A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Investigating the Efficacy and Safety of Roxadustat (FG-4592) for Treatment of Anemia in Patients With Lower Risk Myelodysplastic Syndrome (MDS) With Low Red Blood Cell (RBC) Transfusion Burden (LTB)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- FibroGen
- 入组人数
- 184
- 试验地点
- 4
- 主要终点
- OL and OL High-EPO Components: Number of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) ≥8 Weeks (≥56 Consecutive Days) Since First Dose in the First 28 Weeks of Treatment
研究概览
简要总结
The purpose of this study is to determine whether FG-4592 is safe and effective in the treatment of anemia in participants with lower risk MDS and low red blood cell transfusion burden.
详细描述
This study includes an Open-Label Lead in, a Double-Blind component, and an Open-Label High Erythropoietin component. There is a screening period of up to 42 days followed by a treatment period of 52 weeks and a 4-week end of treatment assessment.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 MDS classified by the International Prognostic Scoring System - Revised (IPSS-R) as very low, low or intermediate risk with <5% bone marrow blasts. There is no minimum time from diagnosis to registration/randomization except to allow for proper IPSS-R classification to be made (within 16 weeks prior to randomization), and to show transfusion dependence for participants in both portions of the study.
- •RBC transfusion of either 2-4 pRBC units during the 8 weeks prior to registration/randomization or 1 pRBC in two consecutive periods of 8 weeks within the 16 weeks prior to registration/randomization. Open-Label Lead-in participants only, the requirement to demonstrate transfusion dependence can also be met by a Principal Investigator starting this particular participant on pRBC transfusion during the screening period.
- •No restriction on prior use of recombinant erythropoietins or analogues (erythropoiesis-stimulating agents [ESAs]), except no ESA use within 8 weeks prior to Day 1 registration/randomization.
- •Hemoglobin (Hb) ≤10.0 grams/deciliter (g/dL) during screening
- •Eastern Cooperative Oncology Group (ECOG) of 0-2 at screening
排除标准
- •Diagnosis of secondary MDS associated with prior chemotherapy, extensive radiation therapy (>25% of bone marrow reserve), and or/other significant chemical or radiation exposure
- •Significant myelofibrosis (>2+ fibrosis)
- •MDS associated with 5q(del) cytogenetic abnormality
- •Screen serum erythropoietin level > 400 milli-international units (mIU)/milliliter (mL) • Clinically significant anemia, as determined by the investigator, due to non-MDS etiologies such as iron deficiency, vitamin B12 or folate deficiency, autoimmune or hereditary hemolysis or anemia or hemorrhage or hereditary anemia such as sickle cell anemia or thalassemia.
研究组 & 干预措施
Roxadustat
Open-label, lead-in: Participants will receive sequential escalating roxadustat doses (1.5 milligrams/kilograms [mg/kg], 2.0 mg/kg and 2.5 mg/kg), three times a week (TIW) based upon their actual weight at the randomization visit to identify the starting dose for double-blind period.
Double-blind: Participants will receive roxadustat 2.5 mg/kg TIW based upon their body weight for a duration of 52 weeks.
Open-label: Participants with high serum erythropoietin levels (>400 milli-international units [mIU]/milliliter [mL] mIU/mL) will receive roxadustat 2.5 mg/kg TIW based upon their body weight for a duration of 52 weeks.
干预措施: Roxadustat (Drug)
Placebo
Double-blind: Participants will receive placebo matching to roxadustat for a duration of 52 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
OL and OL High-EPO Components: Number of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) ≥8 Weeks (≥56 Consecutive Days) Since First Dose in the First 28 Weeks of Treatment
时间窗: 28 weeks
The RBC TI was defined as the absence of any intravenous (IV) RBC transfusion (packed cell or whole blood) during any consecutive 56 days during the treatment period. Data presented is for number of participants with RBC TI ≥8 weeks (≥56 consecutive days) since first dose in the first 28 weeks of treatment.
DB Component: Number of Participants Who Achieved RBC TI ≥56 Consecutive Days Since First Dose in the First 28 Weeks of Treatment
时间窗: 28 weeks
RBC TI was defined as the absence of any IV RBC transfusion (packed cell or whole blood) during any consecutive 56 days during the treatment period. Data presented is for number of participants with RBC TI ≥56 consecutive days since first dose in the first 28 weeks of treatment.
次要结局
- DB Component: Number of Participants Who Achieved TI ≥56 Consecutive Days Since First Dose in 52 Weeks of Treatment(52 weeks)
- DB Component: Number of Participants Who Achieved ≥50% Reduction From Baseline in Number of pRBC Transfusions Over 8 Weeks(Baseline up to Week 8)
- DB Component: Mean Change From Baseline in the Patient-Reported Outcomes Measurement Information System-Short Form (PROMIS-SF) v2.0 Physical Function (PF) 10b Score at Week 9(Baseline, Week 9)
- DB Component: Mean Change From Baseline in the PROMIS-SF v1.0 Fatigue 13a Score at Week 9(Baseline, Week 9)
- OL and OL High-EPO Components: Number of Participants Who Achieved TI ≥50% Reduction From Baseline in Number of Packs of Red Blood Cells (pRBC) Transfusions Over 8 Weeks(Baseline up to Week 8)
- DB Component: Number of Participants Who Achieved TI ≥56 Consecutive Days Anytime During the Study(Baseline up to Week 56)
- DB Component: Cumulative Number of Participant Exposure Weeks (PEW) of TI Over the First 28 Weeks of Treatment(28 weeks)
- DB Component: Change From Baseline in Number of pRBC Packs Transfused Over the First 28 Weeks of Treatment(Baseline, Week 28)
- DB Component: Number of Participants Who Achieved TI ≥20 Consecutive Weeks During the Study(Baseline up to Week 56)
- DB Component: Mean Change From Baseline in the European Quality of Life Five Dimensional Five Level Health Questionnaire (EQ-5D-5L) Visual Analogue Scale Score at Week 9(Baseline, Week 9)