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

NCT05064436 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: IM038-0102021-001986-19
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 2

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.

Conditions

Multiple Sclerosis (MS)

Keywords

Multiple Sclerosis (MS); Healthy Participants; 11C-BMS-986196; PET tracer

Outcome Measures

Primary Outcomes (13)

• 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)

Study Arms (2)

Part A - Healthy Participants

EXPERIMENTAL

Drug: 11C-BMS-986196

Part B - Participants with MS

EXPERIMENTAL

Drug: 11C-BMS-986196

Interventions

11C-BMS-986196 DRUG

Specified dose on specified days

Also known as: BMS-986196

Part A - Healthy Participants; Part B - Participants with MS

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (2)

Local Institution - 0001

Ann Arbor, Michigan, 48109, United States

Location

Local Institution - 0002

London, W12 0HS, United Kingdom

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

Clinically significant abnormalities on ECG, VS, laboratory parameters and PE had to be reported as AE.

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

1-855-907-3286

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2021
• First Posted: October 1, 2021
• Study Start: December 10, 2021
• Primary Completion: December 18, 2023
• Study Completion: December 18, 2023
• Last Updated: April 24, 2025
• Results First Posted: April 24, 2025

Record last verified: 2025-04

Locations

US (1); GB (1)