A Study to Evaluate the Safety, Tolerability, Kinetics, Biodistribution and Repeatability of 11C-BMS-986196 After Intravenous (IV) Administration in Healthy Participants and After Repeat IV Administration in Participants With Multiple Sclerosis

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Multiple Sclerosis (MS)

Intervention / Treatment
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* Drug: 11C-BMS-986196


Participation Criteria
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Eligibility Criteria
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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/exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A - Healthy Participants<br> | Drug: 11C-BMS-986196<br>* Specified dose on specified days<br>* Other names: BMS-986196;|
| Experimental: Part B - Participants with MS<br> | Drug: 11C-BMS-986196<br>* Specified dose on specified days<br>* Other names: BMS-986196;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events (AEs) |  | Up to 6 months | 
| Incidence of Treatment-Emergent Adverse Events (TEAEs) |  | Up to 6 months | 
| Incidence of TEAEs by Maximum Severity |  | Up to 6 months | 
| Incidence of Serious TEAEs |  | Up to 6 months | 
| Incidence of TEAEs by System Organ Class |  | Up to 6 months | 
| Incidence of TEAEs by Preferred Term |  | Up to 6 months | 
| Radiation dosimetry calculated from PET-CT images in healthy participants |  | At day 1 | 
| Image acquisition window after administration of 11C-BMS-986196 |  | After 2nd 11C-BMS-986196 administration, Up to 6 days | 
| Test-retest repeatability based on standardized uptake value (SUV) of CNS PET-MRI images in participants with MS |  | After 2nd 11C-BMS-986196 administration, Up to 6 days | 
| Test-retest repeatability based on volume of distribution (VT) of CNS PET-MRI images in participants with MS |  | After 2nd 11C-BMS-986196 administration, Up to 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Calculated SUV in the brain |  | After 2nd 11C-BMS-986196 administration, Up to 6 days | 
| Calculated VT in the brain |  | After 2nd 11C-BMS-986196 administration, Up to 6 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis (MS), Healthy Participants, 11C-BMS-986196, PET tracer