NCT05849467 · National Institute of Neurological Disorders and Stroke (NINDS)
Central Nervous System Uptake of Anti-CD8+ T Cell Minibodies in Multiple Sclerosis and Progressive Multifocal Leukoencephalopathy
What this study is about
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.
View original scientific description
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.
Interventions
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).
Primary outcome measures
Infiltration of CD8+ T cells in the CNS of adults with MS and PML via PET-CT scans using a minibody with high affinity for CD8+ T cells.
Time frame: Day 1 Study Visit
To detect and localize infiltration of CD8+ T cells in the CNS of adults with MS and PML via PET-CT scans using a minibody with high affinity for CD8+ T cells.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- In order to be eligible to participate in this study, an individual must meet all of the following criteria: Multiple Sclerosis Inclusion Criteria
- Enrolled in the NINDS Natural History Study for MS (protocol 89-N-0045)
- Able to understand, and willing to sign, a written, informed consent document.
- Willing to comply with all study procedures and available for the duration of the study.
- Male or female, aged \>=18.
- Diagnosis of MS according to the 2017 revision of the McDonald diagnostic criteria48 (in the presence or absence of a clinical relapse). PML Inclusion Criteria
- Enrolled in the NINDS Natural History Study for PML (protocol 13-N-0017)
- Able to understand and willing to sign a written, informed consent document
- Willing to comply with all study procedures and available for the duration of the study.
- Male or female, aged \>=18.
- Diagnosis of definite PML according to 2013 AAN Consensus Criteria49 or PML-IRIS based on clinical, radiological and laboratory evidence. Patients with Known or Suspected Neuroinflammatory Diseases and Evidence of Open BBB Inclusion Criteria -Clinical evaluation suggesting an inflammatory disorder of the central nervous system other than MS or PML. Other confirmed neuroinflammatory disorders may include -MOGAD, NMOSD, Behcet's syndrome, and neurosarcoidosis. Unconfirmed, though suspected cases of neuroinflammation may also be included.
- Recent brain MRI (within 1 month) with gadolinium enhancement indicating open BBB.
- Able to understand and willing to sign a written, informed consent document.
- Willing to comply with all study procedures and available for the duration of the study.
- Male or female, aged \>=18.
Exclusion criteria
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Pregnant or lactating.
- Contraindications for MRI gadolinium contrast administration or 3T MRI.
- History of, or current diagnosis with, concomitant medical or clinical conditions that would adversely affect participation in this study.
- Weighs \> 350 lb. (158 kg; weight limit for the scanner table) or is unable to fit within the MRI or PET imaging gantry.
- Severe claustrophobia unresponsive to oral anxiolytics.
- Has an alkaline phosphatase level greater than 2x ULN (unless known to have non-liver related disorder) OR AST greater than 1.5 x ULN OR ALT greater than 1.5 x ULN.
- Has a total bilirubin \>1.5X ULN, unless known to have elevated bilirubin due to nonliver related disorder or Gilbert s.
- Creatinine clearance \< 60 mL/min as estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
- For females of reproductive potential: inability to use highly effective contraception for at least one month prior to screening and during study participation.
Where
- Bethesda, Maryland
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 5, 2026 · Source of record for eligibility and locations