Ignite Creation Date:
2025-12-25 @ 12:31 AM
Ignite Modification Date:
2026-02-21 @ 5:56 AM
Study NCT ID:
NCT05849467
Status:
RECRUITING
Last Update Posted:
2025-09-15
First Post:
2023-05-08
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Central Nervous System Uptake of Anti-CD8+ T Cell Minibodies in Multiple Sclerosis and Progressive Multifocal Leukoencephalopathy
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D009103', 'term': 'Multiple Sclerosis'}, {'id': 'D007968', 'term': 'Leukoencephalopathy, Progressive Multifocal'}], 'ancestors': [{'id': 'D020278', 'term': 'Demyelinating Autoimmune Diseases, CNS'}, {'id': 'D020274', 'term': 'Autoimmune Diseases of the Nervous System'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D003711', 'term': 'Demyelinating Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D018792', 'term': 'Encephalitis, Viral'}, {'id': 'D020805', 'term': 'Central Nervous System Viral Diseases'}, {'id': 'D002494', 'term': 'Central Nervous System Infections'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D000069544', 'term': 'Infectious Encephalitis'}, {'id': 'D014777', 'term': 'Virus Diseases'}, {'id': 'D027601', 'term': 'Polyomavirus Infections'}, {'id': 'D004266', 'term': 'DNA Virus Infections'}, {'id': 'D012897', 'term': 'Slow Virus Diseases'}, {'id': 'D004660', 'term': 'Encephalitis'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D056784', 'term': 'Leukoencephalopathies'}, {'id': 'D000090862', 'term': 'Neuroinflammatory Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 15}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-10-19', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09-11', 'completionDateStruct': {'date': '2026-06-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-09-12', 'studyFirstSubmitDate': '2023-05-08', 'studyFirstSubmitQcDate': '2023-05-08', 'lastUpdatePostDateStruct': {'date': '2025-09-15', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2023-05-09', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2026-06-30', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'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.', 'timeFrame': 'Day 1 Study Visit', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'For the PML cohort with longitudinal evaluation, effects of immune reconstitution, either spontaneous or facilitated, on 89Zr-Dfcrefmirlimab uptake.', 'timeFrame': 'up to 6 months after first PET/CT scan', 'description': 'Comparison of SUV before and after immune reconstitution, either spontaneous or facilitated (for participants with optional follow-up imaging).'}, {'measure': 'Safety of 89Zr-Dfcrefmirlimab in the participants with CNS disease.', 'timeFrame': 'At each study visit', 'description': 'To assess the safety of 89Zr-Dfcrefmirlimab in participants with CNS disease.'}, {'measure': 'To determine whether 89Zr-Df-crefmirlimab uptake profile in MS and PML is disease-specific.', 'timeFrame': 'Comparison of pattern of PET uptake distribution and SUV profiles in MS, PML, and other neuroinflammatory diseases with BBB leakage.', 'description': 'Understand the physiological pattern of 89Zr-Df-crefmirlimab distribution corresponding to normal accumulation of CD8+ T cells.'}]}, 'oversightModule': {'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['89 Zr-Df-crefmirlimab', 'PET Imaging'], 'conditions': ['Multiple Sclerosis', 'Progressive Multifocal Leukoencephalopathy']}, 'referencesModule': {'seeAlsoLinks': [{'url': 'https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_001519-N.html', 'label': 'NIH Clinical Center Detailed Web Page'}]}, 'descriptionModule': {'briefSummary': 'Background:\n\nMultiple 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.\n\nObjective: 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.\n\nEligibility:\n\nPeople aged 18 years and older with MS, other neuroinflammatory diseases with BBB leakage, or PML.\n\nDesign:\n\nParticipants will come to the clinic for at least 3 visits over 4 to 6 weeks.\n\nParticipants 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.\n\nMinibody 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.\n\nParticipants 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.\n\nParticipants with PML may opt to repeat the minibody infusion and the PET scan within 6 months.', 'detailedDescription': 'Study Description:\n\nThis 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.\n\nObjectives:\n\nPrimary 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.\n\nSecondary 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.\n\nEndpoints:\n\nPrimary 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.\n\nSecondary 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '120 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': '* INCLUSION CRITERIA:\n\nIn order to be eligible to participate in this study, an individual must meet all of the following criteria:\n\nMultiple Sclerosis Inclusion Criteria\n\n* Enrolled in the NINDS Natural History Study for MS (protocol 89-N-0045)\n* Able to understand, and willing to sign, a written, informed consent document.\n* Willing to comply with all study procedures and available for the duration of the study.\n* Male or female, aged \\>=18.\n* Diagnosis of MS according to the 2017 revision of the McDonald diagnostic criteria48 (in the presence or absence of a clinical relapse).\n\nPML Inclusion Criteria\n\n* Enrolled in the NINDS Natural History Study for PML (protocol 13-N-0017)\n* Able to understand and willing to sign a written, informed consent document\n* Willing to comply with all study procedures and available for the duration of the study.\n* Male or female, aged \\>=18.\n* Diagnosis of definite PML according to 2013 AAN Consensus Criteria49 or PML-IRIS based on clinical, radiological and laboratory evidence.\n\nPatients with Known or Suspected Neuroinflammatory Diseases and Evidence of Open BBB Inclusion Criteria\n\n* Clinical evaluation suggesting an inflammatory disorder of the central nervous system other than MS or PML.\n* Recent brain MRI (within 1 month) with gadolinium enhancement indicating open BBB.\n* Able to understand and willing to sign a written, informed consent document.\n* Willing to comply with all study procedures and available for the duration of the study.\n* Male or female, aged \\>=18.\n\nEXCLUSION CRITERIA:\n\nAn individual who meets any of the following criteria will be excluded from participation in this study:\n\n* Pregnant or lactating.\n* Contraindications for MRI gadolinium contrast administration or 3T MRI.\n* History of, or current diagnosis with, concomitant medical or clinical conditions that would adversely affect participation in this study.\n* Weighs \\> 350 lb (158 kg; weight limit for the scanner table) or is unable to fit within the MRI or PET imaging gantry.\n* Severe claustrophobia unresponsive to oral anxiolytics.\n* 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.\n* Has a total bilirubin \\>1.5X ULN, unless known to have elevated bilirubin due to nonliver related disorder or Gilbert s.\n* Creatinine clearance \\< 60 mL/min as estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)\n* For females of reproductive potential: inability to use highly effective contraception for at least one month prior to screening and during study participation.'}, 'identificationModule': {'nctId': 'NCT05849467', 'briefTitle': 'Central Nervous System Uptake of Anti-CD8+ T Cell Minibodies in Multiple Sclerosis and Progressive Multifocal Leukoencephalopathy', 'organization': {'class': 'NIH', 'fullName': 'National Institutes of Health Clinical Center (CC)'}, 'officialTitle': 'Central Nervous System Uptake of Anti-CD8+ T Cell Minibodies in Multiple Sclerosis and Progressive Multifocal Leukoencephalopathy: A Pilot Study', 'orgStudyIdInfo': {'id': '10001519'}, 'secondaryIdInfos': [{'id': '001519-N'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Multiple Sclerosis', 'description': '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', 'interventionNames': ['Drug: 89 Zr-Df-crefmirlimab']}, {'type': 'EXPERIMENTAL', 'label': 'Other Neuroinflammatory diseases with BBB leakage', 'description': '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', 'interventionNames': ['Drug: 89 Zr-Df-crefmirlimab']}, {'type': 'EXPERIMENTAL', 'label': 'Progressive Multifocal Leukoencephalopathy', 'description': 'PML cohort- Up to five 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; time-period between study visit 3 and 4 is variable): MRI brain (with gadolinium) followed by an intravenous injection of anti-CD8 minibody (aka "PET/CT tracer") following clinical, radiological and/or laboratory-defined immune reconstitution (spontaneous or facilitated); (5) Study visit 5: PET/ CT scan', 'interventionNames': ['Drug: 89 Zr-Df-crefmirlimab']}], 'interventions': [{'name': '89 Zr-Df-crefmirlimab', 'type': 'DRUG', 'description': 'an 80 kDa minibody (Mb) with high\n\naffinity to CD8 glycoprotein (binding EC50 = 0.4 nM) that is conjugated with deferoxamine (Df)\n\nand radiolabeled with the positron emitting radionuclide, Zr-89 (T1/2 78.4 hours).', 'armGroupLabels': ['Multiple Sclerosis', 'Other Neuroinflammatory diseases with BBB leakage', 'Progressive Multifocal Leukoencephalopathy']}]}, 'contactsLocationsModule': {'locations': [{'zip': '20892', 'city': 'Bethesda', 'state': 'Maryland', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'NIH Clinical Center Office of Patient Recruitment (OPR)', 'role': 'CONTACT', 'email': 'ccopr@nih.gov', 'phone': '800-411-1222', 'phoneExt': 'TTY dial 711'}], 'facility': 'National Institutes of Health Clinical Center', 'geoPoint': {'lat': 38.98067, 'lon': -77.10026}}], 'centralContacts': [{'name': 'Maria I Gaitan, M.D.', 'role': 'CONTACT', 'email': 'maria.gaitan@nih.gov', 'phone': '(301) 496-1801'}, {'name': 'Daniel S Reich, M.D.', 'role': 'CONTACT', 'email': 'reichds@ninds.nih.gov', 'phone': '(301) 496-1801'}], 'overallOfficials': [{'name': 'Daniel S Reich, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'National Institute of Neurological Disorders and Stroke (NINDS)'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Institute of Neurological Disorders and Stroke (NINDS)', 'class': 'NIH'}, 'responsibleParty': {'type': 'SPONSOR'}}}}