A Phase II, Open-label Study to Investigate the Pharmacokinetics and Safety of Risdiplam in Infants with Spinal Muscular Atrophy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 8
- 试验地点
- 10
- 主要终点
- Plasma concentration of risdiplam and metabolite(s) as applicable at specified timepoints
研究概览
简要总结
To characterize the risdiplam PK profile and to evaluate the safety of risdiplam
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Follow-up
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •Male or female newborn infant aged <20 days at first dose.
- •Newborn infants with genetic diagnosis of 5q-autosomal recessive SMA or newborn infants identified as positive for SMA via newborn screening or via prenatal testing.
- •Gestational age equal to or greater than 37 weeks.
- •Receiving adequate nutrition and hydration at the time of screening.
- •Adequately recovered from any acute illness at baseline and considered well enough to participate in the study.
- •Parent/caregiver is willing to consider nasogastric, nasojejunal, or gastrostomy tube placement during the study to maintain safe hydration, nutrition, and treatment delivery, if recommended by the investigator.
排除标准
- •Presence of clinical symptoms or signs consistent with SMA Type
- •In the opinion of the investigator, inadequate venous or capillary blood access for the study procedures.
- •Systolic blood pressure or diastolic blood pressure or heart rate abnormalities or presence of clinically relevant electrocardiogram (ECG) abnormalities.
- •The infant (or the person breastfeeding the infant) taking any of the following: any inhibitor of CYP3A4 taken within 2 weeks (or within 5 times the elimination half-life, whichever is longer) prior to dosing, any inducer of CYP3A4 taken within 4 weeks (or within 5 times the elimination half-life, whichever is longer prior to dosing, and/or use of any multidrug and toxin extrusion (MATE) substrates taken within 2 weeks (or within 5 times the elimination half-life, whichever is longer) prior to dosing.
- •Concurrent or previous administration of nusinersen or onasemnogene abeparvovec.
- •Clinically significant abnormalities in laboratory test.
结局指标
主要结局
Plasma concentration of risdiplam and metabolite(s) as applicable at specified timepoints
Plasma concentration of risdiplam and metabolite(s) as applicable at specified timepoints
AUC
AUC
Concentration at the end of a dosing interval to assess steady-state
Concentration at the end of a dosing interval to assess steady-state
Other PK parameters as appropriate
Other PK parameters as appropriate
Risdiplam free fraction
Risdiplam free fraction
Incidence and severity of adverse events, with severity determined according to the NCI CTCAE v5.0
Incidence and severity of adverse events, with severity determined according to the NCI CTCAE v5.0
Incidence and severity of serious adverse events
Incidence and severity of serious adverse events
Incidence of treatment discontinuation due to adverse events
Incidence of treatment discontinuation due to adverse events
Incidence of abnormal laboratory values
Incidence of abnormal laboratory values
Incidence of abnormal ECG values
Incidence of abnormal ECG values
Vital signs abnormalities, including body temperature, systolic and diastolic blood pressure, heart rate, respiratory rate
Vital signs abnormalities, including body temperature, systolic and diastolic blood pressure, heart rate, respiratory rate
Physical examination, including detailed examination of the skin and mouth
Physical examination, including detailed examination of the skin and mouth
次要结局
未报告次要终点
研究者
Head of CTRM Clinical Trial Regulatory Management, Product Development Regulatory
Scientific
F. Hoffmann-La Roche AG