Multiple Sclerosis (MS)
Conditions
Keywords
Multiple Sclerosis (MS), Healthy Participants, 11C-BMS-986196, PET tracer
Brief summary
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.
Interventions
DRUG11C-BMS-986196
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
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
Exclusion criteria
For Parts A & B: * Benign MS defined as a baseline EDSS of 2.0 with MS diagnosis ≥ 10 years prior to Day 1. 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 1. 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events Based on Severity. | 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 Electrocardiograms. | 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. | 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. | 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. | From first visit up to 9 days post | Number of participants with clinically significant changes in phsyical examinations. |
| Number of Participants With Clinically Significant Changes in C-SSRS. | 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 | 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 | 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. | 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. | 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 | Data Not Collected | Percentage of free brain Burtons Tyrosine Kinase (BTK) relative to baseline |
| Mean Standardized Uptake Value (SUV) in the Brain | 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 | 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. |
Countries
United Kingdom, United States
Participant flow
Pre-assignment details
10 participants randomized and treated
Participants by arm
| Arm | Count |
|---|---|
| Part A BMS-986196 Approximately 370MBq, equivalent to up to 20 μg | 6 |
| Part B BMS-986196 Approximately 370 MBq, equivalent to up to 20 μg | 4 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other Reasons | 1 | 0 |
Baseline characteristics
| Characteristic | Part B | Total | Part A |
|---|---|---|---|
| Age, Continuous | 50.8 Years STANDARD_DEVIATION 4 | 41.3 Years STANDARD_DEVIATION 12.3 | 35.0 Years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 9 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 9 Participants | 5 Participants |
| Sex: Female, Male Female | 3 Participants | 6 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 4 |
| other Total, other adverse events | 2 / 6 | 3 / 4 |
| serious Total, serious adverse events | 0 / 6 | 0 / 4 |
Outcome results
Primary
Image Acquisition Window After Tracer Administration
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.
Time frame: 90 Mins
Population: All Treated Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A | Image Acquisition Window After Tracer Administration | 90 Mins |
| Part B | Image Acquisition Window After Tracer Administration | 90 Mins |
Primary
Mean Standardized Uptake Value (SUV) in the Brain
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.
Time frame: On visits 1 (Day 1) and vist 2 (2hrs to 6 days after visit 1 tracer administration)
Population: Response-Evaluable 2 Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Mean Standardized Uptake Value (SUV) in the Brain | Cerebral Cortex-White Matter at visit 2 | 0.606 g/mL | Standard Deviation 0.118 |
| Part A | Mean Standardized Uptake Value (SUV) in the Brain | Cerebellum-Grey Matter at visit 2 | 0.656 g/mL | Standard Deviation 0.135 |
| Part A | Mean Standardized Uptake Value (SUV) in the Brain | Brain-Grey Matter at visit 2 | 0.606 g/mL | Standard Deviation 0.121 |
| Part A | Mean Standardized Uptake Value (SUV) in the Brain | Cerebral Subcortex-Grey Matter at visit 2 | 0.674 g/mL | Standard Deviation 0.122 |
| Part A | Mean Standardized Uptake Value (SUV) in the Brain | Cerebral Cortex-Grey Matter at visit 2 | 0.596 g/mL | Standard Deviation 0.121 |
| Part A | Mean Standardized Uptake Value (SUV) in the Brain | Brain-White Matter at visit 2 | 0.590 g/mL | Standard Deviation 0.108 |
| Part A | Mean Standardized Uptake Value (SUV) in the Brain | Cerebral White Matter-White Matte at visit 2 | 0.550 g/mL | Standard Deviation 0.096 |
| Part A | Mean Standardized Uptake Value (SUV) in the Brain | Cerebellum-White Matter at visit 2 | 0.672 g/mL | Standard Deviation 0.134 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Cerebellum-White Matter at visit 1 | 0.857 g/mL | Standard Deviation 0.099 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Cerebellum-White Matter at visit 2 | 0.780 g/mL | Standard Deviation 0.136 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Cerebral Cortex-Grey Matter at visit 1 | 0.763 g/mL | Standard Deviation 0.101 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Cerebral Cortex-Grey Matter at visit 2 | 0.705 g/mL | Standard Deviation 0.122 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Cerebral Cortex-White Matter at visit 1 | 0.783 g/mL | Standard Deviation 0.101 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Cerebral Cortex-White Matter at visit 2 | 0.725 g/mL | Standard Deviation 0.122 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Cerebral Subcortex-Grey Matter at visit 1 | 0.797 g/mL | Standard Deviation 0.155 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Cerebral Subcortex-Grey Matter at visit 2 | 0.745 g/mL | Standard Deviation 0.159 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Cerebral White Matter-White Matter at visit 1 | 0.723 g/mL | Standard Deviation 0.084 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Brain-Grey Matter at visit 1 | 0.773 g/mL | Standard Deviation 0.101 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Cerebral White Matter-White Matte at visit 2 | 0.658 g/mL | Standard Deviation 0.118 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Brain-Grey Matter at visit 2 | 0.713 g/mL | Standard Deviation 0.122 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Brain-Lesion at visit 1 | 0.677 g/mL | Standard Deviation 0.103 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Brain-Lesion at visit 2 | 0.623 g/mL | Standard Deviation 0.132 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Brain-White Matter at visit 1 | 0.767 g/mL | Standard Deviation 0.098 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Brain-White Matter at visit 2 | 0.705 g/mL | Standard Deviation 0.122 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Cerebellum-Grey Matter at visit 1 | 0.817 g/mL | Standard Deviation 0.099 |
| Part B | Mean Standardized Uptake Value (SUV) in the Brain | Cerebellum-Grey Matter at visit 2 | 0.755 g/mL | Standard Deviation 0.126 |
Primary
Mean Volume of Distribution (VT) in the Brain
Volume of Distribution (VT) is the ratio of the radioligand concentration in a region of interest to the radioligand concentration in plasma at equilibrium.
Time frame: On visits 1 (Day 1) and vist 2 (2hrs to 6 days after visit 1 tracer administration)
Population: Response-Evaluable 2 Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Mean Volume of Distribution (VT) in the Brain | Cerebral Cortex-White Matter at visit 2 | 2.645 mL/cm³ | Standard Deviation 0.39 |
| Part A | Mean Volume of Distribution (VT) in the Brain | Cerebellum-Grey Matter at visit 2 | 2.715 mL/cm³ | Standard Deviation 0.356 |
| Part A | Mean Volume of Distribution (VT) in the Brain | Brain-Grey Matter at visit 2 | 2.498 mL/cm³ | Standard Deviation 0.343 |
| Part A | Mean Volume of Distribution (VT) in the Brain | Cerebral Subcortex-Grey Matter at visit 2 | 2.645 mL/cm³ | Standard Deviation 0.404 |
| Part A | Mean Volume of Distribution (VT) in the Brain | Cerebral Cortex-Grey Matter at visit 2 | 2.453 mL/cm³ | Standard Deviation 0.338 |
| Part A | Mean Volume of Distribution (VT) in the Brain | Brain-White Matter at visit 2 | 2.645 mL/cm³ | Standard Deviation 0.417 |
| Part A | Mean Volume of Distribution (VT) in the Brain | Cerebral White Matter-White Matte at visit 2 | 2.675 mL/cm³ | Standard Deviation 0.496 |
| Part A | Mean Volume of Distribution (VT) in the Brain | Cerebellum-White Matter at visit 2 | 2.953 mL/cm³ | Standard Deviation 0.35 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Cerebellum-White Matter at visit 1 | 2.883 mL/cm³ | Standard Deviation 0.427 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Cerebellum-White Matter at visit 2 | 2.903 mL/cm³ | Standard Deviation 0.822 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Cerebral Cortex-Grey Matter at visit 1 | 2.340 mL/cm³ | Standard Deviation 0.198 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Cerebral Cortex-Grey Matter at visit 2 | 2.470 mL/cm³ | Standard Deviation 0.578 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Cerebral Cortex-White Matter at visit 1 | 2.540 mL/cm³ | Standard Deviation 0.294 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Cerebral Cortex-White Matter at visit 2 | 2.680 mL/cm³ | Standard Deviation 0.66 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Cerebral Subcortex-Grey Matter at visit 1 | 2.445 mL/cm³ | Standard Deviation 0.315 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Cerebral Subcortex-Grey Matter at visit 2 | 2.710 mL/cm³ | Standard Deviation 0.815 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Cerebral White Matter-White Matter at visit 1 | 2.790 mL/cm³ | Standard Deviation 0.613 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Brain-Grey Matter at visit 1 | 2.378 mL/cm³ | Standard Deviation 0.213 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Cerebral White Matter-White Matte at visit 2 | 2.665 mL/cm³ | Standard Deviation 0.712 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Brain-Grey Matter at visit 2 | 2.505 mL/cm³ | Standard Deviation 0.604 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Brain-Lesion at visit 1 | 2.805 mL/cm³ | Standard Deviation 0.68 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Brain-Lesion at visit 2 | 3.095 mL/cm³ | Standard Deviation 1.407 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Brain-White Matter at visit 1 | 2.608 mL/cm³ | Standard Deviation 0.374 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Brain-White Matter at visit 2 | 2.660 mL/cm³ | Standard Deviation 0.677 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Cerebellum-Grey Matter at visit 1 | 2.535 mL/cm³ | Standard Deviation 0.219 |
| Part B | Mean Volume of Distribution (VT) in the Brain | Cerebellum-Grey Matter at visit 2 | 2.638 mL/cm³ | Standard Deviation 0.639 |
Primary
Number of Participants With Adverse Events Based on Severity.
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.
Time frame: From first visit up to 9 days post
Population: All Treated Participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Number of Participants With Adverse Events Based on Severity. | Mild | 1 Participants |
| Part A | Number of Participants With Adverse Events Based on Severity. | Moderate | 1 Participants |
| Part A | Number of Participants With Adverse Events Based on Severity. | Severe | 0 Participants |
| Part B | Number of Participants With Adverse Events Based on Severity. | Mild | 1 Participants |
| Part B | Number of Participants With Adverse Events Based on Severity. | Moderate | 2 Participants |
| Part B | Number of Participants With Adverse Events Based on Severity. | Severe | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in C-SSRS.
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
Time frame: Data Not Collected
Population: Study terminated before data collection for this endpoint occurred.
Primary
Number of Participants With Clinically Significant Changes in Electrocardiograms.
Number of participants with clinically significant changes in electrocardiograms.
Time frame: From first visit up to 9 days post
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A | Number of Participants With Clinically Significant Changes in Electrocardiograms. | 0 Participants |
| Part B | Number of Participants With Clinically Significant Changes in Electrocardiograms. | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Laboratory Values.
Number of participants with clinically significant changes in laboratory values.
Time frame: From first visit up to 9 days post
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A | Number of Participants With Clinically Significant Changes in Laboratory Values. | 0 Participants |
| Part B | Number of Participants With Clinically Significant Changes in Laboratory Values. | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Phsyical Examinations.
Number of participants with clinically significant changes in phsyical examinations.
Time frame: From first visit up to 9 days post
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A | Number of Participants With Clinically Significant Changes in Phsyical Examinations. | 2 Participants |
| Part B | Number of Participants With Clinically Significant Changes in Phsyical Examinations. | 3 Participants |
Primary
Number of Participants With Clinically Significant Changes in Vital Signs.
Number of participants with clinically significant changes in vital signs.
Time frame: From first visit up to 9 days post
Population: All Treated Participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A | Number of Participants With Clinically Significant Changes in Vital Signs. | 0 Participants |
| Part B | Number of Participants With Clinically Significant Changes in Vital Signs. | 0 Participants |
Primary
Percentage of Free Brain BTK Relative to Baseline
Percentage of free brain Burtons Tyrosine Kinase (BTK) relative to baseline
Time frame: Data Not Collected
Population: Study Terminated, data collection for endpoint did not occur.
Primary
Percentage of Participants With Test Repeatablity Based on SUV.
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).
Time frame: 2 hours
Population: Response-Evaluable Population with MS, 0 participants in Part A had MS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B | Percentage of Participants With Test Repeatablity Based on SUV. | Brain-Grey Matter | 96.163 percentage | Standard Deviation 3.621 |
| Part B | Percentage of Participants With Test Repeatablity Based on SUV. | Brain-Lesion | 95.930 percentage | Standard Deviation 3.427 |
| Part B | Percentage of Participants With Test Repeatablity Based on SUV. | Brain-White Matter | 96.128 percentage | Standard Deviation 3.67 |
| Part B | Percentage of Participants With Test Repeatablity Based on SUV. | Cerebellum-Grey Matter | 95.114 percentage | Standard Deviation 3.557 |
| Part B | Percentage of Participants With Test Repeatablity Based on SUV. | Cerebellum-White Matter | 93.541 percentage | Standard Deviation 6.164 |
| Part B | Percentage of Participants With Test Repeatablity Based on SUV. | Cerebral Cortex-Grey Matter | 96.601 percentage | Standard Deviation 3.675 |
| Part B | Percentage of Participants With Test Repeatablity Based on SUV. | Cerebral Cortex-White Matter | 96.697 percentage | Standard Deviation 3.571 |
| Part B | Percentage of Participants With Test Repeatablity Based on SUV. | Cerebral Subcortex-Grey Matter | 95.833 percentage | Standard Deviation 2.957 |
| Part B | Percentage of Participants With Test Repeatablity Based on SUV. | Cerebral White Matter-White Matter | 95.912 percentage | Standard Deviation 3.893 |
Primary
Percentage of Participants With Test Repeatablity Based on VT.
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).
Time frame: 2 Hours
Population: Response-Evaluable Population 3 with MS, 0 participants in Part A had MS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part B | Percentage of Participants With Test Repeatablity Based on VT. | Brain-Grey Matter | 88.339 percentage | Standard Deviation 10.476 |
| Part B | Percentage of Participants With Test Repeatablity Based on VT. | Brain-Lesion | 73.396 percentage | Standard Deviation 6.751 |
| Part B | Percentage of Participants With Test Repeatablity Based on VT. | Brain-White Matter | 85.514 percentage | Standard Deviation 8.202 |
| Part B | Percentage of Participants With Test Repeatablity Based on VT. | Cerebellum-Grey Matter | 88.486 percentage | Standard Deviation 9.884 |
| Part B | Percentage of Participants With Test Repeatablity Based on VT. | Cerebellum-White Matter | 85.167 percentage | Standard Deviation 11.593 |
| Part B | Percentage of Participants With Test Repeatablity Based on VT. | Cerebral Cortex-Grey Matter | 88.114 percentage | Standard Deviation 9.931 |
| Part B | Percentage of Participants With Test Repeatablity Based on VT. | Cerebral Cortex-White Matter | 87.262 percentage | Standard Deviation 9.439 |
| Part B | Percentage of Participants With Test Repeatablity Based on VT. | Cerebral Subcortex-Grey Matter | 83.233 percentage | Standard Deviation 9.408 |
| Part B | Percentage of Participants With Test Repeatablity Based on VT. | Cerebral White Matter-White Matter | 79.804 percentage | Standard Deviation 8.192 |
Primary
Radiation Dosimetry Calculated From PET-CT Images in Healthy Participants
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.
Time frame: 2 hours
Population: All Treated Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A | Radiation Dosimetry Calculated From PET-CT Images in Healthy Participants | 4.36 uSv/MBq | Standard Deviation 0.57 |