Phase 1b Single Ascending and Multiple Dose First-in-man Study in Adult Patients With Non-transfusion-dependent Beta-thalassaemia or Low Risk Myelodysplastic Syndrome to Investigate the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Response of SLN124
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 5
- 主要终点
- clinical chemistry, haematology, urinalysis, liver function tests (included ALT, AST, GGT) will be measured from baseline to post dose follow up
研究概览
简要总结
The primary purpose of this study is to determine the safety and tolerability of SLN124 for the treatment of non-transfusion-dependent (NTD) β-thalassaemia and low risk myelodysplastic syndrome.
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
- Double (Participant, Investigator)
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
- •Age ≥ 18yrs; BMI 18-35 kg/m2
- •β-thalassaemia intermedia or compound heterozygous HbE/β-thalassaemia
- •Non-transfusion dependent: ≤ 5 units red cells in last 6 months and transfusion-free for ≥8 weeks
- •Hb between 5 & 11 g/dL
- •Ferritin > 250 µg/L and /or liver iron ≥ 3mg Fe/g dry weight and TSAT >40%
排除标准
- •Haemoglobin S/β-thalassaemia, homozygous β-0 thalassaemia or α thalassaemia
- •ALT/AST > 1.5 x upper limit normal or cirrhosis
- •eGFR < 60 mL/min/1.73m2
- •Platelets <100 or > 1000 x 109/L
- •Untreated B12/folate deficiency
- •Iron chelation therapy unless stable for ≥8 weeks
- •Daily NSAID, therapeutic dose anticoagulant, ESA ≤12 weeks or stable dosing of hydroxyurea ≤ 6 months
- •Significant cardiac disease (MI in 6 months, NYHA class III-IV heart failure, long QT)
- •HIV or active hepatitis B/C or malignancy within 5 year
研究组 & 干预措施
Placebo
干预措施: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo (Drug)
0.3 mg/kg
干预措施: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo (Drug)
1.0 mg/kg
干预措施: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo (Drug)
3.0 mg/kg
干预措施: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo (Drug)
10.0 mg/kg
干预措施: SLN124 is a GalNAc conjugated double stranded fully modified siRNA. Sodium chloride 0.9% w/v is used as Placebo (Drug)
结局指标
主要结局
clinical chemistry, haematology, urinalysis, liver function tests (included ALT, AST, GGT) will be measured from baseline to post dose follow up
时间窗: Up to two months
# of participants with all AEs as assessed by CTCAE V4.0 included injection site reaction, will be measured from baseline to post dose follow up
时间窗: Up to two months
12 lead electrocardiogram parameters included PR, QTcF and QTcB will be measured from baseline to post dose follow up
时间窗: Up to two months
height, weight, blood pressure, heart rate, respiration rate and temperature will be measured from baseline to post dose follow up
时间窗: Up to two months
次要结局
- Biomarkers will be measured from baseline to post dose follow up(Up to two months)
- Pharmacokinetic of SLN124 in plasma from baseline to post dose follow up(Up to two months)