Progressive Multifocal LeukoencephalopathyPhase 1NCT05849467
Central Nervous System Uptake of Anti-CD8+ T Cell Minibodies in Multiple Sclerosis and Progressive Multifocal Leukoencephalopathy
A Phase 1 study testing 89 Zr-Df-crefmirlimab in people with Progressive Multifocal Leukoencephalopathy and Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Progressive Multifocal Leukoencephalopathy, Multiple Sclerosis, Other Neuroinflammatory Diseases With BBB Leakage
- What is being tested?
- 89 Zr-Df-crefmirlimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Oct 2023to 1 Dec 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: 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.
Read more
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.
Read the 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
- Progressive Multifocal Leukoencephalopathy, Multiple Sclerosis, Other Neuroinflammatory Diseases With BBB Leakage
- Being tested
- 89 Zr-Df-crefmirlimab
- Keywords
- 89 Zr-Df-crefmirlimab, PET Imaging
- Medical subject headings
- Leukoencephalopathy, Progressive Multifocal, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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).
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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. Receives: Drug: 89 Zr-Df-crefmirlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Comparison of SUV before and after immune reconstitution, either spontaneous or facilitated (for participants with optional follow-up imaging).
Measured: up to 6 months after first PET/CT scan
Safety of 89Zr-Dfcrefmirlimab in the participants with CNS disease.
To assess the safety of 89Zr-Dfcrefmirlimab in participants with CNS disease.
Measured: At each study visit
To determine whether 89Zr-Df-crefmirlimab uptake profile in MS and PML is disease-specific.
Understand the physiological pattern of 89Zr-Df-crefmirlimab distribution corresponding to normal accumulation of CD8+ T cells.
Measured: Comparison of pattern of PET uptake distribution and SUV profiles in MS, PML, and other neuroinflammatory diseases with BBB leakage.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2023
- Study start19 Oct 2023
- Primary completion1 Apr 2030 (estimated)
- Study completion1 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Progressive Multifocal LeukoencephalopathyStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Daniel S Reich, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05849467
- Sponsor's protocol ID
- 10001519
- Other IDs
- 001519-N
- Status last verified
- 3 Jun 2026
- First submitted
- 8 May 2023
- Last updated
- 5 Jun 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Central Nervous System Uptake of Anti-CD8+ T Cell Minibodies in Multiple Sclerosis and Progressive Multifocal Leukoencephalopathy: A Pilot Study
- ClinicalTrials.gov ID
- NCT05849467
- Acronym / sponsor ID
- 10001519
- Conditions
- Progressive Multifocal Leukoencephalopathy, Multiple Sclerosis, Other Neuroinflammatory Diseases With BBB Leakage
- Keywords
- 89 Zr-Df-crefmirlimab, PET Imaging
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 19 Oct 2023 (actual)
- Primary completion
- 1 Apr 2030 (estimated)
- Study completion
- 1 Dec 2030 (estimated)
- First posted
- 9 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Multiple Sclerosis | Experimental | Drug: 89 Zr-Df-crefmirlimabMS 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 |
| Other Neuroinflammatory diseases with BBB leakage | Experimental | Drug: 89 Zr-Df-crefmirlimabUp 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 |
| Progressive Multifocal Leukoencephalopathy | Experimental | Drug: 89 Zr-Df-crefmirlimabPML 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. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 89 Zr-Df-crefmirlimaban 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). | Drug | Multiple Sclerosis, Other Neuroinflammatory diseases with BBB leakage, Progressive Multifocal Leukoencephalopathy |
Primary outcome
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.
3 secondary outcomes
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
Safety of 89Zr-Dfcrefmirlimab in the participants with CNS disease.
Time frame: At each study visit
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Daniel S Reich, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 89 Zr-Df-crefmirlimab in people with Progressive Multifocal Leukoencephalopathy and Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maria I Gaitan, M.D. ((301) 496-1801, maria.gaitan@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2026.