NCT04718844已完成1 期
A Randomised, Single-blind, Placebo-controlled, Phase 1, Single-ascending and Multiple-dose Study in Adult Subjects With Alpha/Beta-thalassaemia and Very Low- and Low-risk Myelodysplastic Syndrome to Investigate the Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Response of SLN124.
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 20
- 主要终点
- Incidence of treatment-emergent adverse events
研究概览
简要总结
This study will investigate the safety and tolerability of SLN124 in patients with Thalassaemia or patients with Very Low- and Low-risk Myelodysplastic Syndrome (MDS) after single ascending s.c. doses and multiple doses in healthy male and female subjects. Up to 7 cohorts of 56 patients with Thalassaemia and up to 7 cohorts of 56 patients with MDS will be enrolled. Each subject will receive single or multiple doses of SLN124 or placebo given by subcutaneous (s.c) injection.
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
- •Adult with alpha- or beta-thalassaemia or compound heterozygous haemoglobin E/beta-thalassaemia or adult with very low- or low-risk MDS according to the 2016 revision to the World Health Organisation classification.
- •All subjects must agree to adhere to appropriate contraception requirements.
- •Subjects must provide written informed consent and be able to comply with all study requirements.
- •Body mass index ≥18 kg/m2 and ≤35 kg/m2 at screening.
- •At least one of: a) Mean ferritin >250 μg/L based on a minimum of 2 measurements ≥1 week apart within 20 days before the planned dosing day, in the absence of active significant infection; b) Mean TSAT >40% measured on a minimum of 2 occasions ≥1 week apart within 20 days before the planned dosing day; c) Liver iron >3 mg Fe/g dry weight, measured according to local procedures.
- •Mean baseline haemoglobin concentration ≥5 g/dL and ≤11 g/dL, based on a minimum of 2 measurements ≥1 week apart, within 20 days before the planned dosing day.
- •Exclusion criteria
- •Adult with haemoglobin S/alpha-thalassaemia or haemoglobin S/beta-thalassaemia or adult with secondary MDS, i.e., MDS that is known to have arisen because of chemical injury or treatment with chemotherapy and/or radiation for another disease.
- •History of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc, or intolerance to s.c. injections.
- •Known infection with HIV, or active infectious hepatitis A, B, or C virus.
- •Any conditions which, in the opinion of the Investigator, would make the subject unsuitable for enrolment in the study or could interfere with the subject's participation in, or completion of the study.
- •History or clinical evidence of alcohol or illegal drug misuse within 2 years before screening.
- •Currently using ESA, or plan to use ESA at any point during the study.
- •Require daily treatment with 1 or more non-steroidal anti-inflammatory drugs during the study period. Paracetamol will be permitted for use as an antipyretic and/or analgesic.
- •Treatment, or change in treatment with prohibited medications as specified in the protocol
- •Treatment with ICT where the subject has not been on a stable dose for at least 8 weeks before screening or it is planned to initiate ICT therapy during the study.
- •Clinically significant cardiac disease
- •Clinically significant pulmonary disease
- •For subjects with thalassaemia:
- •Treatment, or change in treatment with prohibited medications as specified in the protocol
- •currently and anticipated to receiving more than 5 units of RBCs during the 24 weeks to 6 weeks period before first dose of study drug.
- •For subjects with very low / low-risk MDS:
- •Previous allogeneic or autologous stem cell transplantation.
- •Currently or planned to receive treatment with a corticosteroid for MDS within 8 weeks before screening.
- •Currently or planned to receive treatment with haematopoietic growth factors (e.g., eltrombopag, romiplostim) within 8 weeks before screening.
排除标准
- 未提供
研究组 & 干预措施
1.0mg/kg - Thalassaemia
Experimental
干预措施: SLN124 (Drug)
3.0mg/kg - Thalassaemia
Experimental
干预措施: SLN124 (Drug)
6.0mg/kg - Thalassaemia
Experimental
干预措施: SLN124 (Drug)
1.0mg/kg - Myelodysplastic Syndrome
Experimental
干预措施: SLN124 (Drug)
10.0mg/kg - Thalassaemia multi dose
Experimental
干预措施: SLN124 (Drug)
Placebo - Thalassaemia
Placebo Comparator
干预措施: Placebo (Drug)
Xmg/kg - Thalassaemia
Experimental
干预措施: SLN124 (Drug)
3.0mg/kg - Myelodysplastic Syndrome
Experimental
干预措施: SLN124 (Drug)
10.0mg/kg - Myelodysplastic Syndrome
Experimental
干预措施: SLN124 (Drug)
Xmg/kg - Myelodysplastic Syndrome
Experimental
干预措施: SLN124 (Drug)
3.0mg/kg - Thalassaemia multi dose
Experimental
干预措施: SLN124 (Drug)
Xmg/kg - Thalassaemia multi dose
Experimental
干预措施: SLN124 (Drug)
3.0mg/kg - Myelodysplastic Syndrome multi dose
Experimental
干预措施: SLN124 (Drug)
10.0mg/kg - Myelodysplastic Syndrome multi dose
Experimental
干预措施: SLN124 (Drug)
Xmg/kg - Myelodysplastic Syndrome multi dose
Experimental
干预措施: SLN124 (Drug)
Placebo - Thalassaemia multi dose
Placebo Comparator
干预措施: Placebo (Drug)
Placebo - Myelodysplastic Syndrome
Placebo Comparator
干预措施: Placebo (Drug)
Placebo - Myelodysplastic Syndrome multi dose
Placebo Comparator
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events
时间窗: Day 140
safety and tolerability will be reported separately following multi-dose administration.
次要结局
- Pharmacokinetic: area under the plasma concentration (AUC)(Day 84 and Day 140)
- Pharmacokinetic: apparent total clearance from plasma after s.c injection (CL/F)(Day 84 and Day 140)
- Pharmacodynamic biomarkers: Change in TSAT after s.c injection.(Day 84 and Day 140)
- Pharmacokinetic: peak plasma concentration (Cmax)(Day 84 and Day 140)
- Pharmacodynamic biomarkers: Change in hepcidin after s.c injection.(Day 84 and Day 140)
- Pharmacodynamic biomarkers: Change in serum iron after s.c injection.(Day 84 and Day 140)
- Pharmacodynamic biomarkers: Change in haemoglobin after s.c injection.(Day 84 and Day 140)
研究者
研究点 (20)
Loading locations...
相似试验
已完成
1 期
Study to Investigate Safety, Tolerability, PK and PD Response of SLN360 in Subjects With Elevated Lipoprotein(a)HyperlipidemiasDyslipidemiasElevated Lp(a)NCT04606602Silence Therapeutics plc70
撤回
1 期
Study in Beta-thalassaemia or Myelodysplastic Syndrome Patients to Investigate the Safety and Tolerability of SLN124Non-transfusion-dependent ThalassemiaLow Risk Myelodysplastic SyndromeNCT04176653Silence Therapeutics plc
已完成
1 期
A Multiple Ascending Dose Study of CSL112 in Healthy VolunteersHealthyNCT01281774CSL Limited36
已完成
2 期
A Study to Evaluate the Efficacy and Safety of ALS-L1023 in Subjects With NASHNonalcoholic SteatohepatitisNCT04342793AngioLab, Inc.60
终止
3 期
Efficacy and Safety Study of ALS-L1023 in Patients With Abdominal Obesity of Metabolic SyndromeAbdominal Obesity Metabolic SyndromeNCT01872182Hanmi Pharmaceutical Company Limited200