SPL84 在囊性纤维化患者中的安全性、耐受性、药代动力学和初步疗效
2026年5月11日 更新者：SpliSense Ltd.
一项针对携带 3849 +10 Kb C->T 突变的囊性纤维化患者进行的 2a 期随机、安慰剂对照、双盲多剂量递增研究，旨在评估 SPL84 的安全性、耐受性、药代动力学和初步疗效
该临床试验的目的是了解药物 SPL84 对于成年囊性纤维化 (CF) 患者是否安全。 它还将了解该药物是否可以治疗具有特定突变的 CF。
本研究的目的是：
- 测试多剂量研究药物 SPL84 的安全性和有效性
- 测试身体如何处理多剂量的药物
研究人员将药物 SPL84 与安慰剂（一种不含药物的相似物质）进行比较，看看药物 SPL84 是否安全以及是否能有效治疗 CF。
参与者将：
每周吸入药物 SPL84 或安慰剂，持续 9 周，每月 17.5 周内约前往诊所 14 次进行检查和测试
研究概览
研究类型
介入性
注册 (估计的)
64
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
-
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California
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Los Angeles、California、美国、90033
- 招聘中
- University of Southern California
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接触：
- Study Coordinator
- 电话号码：+1 323 409 5383
- 邮箱：lynn.fukushima@med.usc.edu
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Colorado
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Denver、Colorado、美国、80206
- 招聘中
- National Jewish Health
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接触：
- Site Manager
- 电话号码：303-270-2517
- 邮箱：wilsona@njhealth.org
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Massachusetts
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Boston、Massachusetts、美国、02115
- 尚未招聘
- Boston Children's Hospital
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接触：
- Julia Giancola
- 电话号码：617-355-4171
- 邮箱：Julia.Giancola@childrens.harvard.edu
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-
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
不
描述
纳入标准：
- 诊断CF和引起突变的两种CF； CF 跨膜电导调节 (CFTR) 基因（纯合子或复合杂合子）中的一个等位基因发生 3849+10 Kb C->T 突变。 需要来自经过认证的基因实验室的源文件。
- 体重指数 (BMI) ≥ 17 kg/m2。
- 筛查时预测 FEV1 为 40-90%。
- 根据参与者的报告，在筛选前至少 180 天（6 个月）不吸烟或吸电子烟。
排除标准：
- 在首次给药后 30 天内使用 Kalydeco、Orkambi、Symdeko/Symkevi 或 Trikafta/Kaftrio，并进行研究干预。
- 在首次给药后 30 天内使用任何研究药物（SPL84 除外）或装置并进行研究干预。
- 在筛选前的最后 6 个月内连续 3 个月使用全身类固醇，或在筛选前的最后一个月使用全身类固醇。 使用超过 1 毫克的吸入类固醇。
- 使用 CF 药物，例如 筛查前 28 天应采用稳定的吸入抗生素、dornase alfa (Pulmozyme)、高渗盐水和物理疗法；那些服用吸入性抗生素进行预防的参与者必须在首次接受研究干预之前至少 90 天稳定地服用这些药物。
- 任何急性感染，包括急性上呼吸道或下呼吸道感染、肺部病情加重、肺部疾病治疗的改变或任何非 CF 相关疾病，导致在研究干预的首次给药前 14 天内开始任何新疗法。
- 第 1 天前 90 天内咯血超过 30 mL，或在研究干预下首次给药后 6 个月内因咯血住院。
- 以临床上显着的肝硬化和/或记录的门静脉高压为特征的肝病。
- 任何器官移植史。
- 给药前 4 周内记录有冠状病毒病 (COVID-19) 感染情况。
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：顺序分配
- 屏蔽：双倍的
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Safety and Tolerability of SPL84 as evaluated by number of subjects with at least one treatment-related adverse event (AE) or serious adverse event (SAEs)
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
Incidence, nature, and severity of AEs and SAEs
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
|
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal heart rate
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
|
|
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal respiratory rate
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
|
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Safety and Tolerability of SPL84 as assessed by number of participants with abnormal systolic and diastolic blood pressure
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
|
|
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal oximetry
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
|
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Safety and Tolerability of SPL84 as assessed by number of participants with abnormal temperature
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
|
|
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal hematology lab test results
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
|
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Safety and Tolerability of SPL84 as assessed by number of participants with abnormal biochemistry lab test results
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
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|
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal urinalysis lab test results
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
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Safety and Tolerability of SPL84 as assessed by number of participants with abnormal electrocardiogram (ECG) parameters
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
using an ECG machine that automatically calculates heart rate and measure PR, QRS, QT, and QTc intervals
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
|
Safety and Tolerability of SPL84 as assessed by number of participants with abnormal physical examination findings
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
Complete physical examinations include general appearance, head, ears, eyes, nose, throat, thyroid, chest (heart, lungs), abdomen, skin, neurological, extremities, back, neck, musculoskeletal, and lymph nodes.
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Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
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Safety and Tolerability of SPL84 as assessed by number of participants with abnormal pulmonary function tests results
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
Pulmonary function tests will be performed according to the American Thoracic Society (ATS)/European Respiratory Society (ERS) and forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and forced mid-expiratory flow (FEF25-75) will be measured
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
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Safety and Tolerability of SPL84 as assessed by number of participants with abnormal immunogenicity results
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
assessment of anti-SPL84 antibodies will be performed both in serum and sputum
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Characterization of pharmacokinetics (PK) of SPL84: maximum serum concentration (Cmax)
大体时间：Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
|
Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
|
|
|
Characterization of PK of SPL84: Time to Cmax (Tmax)
大体时间：Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
|
Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
|
|
|
Characterization of PK of SPL84: terminal elimination half-life (t1/2)
大体时间：Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
|
Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
|
|
|
Characterization of PK of SPL84: Area under the curve to the final sample (AUC0-t)
大体时间：Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
|
Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
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Characterization of PK of SPL84: Area under the curve to infinity (AUC0-∞)
大体时间：Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
|
Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
|
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Characterization of PK of SPL84: Apparent clearance (CL/F)
大体时间：Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
|
Cohort 1-3: Predose and 15 and 30 minutes and 1, 2, 4, 6, 8, and 24 hours postdose on Day 1 and Day 57; predose on Days 8 and 29; Days 64 and 87; Cohort 4: Predose and 1, 3, and 6 hours post dose on Days 1 and 78
|
|
|
Characterization of excretion of SPL84: concentration of SPL84 in urine
大体时间：Day 1 through Day 87 (Cohort 1-3) or Day 85 (Cohort 4)
|
Day 1 through Day 87 (Cohort 1-3) or Day 85 (Cohort 4)
|
|
|
Efficacy of SPL84 as assessed by change from baseline in percent predicted FEV1
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
Pulmonary function tests will be performed according to the ATS/ERS
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
|
Efficacy of SPL84 as assessed by change from baseline in percent predicted FEF25-75
大体时间：Day 1 to Day 87 (Cohort 1-3) or Day 108 (Cohort 4)
|
Day 1 to Day 87 (Cohort 1-3) or Day 108 (Cohort 4)
|
|
|
Efficacy of SPL84 as assessed by change from baseline in Cystic Fibrosis Questionnaire-Revised Respiratory Symptom Score
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
The score for is standardized on a 0- to 100-point scale on which higher scores represent a higher quality of life
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
|
Efficacy of SPL84 as assessed by change from baseline in body weight
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
|
|
Preliminary efficacy of SPL84 as assessed by change from baseline of antibiotic treatment (Cohort 1-3 only)
大体时间：Day 1 through Day 87
|
Day 1 through Day 87
|
|
|
Cohort 1-3: Safety and Tolerability of SPL84 as assessed by number of participants with abnormal sputum microbiology results Cohort 4: Exploratory efficacy of SPL84 as assessed by number of participants with change in abnormal sputum microbiology result
大体时间：Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
Sputum microbiology will be performed with a microbiology based assay; organism growth will be identified.
|
Day 1 through Day 87 (Cohort 1-3) or 108 (Cohort 4)
|
|
Exploratory efficacy of SPL84 as assessed by number of participants with change in Lung Clearance Index at 2.5% of starting concentration (LCI2.5)
大体时间：Day 1 to Day 85
|
Measured using multiple breath washout (at select study sites only)
|
Day 1 to Day 85
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2024年6月24日
初级完成 (估计的)
2027年10月1日
研究完成 (估计的)
2027年12月31日
研究注册日期
首次提交
2024年5月15日
首先提交符合 QC 标准的
2024年5月20日
首次发布 (实际的)
2024年5月24日
研究记录更新
最后更新发布 (实际的)
2026年5月14日
上次提交的符合 QC 标准的更新
2026年5月11日
最后验证
2026年5月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.