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

May 6, 2026 updated by: 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: A Pilot Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health Clinical Center
        • Contact:
          • NIH Clinical Center Office of Patient Recruitment (OPR)
          • Phone Number: TTY dial 711 800-411-1222
          • Email: ccopr@nih.gov

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Multiple Sclerosis
MS cohort- Up to four study visits. (1) Baseline; (2) Day 0: MRI brain/spinal cord (with gadolinium) followed by an intravenous injection of anti-CD8 minibody (aka"PET/CT tracer"); (3) Day 1: PET/CT scan(4) Optional Visit: PET/CT scan
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).
Experimental: Other Neuroinflammatory diseases with BBB leakage
Up to four study visits: (1) Baseline; (2) Day 0: MRI brain/spinal cord (with gadolinium) followed by an intravenous injection of anti-CD8 minibody (aka "PET/CT tracer"); (3) Day 1: PET/CT scan(4) Optional Visit: PET/CT scan
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).
Experimental: Progressive Multifocal Leukoencephalopathy
PML cohort- Up to seven study visits. (1) Baseline; (2) Day 0: MRI brain (with gadolinium) followed by an intravenous injection of anti-CD8 minibody (aka "PET/CT tracer"); (3) Day 1: PET/CT scan; (4) Study visit 4 (optional): PET/CT scan. (5) Study visit 5 (optional; time-period between study visit 3 and 5 is variable based on radiological criteria): MRI brain (with gadolinium) followed by an intravenous injection of anti-CD8 minibody (aka "PET/CT tracer"); (6) Study visit 6: PET/ CT scan; (7) Study visit 7: PET/CT scan.
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Day 1 Study Visit

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of 89Zr-Dfcrefmirlimab in the participants with CNS disease.
Time Frame: At each study visit
To assess the safety of 89Zr-Dfcrefmirlimab in participants with CNS disease.
At each study visit
For the PML cohort with longitudinal evaluation, effects of immune reconstitution, either spontaneous or facilitated, on 89Zr-Dfcrefmirlimab uptake.
Time Frame: up to 6 months after first PET/CT scan
Comparison of SUV before and after immune reconstitution, either spontaneous or facilitated (for participants with optional follow-up imaging).
up to 6 months after first PET/CT scan
To determine whether 89Zr-Df-crefmirlimab uptake profile in MS and PML is disease-specific.
Time Frame: Comparison of pattern of PET uptake distribution and SUV profiles in MS, PML, and other neuroinflammatory diseases with BBB leakage.
Understand the physiological pattern of 89Zr-Df-crefmirlimab distribution corresponding to normal accumulation of CD8+ T cells.
Comparison of pattern of PET uptake distribution and SUV profiles in MS, PML, and other neuroinflammatory diseases with BBB leakage.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

  • Principal Investigator: Daniel S Reich, M.D., National Institute of Neurological Disorders and Stroke (NINDS)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 19, 2023

Primary Completion (Estimated)

April 1, 2030

Study Completion (Estimated)

December 1, 2030

Study Registration Dates

First Submitted

May 8, 2023

First Submitted That Met QC Criteria

May 8, 2023

First Posted (Actual)

May 9, 2023

Study Record Updates

Last Update Posted (Actual)

May 7, 2026

Last Update Submitted That Met QC Criteria

May 6, 2026

Last Verified

May 5, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 10001519
  • 001519-N

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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