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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-001986-19 | EudraCT Number |
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Business objectives have changed
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A - Healthy Participants | Experimental |
| |
| Part B - Participants with MS | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 11C-BMS-986196 | Drug | Specified dose on specified days |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 electrocardiograms. | 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 vital signs. | 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 laboratory values. | 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 phsyical examinations. | From first visit up to 9 days post |
| 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 |
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Inclusion Criteria:
For Parts A & B:
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:
Exclusion Criteria:
For Parts A & B:
For Part A only:
• Any significant acute or chronic medical illness
For Part B only:
Other protocol-defined inclusion/exclusion criteria apply
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Local Institution - 0001 | Ann Arbor | Michigan | 48109 | United States | ||
| Local Institution - 0002 |
Not provided
| Label | URL |
|---|---|
| BMS Clinical Trial Information | View source |
| BMS Clinical Trial Patient Recruiting | View source |
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10 participants randomized and treated
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A | BMS-986196 Approximately 370MBq, equivalent to up to 20 μg |
| FG001 | Part B | BMS-986196 Approximately 370 MBq, equivalent to up to 20 μg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 30, 2023 | Feb 21, 2025 |
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| Data Not Collected |
| 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. | 2 hours |
| 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. | 90 Mins |
| 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). | 2 hours |
| 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). | 2 Hours |
| Percentage of Free Brain BTK Relative to Baseline | Percentage of free brain Burtons Tyrosine Kinase (BTK) relative to baseline | Data Not Collected |
| 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. | On visits 1 (Day 1) and vist 2 (2hrs to 6 days after visit 1 tracer administration) |
| 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. | On visits 1 (Day 1) and vist 2 (2hrs to 6 days after visit 1 tracer administration) |
| London |
| W12 0HS |
| United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A | BMS-986196 Approximately 370MBq, equivalent to up to 20 μg |
| BG001 | Part B | BMS-986196 Approximately 370 MBq, equivalent to up to 20 μg |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | All Treated Participants | Posted | Count of Participants | Participants | From first visit up to 9 days post |
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| Primary | Number of Participants With Clinically Significant Changes in Electrocardiograms. | Number of participants with clinically significant changes in electrocardiograms. | All Treated Participants | Posted | Count of Participants | Participants | From first visit up to 9 days post |
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| Primary | Number of Participants With Clinically Significant Changes in Vital Signs. | Number of participants with clinically significant changes in vital signs. | All Treated Participants | Posted | Count of Participants | Participants | From first visit up to 9 days post |
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| Primary | Number of Participants With Clinically Significant Changes in Laboratory Values. | Number of participants with clinically significant changes in laboratory values. | All Treated Participants | Posted | Count of Participants | Participants | From first visit up to 9 days post |
|
| |||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Clinically Significant Changes in Phsyical Examinations. | Number of participants with clinically significant changes in phsyical examinations. | All Treated Participants | Posted | Count of Participants | Participants | From first visit up to 9 days post |
|
| |||||||||||||||||||||||||||||||||||||
| 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 | Study terminated before data collection for this endpoint occurred. | Posted | Data Not Collected |
|
| |||||||||||||||||||||||||||||||||||||||
| 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. | All Treated Population | Posted | Mean | Standard Deviation | uSv/MBq | 2 hours |
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| 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. | All Treated Population | Posted | Median | Full Range | Mins | 90 Mins |
|
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| 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). | Response-Evaluable Population with MS, 0 participants in Part A had MS | Posted | Mean | Standard Deviation | percentage | 2 hours |
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| 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). | Response-Evaluable Population 3 with MS, 0 participants in Part A had MS | Posted | Mean | Standard Deviation | percentage | 2 Hours |
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| Primary | Percentage of Free Brain BTK Relative to Baseline | Percentage of free brain Burtons Tyrosine Kinase (BTK) relative to baseline | Study Terminated, data collection for endpoint did not occur. | Posted | Data Not Collected |
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| 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. | Response-Evaluable 2 Population | Posted | Mean | Standard Deviation | g/mL | On visits 1 (Day 1) and vist 2 (2hrs to 6 days after visit 1 tracer administration) |
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| 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. | Response-Evaluable 2 Population | Posted | Mean | Standard Deviation | mL/cm³ | On visits 1 (Day 1) and vist 2 (2hrs to 6 days after visit 1 tracer administration) |
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Adverse Events and Serious Adverse Events: Approximately up to 11 days All-Cause mortality (From randomization to end of study): Approximately up to 11 days
The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A | BMS-986196 Approximately 370MBq, equivalent to up to 20 μg | 0 | 6 | 0 | 6 | 2 | 6 |
| EG001 | Part B | BMS-986196 Approximately 370MBq, equivalent to up to 20 μg | 0 | 4 | 0 | 4 | 3 | 4 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA 27.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 27.0 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 27.0 | Systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | MedDRA 27.0 | Systematic Assessment |
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| Vascular access site bruising | Injury, poisoning and procedural complications | MedDRA 27.0 | Systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA 27.0 | Systematic Assessment |
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Clinically significant abnormalities on ECG, VS, laboratory parameters and PE had to be reported as AE.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bristol-Myers Squibb Study Director | Bristol-Myers Squibb | 1-855-907-3286 | Clinical.Trials@bms.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 12, 2024 | Feb 21, 2025 | SAP_001.pdf |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Severe |
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| Units | Counts |
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| Participants |
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| Participants |
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