Phase II Study on the Efficacy, Safety, and Pharmacokinetics of HS-20106 in Patients With IPSS-R Very Low-risk, Low-risk, or Moderate-risk Myelodysplastic Syndrome (MDS) Anemia
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 176
- 试验地点
- 1
- 主要终点
- Proportion of participants who achieve modified 2006 International Working Group (IWG)Hematologic Improvement-Erythroid (HI-E) response
研究概览
简要总结
The purpose of this study is to evaluate the efficacy, safety, and pharmacokinetics of HS-20106 on anemia in patients with very low, low or intermediate risk MDS.
详细描述
Anemia is considered to be one of the most prevalent cytopenias in patients who have myelodysplastic syndromes, an umbrella term used to describe disorders relating to the ineffective production of red blood cells, white blood cells, and/or platelets. The goal of this study is to assess the efficacy, safety and PK of HS-20106 on anemia in Chinese patients with very low, low or intermediate risk MDS. Eligible subjects will be treated with HS-20106. Patients should be treated for at least 24 weeks in the core treatment period to assess their response to treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Diagnosis of MDS according to World Health Organization (WHO) classification that meets Revised International Prognostic Scoring System (IPSS-R) classification of very low, low, or intermediate risk disease（IPSS-R ≤ 3.5）.
- •< 5% blasts in bone marrow and < 1% blasts in peripheral blood.
- •Each cohort is defined as:
- •Cohort 1： In NTD participants, having received no red blood cell (RBC) transfusions within 16 weeks Hgb concentration between 60 and 100g/L.
- •Cohort 2： In LTB participants, having received an average of < 4 units of RBC transfused within 8 weeks (i.e., total blood transfused over 16 weeks/2) Hgb concentration between 60 and 100 g/L.
- •In HTB participants, having received an average of ≥ 4 units of RBC transfused within 8 weeks (i.e., total blood transfused over 16 weeks/2) Hgb concentration between 60 and 100 g/L.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (if related to anemia.
- •Females of child-bearing potential and sexually active males must agree to use effective methods of contraception.
排除标准
- •Chromosome 5q deletion, del (5q).
- •Anemia caused by other reasons, such as iron deficiency anemia, megaloblastic anemia, aplastic anemia, renal anemia or blood loss.
- •Diagnosis of secondary MDS (i.e., MDS known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases).
- •Prior treatment with azacitidine, decitabine, lenalidomide, luspatercept, or sotatercept.
- •Treatment within 4 weeks prior to C1D1 with:
- •Erythropoiesis stimulating agent (ESA) OR 2) Granulocyte colony-stimulating factor (G-CSF) OR 3) Granulocyte-macrophage colony-stimulating factor (GM-CSF)
- •Iron chelation therapy if initiated within 8 weeks prior to C1D
- •Vitamin B12 therapy if initiated within 8 weeks prior to C1D
- •Treatment with another investigational drug or device or approved therapy for investigational use < or = 4 weeks prior to C1D1, or if the half-life of the previous product is known, within 5 times the half-life prior to C1D1, whichever is longer.
- •Peripheral blood white blood cell count >13.0 x 10*9/L.
- •Neutrophil count < 1.0 x 10*9/L.
- •Platelet count > 450 x 10*9/L or < 30 x 10*9/L.
- •Transferrin saturation < 15%.
- •Ferritin < 15 μg/L.
- •Folate < 4.5 nmol/L (< 2.0 ng/mL).
- •Vitamin B12 < 148 pmol/L (< 200 pg/mL).
- •Estimated glomerular filtration rate (GFR) < 40 mL/min/1.73 m2 (as determined by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI].
- •Pregnant or lactating females
研究组 & 干预措施
HS-20106 Cohort 1
Part A: Non-transfusion dependent population
干预措施: HS-20106 (Drug)
HS-20106 Cohort 2
Part A: Transfusion-Dependent Population（low-transfusion burden (LTB) and high-transfusion burden (HTB)）
干预措施: HS-20106 (Drug)
结局指标
主要结局
Proportion of participants who achieve modified 2006 International Working Group (IWG)Hematologic Improvement-Erythroid (HI-E) response
时间窗: Week 1 through Week 24
* In NTD and LTB participants, response is defined as a mean hemoglobin (Hgb) increase of ≥ 15 g/L from Baseline during any consecutive 8-week period during the treatment period (in the absence of RBC transfusions) * In HTB participants, response is defined as a reduction by ≥ 4 units of RBCs transfused during any consecutive 8-week period on study compared with Baseline
次要结局
- HI-E Duration(Throughout the study period, assessed up to 48 weeks.)
- Time to HI-E(Week 1 through Week 24)
- Proportion of participants with RBC-TI ≥ 8 Weeks（cohort 2 only）(Week 1 through Week 24)
- Duration of TI response(Throughout the study period, assessed up to 48 weeks.)
- Time to RBC-TI ≥ 8 weeks(Week 1 through Week 24)
- The proportion of participants with progression to intermediate-risk (IPSS-R score > 3.5) and higher MDS or AML.(Week 1 through Week 24)
- Time to progression to intermediate-risk (IPSS-R score > 3.5) or higher MDS or AML.(Week 1 through Week 24)
- Incidence of adverse events (AEs) and serious adverse events (SAEs).(Throughout the study period, assessed up to 48 weeks.)
- Pharmacokinetic- AUC(Throughout the study period, assessed up to 48 weeks.)
- Pharmacokinetic- Cmax(Throughout the study period, assessed up to 48 weeks.)
- Antidrug antibodies (ADA)(Throughout the study period, assessed up to 48 weeks.)