutive ≥12-week period from Cycle 1 Day 1 (C1D1) through Week 24 with concurrent mean Hgb increase ≥1.5 g/dL from baseline
研究概览
简要总结
To evaluate the efficacy of elritercept on red blood cell transfusion independence (RBC-TI) for a minimum 12-week period within 24 weeks with concurrent mean hemoglobin (Hgb) increase ≥1.5 g/dL compared to epoetin alfa
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Male or female participants aged ≥18 years or older at time of signing the informed consent form (ICF).
- •Able to understand the purpose and risks of the trial and voluntarily sign an ICF prior to any trial-related procedures being conducted and authorization to use protected health information and personal data in accordance to national and local privacy regulations.
- •Documented diagnosis of myelodysplastic syndrome(s) (MDS) according to WHO 2016 classification that meets International Prognostic Scoring System – Revised (IPSS-R) classification of very low-, low-, or intermediate-risk disease, confirmed by central laboratory independent reviewer prior to randomization. Hemoglobin (Hgb), platelet, and absolute neutrophil count (ANC) values should be collected >14 days after red blood cell (RBC) transfusion or >7 days after platelet transfusion, unless otherwise considered to be pretransfusion values.
- •Bone marrow <5% blasts in an evaluable bone marrow collected at screening and confirmed by central pathology independent reviewer.
- •Endogenous serum erythropoietin s (EPO) level of <500 U/L. Should be results from blood samples collected >14 days following an RBC transfusion to evaluate for eligibility unless considered pretransfusion values.
- •Participant requires RBC transfusion, as documented by the following criteria (Section 8.1.1.3). A transfusion requirement of 2 to 6 packed red blood cells (pRBCs) units/8 weeks confirmed for a minimum of 8 weeks immediately preceding randomization. • Hgb levels at the time of or within 3 days prior to administration of a RBC transfusion must have been ≤9.0 g/dL (5.6 mmol/L) with symptoms of anemia (or ≤7 g/dL [4.3 mmol/L] in the absence of symptoms) in order for the transfusion to be counted towards meeting eligibility criteria. • RBC transfusions administered when Hgb levels were >9.0 g/dL (or >7 g/dL in the absence of symptoms) and/or RBC transfusions administered for elective surgery, infections or bleeding events will not qualify as a required transfusion for the purpose of meeting eligibility criteria or stratification.
- •Hgb <11.0 g/dL (6.8 mmol/L) after last RBC transfusion preceding randomization. Local laboratory is acceptable to facilitate randomization.
- •Eastern Cooperative Oncology Group score of 0, 1, or 2.
排除标准
- •Prior therapy with any of the following: a) Epoetin alfa • At the investigator’s discretion in consultation with the medical monitor, may be allowed if received no more than 2 doses of only epoetin alfa ≥8 weeks prior to randomization. No other erythropoiesis-stimulating agent (ESA) agent is allowed. b) Darbepoetin. c) Granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor administered ≤8 weeks (56 days) prior to randomization unless given for treatment of febrile neutropenia. d) Immunomodulatory drug (IMiDs) including lenalidomide. • At the investigator’s discretion in consultation with the medical monitor may be allowed if received ≤1 week of an IMiD ≥8 weeks prior to randomization. e) Hypomethylating agent. • At the investigator’s discretion, in consultation with the medical monitor may be allowed if received no more than 2 doses ≥8 weeks prior to randomization. f) Luspatercept, sotatercept, imetelstat, or elritercept. g) Immunosuppressive therapy. h) Hematopoeitic cell transplant. i) Iron chelation if administered ≤8 weeks prior to randomization. Participants on stable doses of iron chelation therapy for ≥8 weeks are allowed Vitamin B12 or folate therapy initiated within 4 weeks prior to randomization. Participants on stable replacement doses for ≥4 weeks and without ongoing concurrent vitamin B12 or folate deficiency are allowed. j) Androgen use within 8 weeks before randomization. Participants on stable androgen dosing for hypogonadism for ≥8 weeks are allowed. k) High-dose corticosteroid use within 4 weeks before randomization. Participants on stable chronic steroid doses of prednisone ≤10 mg/day or corticosteroid equivalent for ≥4 weeks are allowed. Other disease modifying treatments for autoimmune diseases may be allowed upon medical monitor review. l) Investigational agent or any other agent intended for treatment MDS treatment.
- •History of solid organ or bone marrow transplantation.
- •Active infection requiring intravenous antibiotics within 28 days or oral antibiotics within 14 days before randomization.
- •Known positive for HIV, active infectious hepatitis B virus (HBV), or active infectious hepatitis C virus (HCV). Participants without known positive history of HIV, HBV, and/or HCV do not require further testing, unless testing is mandated per local guidelines.
- •Body mass index ≥40 kg/m
- •Major surgery within 28 days before randomization.
- •New-onset seizures or poorly controlled seizures within 12 weeks prior to randomization are excluded from trial participation.
- •History of allergy/anaphylaxis to investigational product (including epoetin alfa) excipients (refer to the current elritercept investigator’s brochure for a list of excipients) or recombination proteins.
- •History of pure red cell aplasia and/or antibody against erythropoietin (EPO).
- •Any of the following laboratory abnormalities: a) ANC <500/μL (0.5×109/L). b) Platelet count <50,000/μL (50×109/L) or ≥450,000/μL (450×109/L). c) Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥3× upper limit of the normal (ULN). d) Total bilirubin ≥2×ULN. Participants with known history of Gilbert syndrome with unconjugated bilirubin <3×ULN are allowed. Higher levels if attributed to active RBC precursor destruction within the bone marrow (ineffective erythropoiesis) may be allowed upon medical monitor review. e) Estimated glomerular filtration rate <30 mL/min/1.73 m2 as determined by the Chronic Kidney Disease Epidemiology (CKD-EPI) collaboration equation (Delgado et al. 2021; Kramer et al. 2022). f) Ferritin ≤50 μg/L. g) Folate ≤2.0 ng/mL. h) Vitamin B12 ≤200 pg/mL.
- •Ongoing participation in another interventional clinical trial or use of any other investigational medicinal product within five times the half-life.
- •Diagnosed to have MDS associated with del(5q) cytogenetic abnormality or MDS unclassifiable according to WHO 2016 classification or secondary MDS.
- •Participant is unwilling or in the opinion of the investigator the participant is unable to comply with the requirements of the protocol.
- •Is a participant of childbearing potential (POCBP) but does not agree to use at least 1 form of highly effective contraception from the time of signing the ICF until at least 60 days after the last dose of trial intervention (see Section 13.1 for details).
- •Participants of male birth who are fertile and who have partners of childbearing potential, who do not agree to use acceptable barrier contraception, that is, a male condom during the entire trial intervention period until at least 60 days after the last dose of trial intervention (see Section 13.1 for details).
- •If applicable, participant with a positive serum pregnancy test during the screening period or known to be pregnant or a lactating participant who does not agree to forego breastfeeding during the entire trial intervention period until at least 60 days after the last dose of trial intervention.
- •For Participants in France: Persons under court protection, persons not affiliated with a social security system, and protected adults (per applicable French law [Art. L. 1121-6, Art. L. 1121-8, Art. L. 1121-8-1]).
- •Known history of diagnosis of acute myeloid leukemia (AML).
- •Anemia due to any other known cause including but not limited to thalassemia; hypothyroidism; due to iron, vitamin B12, vitamin B6, zinc, or folate deficiencies; autoimmune or hereditary hemolytic anemia; any type of known clinically significant bleeding or sequestration or drug induced anemia, hemolytic anemia, or bleeding events.
- •Clinically significant cardiovascular disease defined as: a) New York Heart Association heart disease class III or IV. b) Fridericia corrected QT (QTcF) interval >500 milliseconds during screening. c) Uncontrolled arrhythmia, myocardial infarction, or unstable angina within 6 months before screening.
- •Known ejection fraction <35%, confirmed by a local echocardiogram performed during screening, or a previously performed echocardiogram if collected within 6 months before screening.
- •Medical history of thromboembolic events within 6 months before screening, including history of cerebrovascular accident (including ischemic, embolic, and hemorrhagic cerebrovascular accident), transient ischemic attack, deep venous thrombosis (DVT; including proximal and distal), pulmonary or arterial embolism, arterial thrombosis or other venous thrombosis. Participants with prior superficial thrombophlebitis are allowed.
- •Uncontrolled hypertension, defined as repeated elevations of systolic blood pressure of ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg despite adequate treatment.
- •Prior history of malignancies, other than MDS. Participants who are free of other malignant disease for ≥3 years and have completed treatment, including maintenance are allowed. Participants with a history or concurrent diagnosis of the following conditions are allowed if not requiring systemic therapy: a) Basal or squamous cell carcinoma of the skin; b) Carcinoma in situ of the cervix; c) Carcinoma in situ of the breast; and/or d) Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, node, metastasis [TNM] clinical staging system).
研究组 & 干预措施
ERYTHROPOIETIN
Comparator
干预措施: ERYTHROPOIETIN (Drug)
Elritercept
Test
干预措施: Elritercept (Drug)
结局指标
主要结局
Proportion of participants who are RBC-TI for any consecutive ≥12-week period from Cycle 1 Day 1 (C1D1) through Week 24 with concurrent mean Hgb increase ≥1.5 g/dL from baseline
Proportion of participants who are RBC-TI for any consecutive ≥12-week period from Cycle 1 Day 1 (C1D1) through Week 24 with concurrent mean Hgb increase ≥1.5 g/dL from baseline
次要结局
- Key Secondary Endpoint: Proportion of participants who are RBC-TI for any consecutive ≥16-week period from C1D1 through Week 24.
- Key Secondary Endpoint: Proportion of participants who are RBC-TI for any consecutive ≥12-week period from C1D1 through Week 24.
- Key Secondary Endpoint: Proportion of participants who are RBC-TI for a consecutive 24-week period from C1D1.
- For further details please refer to the Protocol
研究者
Alexander Vorog
Scientific
Takeda Development Center Americas Inc.
研究点 (57)
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