A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Nomlabofusp in Adolescents and Children With Friedreich's Ataxia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Number of AEs, TEAEs, related TEAEs, Grade 3/4 TEAEs, and SAEs
研究概览
简要总结
The goal of this clinical trial is to evaluate the safety and tolerability of nomlabofusp (CTI-1601) in adolescents and children with Friedreich's ataxia (FRDA).
详细描述
This is a randomized, double-blind, placebo-controlled study evaluating a weight-based dose of nomlabofusp versus placebo in adolescents and children with FRDA. The study will consist of at least two cohorts with at least 12 to 15 participants in each cohort. Participants will be dosed once daily (QD) for 7 days.
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
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject has genetically confirmed diagnosis of FRDA manifested by homozygous GAA repeat expansions, with repeat sizing (if available) included on the diagnosis report.
- •Male or female subjects ≥ 2 to < 18 years of age at screening.
- •Subjects must weigh ≥ 10.0 kg.
- •Subject must be able to traverse a distance of 25 feet with or without some assistive device (e.g., cane, walker, crutches, self-propelled wheelchair) and meet the following requirements:
- •Be able to sit upright with thighs together and arms crossed without requiring support on more than 2 sides;
- •Be able to transfer from bed to chair independently or with assistance if, in the opinion of the investigator, the degree of physical disability does not result in undue risk to the subject while participating in the study; and
- •Perform basic age-appropriate daily care, such as feeding themselves and personal hygiene, with minimal assistance.
排除标准
- •Subjects who are confirmed as compound heterozygous (GAA repeat expansion on only 1 allele) for FRDA.
- •Subject has any condition, disease, or situation, including a cardiac condition or disease, that in the opinion of the investigator could confound the results of the study or put the subject at undue risk, making participation inadvisable.
- •Subjects currently receiving or having received omaveloxolone within 30 days prior to Screening.
研究组 & 干预措施
Nomlabofusp
Subcutaneous injection of 0.8 mg/kg, with a maximum dose of 50 mg, once daily for 7 days
干预措施: Nomlabofusp (Drug)
Placebo
Subcutaneous injection once daily for 7 days
干预措施: Placebo (Drug)
结局指标
主要结局
Number of AEs, TEAEs, related TEAEs, Grade 3/4 TEAEs, and SAEs
时间窗: Up to 72 days (including screening)
Number
Number of subjects with ISRs
时间窗: Up to 37 days
Number
Change from baseline in electrocardiogram (ECG) parameter - heart rate (HR)
时间窗: Baseline, Day 7
Number
Change from baseline in electrocardiogram (ECG) parameter - PR interval
时间窗: Baseline, Day 7
Number
Change from baseline in electrocardiogram (ECG) parameter - QRS complex
时间窗: Baseline, Day 7
Number
Change from baseline in electrocardiogram (ECG) parameter - QT interval
时间窗: Baseline, Day 7
Number
Change from baseline in electrocardiogram (ECG) parameter - QTcF (Corrected QT Interval)
时间窗: Baseline, Day 7
Number
Change from baseline in echocardiogram (ECHO) parameter - ejection fraction (EF)
时间窗: Baseline, Day 7
Number
Change from baseline in echocardiogram (ECHO) parameter - left ventricular end-diastolic volume (LV EDV)
时间窗: Baseline, Day 7
Number
Change from baseline in echocardiogram (ECHO) parameter - left ventricular end-systolic volume (LV ESV)
时间窗: Baseline, Day 7
Number
Change from baseline in echocardiogram (ECHO) parameter - relative wall thickness (RWT)
时间窗: Baseline, Day 7
Number
Change from baseline in echocardiogram (ECHO) parameter - left ventricular mass (LVM)
时间窗: Baseline, Day 7
Number
Change from baseline in echocardiogram (ECHO) parameter - left ventricular posterior wall thickness
时间窗: Baseline, Day 7
Number
Change from baseline in echocardiogram (ECHO) parameter - septal wall thickness
时间窗: Baseline, Day 7
Number
Change from baseline in echocardiogram (ECHO) parameter - mitral valve inflow Doppler
时间窗: Baseline, Day 7
Number
Change from baseline in echocardiogram (ECHO) parameter - tissue Doppler
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - sodium
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - potassium
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - glucose
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - blood urea nitrogen
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - creatinine
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - calcium, chloride
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - phosphorus
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - total protein
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - total CO2
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - albumin
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - AST
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - ALT
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - GGT
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - ALP
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - total bilirubin
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - uric acid
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - HbA1c
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - hemoglobin
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - hematocrit
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - RBC count
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - RDW
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - MCV
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - MCH
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - platelet count
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - WBC count
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - ANC
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - Eosinophils
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - Monocytes
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - Basophils
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - Lymphocytes
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - Bands
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - Neutrophils
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - Cholesterol
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - HDL cholesterol
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - LDL cholesterol
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - Triglycerides
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - very low-density lipoprotein cholesterol
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - pH
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - protein
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - blood
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - ketones
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - bilirubin
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - urobilinogen
时间窗: Baseline, Day 7
Number
Number of subjects with suicidal ideation, suicidal behavior, and suicidal ideation or behavior based on the Columbia Suicide Severity Rating Scale (C-SSRS)
时间窗: Up to 72 days (including screening)
Number
Change from baseline in clinical laboratory assessment - nitrites
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - leukocyte esterase
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - color
时间窗: Baseline, Day 7
Number
Change from baseline in clinical laboratory assessment - specific gravity
时间窗: Baseline, Day 7
Number
Change from baseline in pulse rate
时间窗: Baseline, Day 7
Number
Number of subjects with abnormal physical examinations
时间窗: Up to 72 days (including screening)
Number
Number of subjects who discontinue treatment and/or study
时间窗: Up to 37 days
Number
次要结局
- AUC0-last(Days 1, 7)
- Cmax(Days 1, 7)
- Tmax(Days 1, 7)
- Ctrough(Days 1, 7)
- Change from baseline in FXN concentrations normalized to total protein observed in buccal cells collected from cheek swabs(Baseline, Day 7)