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

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

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.

Study Overview

• Status: Terminated
• Conditions: Multiple Sclerosis (MS)
• Intervention / Treatment: Drug: 11C-BMS-986196

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • Local Institution - 0002
• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Local Institution - 0001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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)

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2021
• Primary Completion (Actual): December 18, 2023
• Study Completion (Actual): December 18, 2023

Study Registration Dates

• First Submitted: September 22, 2021
• First Submitted That Met QC Criteria: September 22, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): April 24, 2025
• Last Update Submitted That Met QC Criteria: April 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Healthy Participants; Multiple Sclerosis (MS); PET tracer; 11C-BMS-986196
• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: IM038-010; 2021-001986-19 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No