NCT05849467

Brief 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
15

participants targeted

Target at below P25 for phase_1

Timeline
56mo left

Started Oct 2023

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress36%
Oct 2023Dec 2030

First Submitted

Initial submission to the registry

May 8, 2023

Completed
1 day until next milestone

First Posted

Study publicly available on registry

May 9, 2023

Completed
5 months until next milestone

Study Start

First participant enrolled

October 19, 2023

Completed
6.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2030

Expected
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2030

Last Updated

May 7, 2026

Status Verified

May 5, 2026

Enrollment Period

6.5 years

First QC Date

May 8, 2023

Last Update Submit

May 6, 2026

Conditions

Multiple SclerosisProgressive Multifocal LeukoencephalopathyOther Neuroinflammatory Diseases With BBB Leakage

Keywords

89 Zr-Df-crefmirlimabPET Imaging

Outcome Measures

Primary Outcomes (1)

  • 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.

    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 Outcomes (3)

  • For the PML cohort with longitudinal evaluation, effects of immune reconstitution, either spontaneous or facilitated, on 89Zr-Dfcrefmirlimab uptake.

    up to 6 months after first PET/CT scan

  • Safety of 89Zr-Dfcrefmirlimab in the participants with CNS disease.

    At each study visit

  • To determine whether 89Zr-Df-crefmirlimab uptake profile in MS and PML is disease-specific.

    Comparison of pattern of PET uptake distribution and SUV profiles in MS, PML, and other neuroinflammatory diseases with BBB leakage.

Study Arms (3)

Multiple Sclerosis

EXPERIMENTAL

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

Other Neuroinflammatory diseases with BBB leakage

EXPERIMENTAL

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

Progressive Multifocal Leukoencephalopathy

EXPERIMENTAL

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

Interventions

89 Zr-Df-crefmirlimabDRUG

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).

Multiple SclerosisOther Neuroinflammatory diseases with BBB leakageProgressive Multifocal Leukoencephalopathy

Eligibility Criteria

Age18 Years - 120 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • In order to be eligible to participate in this study, an individual must meet all of the following 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).
  • 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.
  • 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.
  • +2 more criteria

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

MeSH Terms

Conditions

Leukoencephalopathy, Progressive MultifocalMultiple Sclerosis

Condition Hierarchy (Ancestors)

Encephalitis, ViralCentral Nervous System Viral DiseasesCentral Nervous System InfectionsInfectionsInfectious EncephalitisVirus DiseasesPolyomavirus InfectionsDNA Virus InfectionsSlow Virus DiseasesEncephalitisBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesLeukoencephalopathiesDemyelinating DiseasesNeuroinflammatory DiseasesDemyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemAutoimmune DiseasesImmune System Diseases

Study Officials

  • Daniel S Reich, M.D.

    National Institute of Neurological Disorders and Stroke (NINDS)

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria I Gaitan, M.D.

CONTACT

(301) 496-1801maria.gaitan@nih.gov

Daniel S Reich, M.D.

CONTACT

(301) 496-1801reichds@ninds.nih.gov

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 8, 2023

First Posted

May 9, 2023

Study Start

October 19, 2023

Primary Completion (Estimated)

April 1, 2030

Study Completion (Estimated)

December 1, 2030

Last Updated

May 7, 2026

Record last verified: 2026-05-05

Locations

US(1)