NCT05849467

Central Nervous System Uptake of Anti-CD8+ T Cell Minibodies in Multiple Sclerosis and Progressive Multifocal Leukoencephalopathy

Central Nervous System Uptake of Anti-CD8+ T Cell Minibodies in Multiple Sclerosis and Progressive Multifocal Leukoencephalopathy: A Pilot Study

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Sponsor: National Institute of Neurological Disorders and Stroke (NINDS) · NIH
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

Summary

Background: Multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML) are disorders that affect the central nervous system (CNS). The CNS includes the brain, spinal cord, and optic nerves. Both diseases can cause muscle weakness and impair vision, speech, and coordination. Researchers are working to better understand how MS and PML affect the CNS. Objective: To test whether an experimental radioactive tracer (minibody) can help positron emission tomography (PET) scans detect certain immune cells in the CNS of people with MS and PML. Eligibility: People aged 18 years and older with MS, other neuroinflammatory diseases with BBB leakage, or PML. Design: Participants will come to the clinic for at least 3 visits over 4 to 6 weeks. Participants will undergo testing. They will have a physical and neurological exam. They will have blood tests and tests of their heart function. They will have a magnetic resonance imaging (MRI) scan of the brain. They may have a spinal tap: Their lower back will be numbed, and a needle will be inserted between the bones of the spine to withdraw fluid from around the spinal cord. Minibody is given through a tube with a needle placed in a vein in the arm. This takes 5 to 10 minutes. Participants will have heart function tests before and after receiving the minibody. Participants may have a PET scan on the day of the Minibody and will return the next day for another PET scan. They will lie on a table that moves through a doughnut-shaped machine. This scan will take about 1 hour. Participants with PML may opt to repeat the minibody infusion and the PET scan within 6 months.

Detailed description

Study Description: This study will obtain pilot data for noninvasive positron emission tomography (PET) imaging of CD8 plus T lymphocytes in two inflammatory central nervous system (CNS) demyelinating diseases, multiple sclerosis (MS) and progressive multifocal leukoencephalopathy (PML), and other neuroinflammatory diseases by characterizing CNS uptake of anti-CD8 plus T cell antibody fragment (aka minibody ) (89Zr-Df-crefmirlimab), an investigational, intravenous PET tracer. Objectives: Primary Objective: To detect and localize infiltration of CD8 plus T cells in the CNS of adults with MS and PML via PET-CT (computed tomography) scans using a minibody with high affinity for CD8 plus T cells. Secondary Objectives: (1) To characterize safety and tolerability of 89Zr-Df-crefmirlimab in the participant population. (2) For the PML cohort with longitudinal evaluation, to determine the effects of immune reconstitution, either spontaneous or facilitated, on 89Zr-Dfcrefmirlimab uptake. (3) To determine whether 89Zr-Df-crefmirlimab uptake profile is disease specific for MS and PML. Endpoints: Primary Endpoints: Standardized uptake values (SUV) in different tissue types (lesions, white matter, gray matter, meninges, choroid plexus, as determined from coregistered MRI) in each cohort (MS or PML) by region-of-interest (ROI) analysis. Secondary Endpoints: (1) Frequency and nature of adverse events; (2) For the PML cohort with longitudinal evaluation, changes in SUV over time. (3) Compare patterns of uptake distribution across PML, MS, and other neuroinflammatory diseases with BBB leakage.

Conditions

• Multiple Sclerosis
• Progressive Multifocal Leukoencephalopathy

Interventions

Type	Name	Description
DRUG	89 Zr-Df-crefmirlimab	an 80 kDa minibody (Mb) with high affinity to CD8 glycoprotein (binding EC50 = 0.4 nM) that is conjugated with deferoxamine (Df) and radiolabeled with the positron emitting radionuclide, Zr-89 (T1/2 78.4 hours).

Timeline

• Start date: 2023-10-19
• Primary completion: 2026-06-30
• Completion: 2026-06-30
• First posted: 2023-05-09
• Last updated: 2026-04-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study