A Phase 1, Open-label, Multi-part Study to Evaluate the Safety, Tolerability, Kinetics, Biodistribution, and CNS Signal of the Positron Emission Tomography Ligand 11C-BMS-986196 in Healthy Participants After Intravenous Administration and to Evaluate the Safety, Tolerability, Kinetics, and CNS Signal Repeatability of 11C-BMS-986196 After Repeat Intravenous Administration in Participants With Multiple Sclerosis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Number of Participants With Clinically Significant Changes in Electrocardiograms.
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, kinetics, biodistribution and central nervous system signal of 11C-BMS-986196 after intravenous (IV) administration in healthy participants and after repeat IV administration in participants with multiple sclerosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For Parts A & B:
- •Body mass index (BMI) of 18 to 34 kg/m2, inclusive, and total body weight ≥ 50 kg
- •Documentation of normal Allen's test result at Screening and on PET scanning days in the arm that will be used for arterial line placement
- •For Part A only:
- •Healthy male and female participants without clinically significant deviation from normal in medical history, physical examination (PE), electrocardiograms (ECGs), and clinical laboratory determinations
- •For Part B only:
- •Male or female participant diagnosed with MS according to the 2017 revisions of the McDonald diagnostic criteria
- •Expanded Disability Status Scale (EDSS) score between 0 to 6.5, inclusive, at Screening
排除标准
- •For Parts A & B:
- •Benign MS defined as a baseline EDSS of 2.0 with MS diagnosis ≥ 10 years prior to Day
- •Spinal MS without clinical or radiological evidence of brain lesions. Any other combination of clinical and radiological data suggestive of an absence of inflammatory brain lesions.
- •Any major surgery within 4 weeks of study treatment administration and/or any minor surgery within 2 weeks of tracer administration
- •For Part A only:
- •Any significant acute or chronic medical illness
- •For Part B only:
- •Any significant acute or chronic medical illness (other than MS) posing a risk to the participant's safety or negatively affecting the ability to detect CNS PET signal
- •MS relapse within 14 days prior to Day
- •Participants with a MS relapse within 30 days prior to Day 1 must agree to have their second PET scan scheduled on Day 1 or Day 2
- •Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
Part A - Healthy Participants
干预措施: 11C-BMS-986196 (Drug)
Part B - Participants with MS
干预措施: 11C-BMS-986196 (Drug)
结局指标
主要结局
Number of Participants With Clinically Significant Changes in Electrocardiograms.
时间窗: From first visit up to 9 days post
Number of participants with clinically significant changes in electrocardiograms.
Number of Participants With Clinically Significant Changes in Vital Signs.
时间窗: From first visit up to 9 days post
Number of participants with clinically significant changes in vital signs.
Number of Participants With Clinically Significant Changes in Laboratory Values.
时间窗: From first visit up to 9 days post
Number of participants with clinically significant changes in laboratory values.
Number of Participants With Clinically Significant Changes in Phsyical Examinations.
时间窗: From first visit up to 9 days post
Number of participants with clinically significant changes in phsyical examinations.
Number of Participants With Adverse Events Based on Severity.
时间窗: From first visit up to 9 days post
An adverse event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment that does not necessarily have a causal relationship with this treatment.
Number of Participants With Clinically Significant Changes in C-SSRS.
时间窗: Data Not Collected
Number of participants with clinically significant changes in C-SSRS. Columbia-Suicide Severity Rating Scale (C-SSRS). The entire Columbia Suicide Severity Rating Scale (C-SSRS) will be administered, but the investigators will use its' Suicidal Ideation Intensity scale (0-25 score range summed from five items, with higher scores indicating more severe suicidal ideation) as the primary outcome. Data Not Collected
Radiation Dosimetry Calculated From PET-CT Images in Healthy Participants
时间窗: 2 hours
Measurement and assessment of radiation exposure and absorption of ionizing radiation in body tissue. The Organ Level Internal Dose Assessment (OLINDA) 2.0 software package (Hermes Medical Solutions) was used to estimate the organ and whole-body radiation absorbed doses. OLINDA uses Medical Internal Radiation Dose (MIRD) methodology (Stabin, Sparks, and Crowe 2005). The NURBs ICRP-89 adult male (73 kg) model was used to calculate the referent s-factors (Valentin and Streffer 2002). Tissue weighting factors defined in (ICRP Publication 103, 2007) were used to calculate the whole body effective dose (ED). All other MIRD assumptions about the homogeneity of source organ distribution were employed.
Image Acquisition Window After Tracer Administration
时间窗: 90 Mins
Period of time required to collect the imaging data during a scan. Participants received a bolus intravenous administration of up to 370 MBq of 11CBMS- 986196. Immediately following the 11C-BMS-986196 administration, dynamic PET emission data were acquired for 90 minutes in a single bed position focused on the cranium. For PET acquisitions, a low dose CT scan was performed before administration of the radiotracer, to enable correction for attenuation of emitted radiation.
Percentage of Participants With Test Repeatablity Based on SUV.
时间窗: 2 hours
Standardized uptake value (SUV) is Semi-quantitative measurement of tracer uptake in body tissue defined as ratio of radioactivity per unit volume of a region of interest to the radioactivity per unit volume of the whole body. Test-retest repeatability based on standardized uptake value (SUV) of CNS PET images in participants with MS: The test-retest repeatability will be based on a quantitative analysis of cranial PET images and will be evaluated for the Response-Evaluable 3 population. The test-retest repeatability (%), which is defined based upon the absolute value of the difference between test and retest values normalized by their mean: Test-Retest difference = RT-T Test-retest repeatability (%) = 100%-2×\|(RT-T)/(RT+T)\|×100% with T being the calculated value for the parameter measured at Visit 1 (test, T) and RT being the calculated value for the same parameter measured at Visit 2 (retest, RT).
Percentage of Participants With Test Repeatablity Based on VT.
时间窗: 2 Hours
Volume of Distribution (VT) is the ratio of the radioligand concentration in a region of interest to the radioligand concentration in plasma at equilibrium. Test-retest repeatability based on VT of CNS PET images in participants with MS: The test-retest repeatability will be based on a quantitative analysis of cranial PET images and will be evaluated for the Response-Evaluable 3 population. The test-retest repeatability (%), which is defined based upon the absolute value of the difference between test and retest values normalized by their mean: Test-Retest difference = RT-T Test-retest repeatability (%) = 100%-2×\|(RT-T)/(RT+T)\|×100% with T being the calculated value for the parameter measured at Visit 1 (test, T) and RT being the calculated value for the same parameter measured at Visit 2 (retest, RT).
Percentage of Free Brain BTK Relative to Baseline
时间窗: Data Not Collected
Percentage of free brain Burtons Tyrosine Kinase (BTK) relative to baseline
Mean Standardized Uptake Value (SUV) in the Brain
时间窗: On visits 1 (Day 1) and vist 2 (2hrs to 6 days after visit 1 tracer administration)
Standardized uptake value (SUV) is Semi-quantitative measurement of tracer uptake in body tissue defined as ratio of radioactivity per unit volume of a region of interest to the radioactivity per unit volume of the whole body.
Mean Volume of Distribution (VT) in the Brain
时间窗: On visits 1 (Day 1) and vist 2 (2hrs to 6 days after visit 1 tracer administration)
Volume of Distribution (VT) is the ratio of the radioligand concentration in a region of interest to the radioligand concentration in plasma at equilibrium.
次要结局
未报告次要终点