Open-Label, Non-controlled, Single Ascending Dose Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Exploratory Efficacy of KTP-001 in Subjects With Lumbar Disc Herniation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 10
- 主要终点
- Safety Assessed by Adverse Events, Magnetic Resonance Imaging (MRI), X-ray Imaging, Physical Examination, Neurologic Examination and Vital Signs
研究概览
简要总结
The purpose of this study is to evaluate the safety and exploratory efficacy of KTP-001 in subjects with lumbar disc herniation.
详细描述
This study was a first-in-human, open-label, non-controlled single ascending dose study of KTP-001 in male and female subjects between the ages of 30 and 70 years with a single herniated lumbar disc. After obtaining informed consent, subjects were evaluated during a screening period of no more than 3 weeks (21 days). This study was conducted in 10 centers in the US.
Subjects that met all screening requirements and inclusion criteria and none of the exclusion criteria were enrolled into the study. Overall, 24 subjects were enrolled and treated: 6 subjects in each cohort. Cohort 1 received a 5 μg/disc dose of KTP-001 by intradiscal injection. Following administration of study drug, subjects were confined to the study center for 24 hours to collect data for safety and efficacy measures and collect blood samples for safety, PK evaluation, exploratory PD and anti-KTP-001 antibody and then returned for further assessments at various intervals from weeks 1 through to month 24.
After all subjects in Cohort 1 had received study drug, safety measures were evaluated by a Data and Safety Monitoring Board (DSMB) to determine whether to escalate KTP-001 administration to the next dose level. If appropriate, Cohort 2 subjects received 15 μg/disc of KTP-001, Cohort 3 subjects received 50 μg/disc of KTP-001, and Cohort 4 subjects received 150 μg/disc of KTP-001 by intradiscal injection. All safety, PK, and exploratory efficacy assessments were performed for the subjects in the subsequent cohorts as were performed for Cohort 1.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject has had a single contained or noncontained (extruded) lumbar disc herniation (L3-L4, L4-L5 or L5-S1) diagnosed by clinical symptoms and/or physical findings and confirmed by MRI.
- •Subject has leg pain with a documented positive straight leg raise (SLR) test or femoral stretch test (FST).
- •Subject has experiences herniated disc symptoms for at least 6 weeks prior to the study without relief with pain medications and other therapies.
- •Subject has a BMI of 18 to 35 kg/m2
排除标准
- •Subject has a sequestered lumbar disc herniation or intrathecal herniation confirmed by MRI
- •Subject has two or more symptomatic lumbar disc herniations
- •Previous intradiscal therapeutic intervention or has had any lumbar surgery
- •Presence of lumbar spine disease and/or deformity other than a lumbar disc herniation
- •Active smoker or is unable to abstain from tobacco use for 2 weeks prior to study injection
- •Subject has a history or presence of significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or psychiatric disease
研究组 & 干预措施
Cohort 1
one time 5 μg/disc dose of KTP-001 by intradiscal injection
干预措施: KTP-001 (Drug)
Cohort 2
one time 15 μg/disc dose of KTP-001 by intradiscal injection
干预措施: KTP-001 (Drug)
Cohort 3
one time 50 μg/disc dose of KTP-001 by intradiscal injection
干预措施: KTP-001 (Drug)
Cohort 4
one time 150 μg/disc dose of KTP-001 by intradiscal injection
干预措施: KTP-001 (Drug)
结局指标
主要结局
Safety Assessed by Adverse Events, Magnetic Resonance Imaging (MRI), X-ray Imaging, Physical Examination, Neurologic Examination and Vital Signs
时间窗: 24 months
Any clinically significant changes were recorded as adverse events. They are described in the adverse events section of the results. AEs related to MRI, X-ray Imaging, Physical examination, and Neurologic examination are considered as adverse events of special interest (AESI). A treatment-emergent AE (TEAE) was defined as an AE that was not present prior to treatment with study drug, but appeared following treatment or was present at treatment initiation but worsened in severity during treatment.
Number of Participants With Change in 12-lead Electrocardiogram (ECG) and Clinical Laboratory Tests (CLT)
时间窗: 13 weeks
Assessment of the number of participants with change in 12-lead ECG and CLT were assessed from baseline, 24 hours and 13 weeks.
次要结局
- Number of Participants Serum Concentrations of KTP-001 Below the Limit of Quantification (BLQ)(13 weeks)
- Number of Participants With Anti-KTP-001 Antibody(13 weeks)