NCT05568225终止2 期
A Phase 2 Open-Label Study to Evaluate Etavopivat for the Treatment of Anemia in Patients With Myelodysplastic Syndromes (MDS)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 24
- 主要终点
- Percentage of Participants With Hematologic Improvement- Erythroid (HI-E) Response for >=8 Weeks Within 24 Weeks of Etavopivat Treatment
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of etavopivat (FT-4202) for the treatment of anemia in adult patients with very low risk, low risk, or intermediate risk MDS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Patient has provided documented informed consent; the informed consent form (ICF) must be reviewed and signed by each patient prior to any study-related assessments/procedures being conducted.
- •Age ≥ 18 years at time of first dose.
- •Patients, if female and of childbearing potential, must agree to use acceptable methods of contraception and agree not to donate ova from study start to 90 days after the last dose of study drug, and who if male are willing to use acceptable methods of contraception and agree not to donate sperm, from study start to 90 days after the last dose of study drug.
- •Documented diagnosis of idiopathic/de novo MDS according to World Health Organization (WHO) classification that meets the IPSS-R classification of very low, low, or intermediate risk disease, and:
- •< 5% blasts in bone marrow based on local pathology review
- •< Intermediate risk cytogenetic abnormalities per IPSS-R
- •Anemia defined as:
- •Non-transfusion dependent (NTD): Subjects with mean Hb concentration < 10.0 g/dL of 2 measurements (1 performed within 3 days prior to Day 1 and the other performed 7 to 28 days prior to Day 1, not influenced by RBC transfusion within 7 days of measurement) and < 3 RBC transfusions for anemia in the prior 16 weeks before Day 1 of etavopivat dosing
- •Transfusion dependent (TD): Subjects having received ≥ 3 units of RBCs for the treatment of anemia within 16 weeks prior to Day 1
- •Serum erythropoietin level > 200 U/L, OR, if ≤ 200 U/L, subject is non-responsive, refractory, or intolerant to erythropoiesis-stimulating agents, or erythropoiesis-stimulating agents are contraindicated or unavailable.
- •ECOG performance status of ≤ 2
- •Subject is non-responsive, refractory, or intolerant to luspatercept, or luspatercept is contraindicated or not indicated.
- •No alternative treatment options are available and/or appropriate for the subject, at the discretion of the investigator.
- •Patient is willing and able to adhere to the study visit schedule and other protocol requirements
排除标准
- •[MDS History]
- •MDS associated with del 5q cytogenetic abnormality and known TP53 abnormality
- •Therapy-associated MDS (eg. t-MDS) that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases
- •Known history of acute myeloid leukemia (AML)
- •[Medical Conditions]
- •Female who is breast feeding or pregnant
- •Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
- •Absolute neutrophil count < 500/µL (0.5 x 10^9/L)
- •Platelet count < 50,000/µL (50 x 10^9/L) without transfusion support within 2 weeks
- •Hepatic dysfunction characterized by:
- •Alanine aminotransferase (ALT) > 5.0 × upper limit of normal (ULN)
- •Total bilirubin > 3.0 × ULN
- •History of cirrhosis
- •Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the local laboratory < 30 mL/min/1.73 m^2 ) or on chronic dialysis.
- •Patients with clinically significant and active bacterial, fungal, parasitic, or viral infection.
- •Patients with acute bacterial, fungal, parasitic, or viral infection requiring systemic therapy should delay Screening/ enrollment until active therapy has been completed.
- •Patients with acute viral infections without available therapies (eg, coronavirus disease 2019 [COVID-19]) should delay Screening/ enrollment until the acute infection has resolved.
- •Note: Infection prophylaxis is allowed.
- •Known human immunodeficiency virus (HIV) positivity
- •Active infection with hepatitis B virus (hepatitis B surface antigen [HepBsAg] and hepatitis B core antibody [HepBcAb] positive)
- •Active hepatitis C infection
- •History of malignancy, other than MDS, within the past 2 years prior to treatment Day 1 requiring systemic chemotherapy and/or radiation.
- •Patients with malignancy considered surgically cured are eligible (eg, non-melanoma skin cancer, carcinoma in situ of the cervix, or carcinoma in situ of the breast)
- •Patients with incidental histologic findings of prostate cancer (T1a or T1b) are eligible
- •History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:
- •Unstable angina pectoris or myocardial infarction or elective coronary intervention
- •Heart disease, heart failure as classified by the New York Heart Association classification 3 or higher, or significant arrhythmia requiring treatment,
- •Pulmonary fibrosis or pulmonary hypertension which are clinically significant ie, ≥ Grade 3 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (or higher)
- •Uncontrolled hypertension, defined as repeated elevation of diastolic blood pressure ≥ 100 mmHg despite adequate treatment
- •Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable).
- •[Prior/Concomitant Therapy]
- •Prior treatment with azacitidine (injectable or oral) or decitabine
- •Use of erythropoietin, other hematopoietic growth factor treatment or lenalidomide within 30 days of starting study treatment or anticipated need for such agents during the study.
- •Prior use of luspatercept:
- •NTD patients must not have received luspatercept within 30 days prior to Day 1 treatment
- •TD patients must not have received luspatercept within 16 weeks prior to Day 1 treatment
- •Receiving or use of concomitant medications that are strong inducers of cytochrome P450 (CYP)3A4/5 (see Appendix F) within 2 weeks of starting study treatment or anticipated need for such agents during the study.
- •Prior allogeneic or autologous stem cell transplant
- •Initiation of a new chelation therapy within 3 months before the first dose of study treatment.
- •[Prior/Concurrent Clinical Study Experience]
- •Participated in another clinical trial of an investigational agent (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational agent (or medical device).
- •[Other Exclusions]
- •Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent.
研究组 & 干预措施
Etavopivat 400 mg QD daily
Experimental
Non-transfusion dependent (NTD), Low transfusion burden (LTB) , and High transfusion burden (HTB) patients
干预措施: Etavopivat (Drug)
结局指标
主要结局
Percentage of Participants With Hematologic Improvement- Erythroid (HI-E) Response for >=8 Weeks Within 24 Weeks of Etavopivat Treatment
时间窗: From Baseline to Week 24
This outcome measure reported on the combined incidence of NTD, LTB and HTB in terms of (HI-E) response for \>=8 weeks duration in participants with myelodysplastic syndromes (MDS) within 24 weeks. The participants were allocated to the following arms which were defined as: 1) NTD: \>=1.5 grams per deciliter (g/dL) increase in haemoglobin (Hb) from baseline maintained \>=8 consecutive weeks and no transfusion of RBC units for anemia over a continuous 8-week treatment period; 2) LTB: absence of any transfusion for \>=8 consecutive weeks; and 3) HTB: reduction by \>=50 percent (%) of RBC units for \>=8 consecutive weeks.
次要结局
- Percentage of Participants With Hematologic Improvement-Erythroid (HI-E) Response for =>8 Weeks Within 16 and 48 Weeks of Etavopivat(48 weeks)
- Percentage of Participants With Hematologic Improvement- Erythroid (HI-E) Response for =>16 Weeks Within 24 and 48 Weeks of Etavopivat(48 weeks)
- Number of All Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Related to Etavopivat(From baseline up to 48 weeks)
- Overall Response Rate(Up to 48 weeks)
- Number of Premature Discontinuations, Dose Interruptions, and Dose Reductions(Within 48 weeks)
- Percent Change From Baseline in RBC Transfusion Independence for =>8 Weeks in Participants With LTB or HTB at Study Entry(Up to 48 weeks)
- Duration of Response(Up to 48 weeks)
- Reduction in RBC Transfusions for >=8 Weeks in Participants With LTB or HTB at Study Entry(Up to 48 weeks)
- Change From Baseline in Neutrophils and/or Platelets Counts(Baseline (week 0), week 48)
- Overall Survival(Within 48 weeks)
- Decrease in Ferritin and Transferrin Saturation (TSAT)(Up to 48 weeks)
- Decrease in Iron Chelation Therapy(up to 48 weeks)
- Etavopivat Plasma Concentrations(Weeks 1 and 4 pre-dose, post-dose 1, 2, 4, 6 hours.Week 2 and EOT (week 48):pre-dose, post-dose 1, 2 hours)
- RBC 2,3-diphosphoglycerate (2,3-DPG) and Adenosine Triphosphate (ATP) Levels Over Time(Within 48 weeks)
研究者
研究点 (24)
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