DementiaPhase 2NCT06489548
Assessment of Foralumab Safety and Modulation of Microglial Activation in Alzheimer's Disease
A Phase 2 study testing Foralumab TZLS-401 50 µg and Foralumab TZLS-401 100 µg in people with Dementia and Alzheimers Disease, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
This phase 2a study will research the safety and tolerability of Foralumab, a human anti-CD3 antibody. An antibody is a molecule secreted by the immune system. These molecules are created to identify a specific pathogen. Read more about this study
- Who is it for?
- Ages 60 to 85 years
- Conditions the study is for
- Dementia, Alzheimers Disease, Mild Cognitive Impairment Due to Alzheimer's Disease
- What is being tested?
- Foralumab TZLS-401 50 µg and Foralumab TZLS-401 100 µg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Sep 2025to Dec 2026
- Phase
- Phase 2
- 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 60 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The Sponsor will rely on NIA-AA Alzheimer's Disease Diagnostic Guidelines for Early Symptomatic Alzheimer's Disease (AD) with a 20-30 MMSE score, Clinical Dementia Rating (CDR) global score of 0.5 or 1, and impaired memory performance below an education adjusted cut-off score on the Logical Memory II subscale delayed paragraph recall (LM-IIa) of the Wechsler Memory Scale- Revised (WMS-R) (127) (≥16 years: ≤8; 8-15 years: ≤4; 0-7 years: ≤2).
- Age between 60 and 85 years (inclusive).
- Good general health with no disease likely to interfere with the study assessments.
- On a stable medication regimen for eight weeks prior to the study and is anticipated to remain stable during the study.
- Subject is not pregnant, lactating, or of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile). If a woman is of childbearing potential, her partner must use barrier contraception throughout the study.
- Amyloid-positive PET scan (performed only if the subject meets all other inclusion criteria). An amyloid-positive PET scan is classified by an SUVR composite score cutoff of 1.18 units. Prior evidence of amyloid positivity by PET or CSF will also be accepted for eligibility.
- Ability to understand and provide informed consent.
- Has availability of a study partner who has regular contact with the participant and knows him/her well.
Who cannot join
- Any significant neurologic disease including Parkinson's disease, stroke, multiinfarct dementia, frontotemporal dementia, Lewy body dementia, normal pressure hydrocephalus, brain tumor, brain hemorrhage with persistent neurologic deficits, progressive supra-nuclear palsy, seizure disorder, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.
- Clinically significant or unstable medical conditions, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic diseases.
- History of autoimmune disease.
- Current treatment with immunomodulatory or immunosuppressive drugs or corticosteroid administration by any route of administration (including nasal corticosteroids) within the past month.
- Major depressive disorder (within the past 1 year), or a history of bipolar disorder, or a history of schizophrenia.
- History of alcohol or substance abuse or dependence within the past two years.
Show all 14Show fewer
- History of malignancy within the past 3 years.
- Clinically significant abnormalities in screening laboratories (defined as greater than mild on the FDA's vaccine toxicity grading scale).
- Participation in another clinical trial of an investigational drug concurrently or within the past 30 days.
- Low affinity TSPO binders (for PET ligand [18F]PBR06) determined by having a Thr/Thr polymorphism in the TSPO gene at screening.
- Sensitivity to florbetapir F18.
- Active COVID-19 disease.
- Amyloid-negative PET scan.
- COVID-19 vaccine within the past ten days or any other vaccine within the past seven days (at dosing)
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
Center for Alzheimer Research and Treatment, Brigham and Women's Hospital
Boston, Massachusetts, 02115
Gad Marshall, MD, 617-525-6754, foralumab@mgb.org
About this study
Official title: Assessment of Foralumab Safety and Modulation of Microglial Activation Evaluated by PET Imaging in Patients With Early Symptomatic Alzheimer's Disease
This phase 2a study will research the safety and tolerability of Foralumab, a human anti-CD3 antibody. An antibody is a molecule secreted by the immune system. These molecules are created to identify a specific pathogen. Previous data on experimental mice has suggested that Foralumab increases the immune system activity in the brain to reduce the inflammation of microglia, the brain's main immune cells. This combination of increased immune reactivity and less microglia inflammation may improve the immune response throughout the brain. Alzheimer's disease and other forms of dementia are characteristically known for the build-up of certain proteins in the brain. This trial will evaluate whether nasal Foralumab can improve cognition in participants with mild cognitive impairment due to early Alzheimer's or dementia.
The trial will ask participants to administer Foralumab nasally three times a week for eight weeks. The administration will occur intermittently, with breaks between each dosing cycle. Participants will also receive brain scans (Amyloid PET and MRI), undergo cognitive testing, blood draws, and physical, neurological, and nasal exams. Volunteers are expected to remain in the trial for six months.
Read the detailed description
Preliminary data has shown that Foralumab, a human anti-CD3 antibody, may improve cognition in APP/PS1and 3xTg mouse models of AD. Nasal Foralumab has been given to healthy volunteers with progressive multiple sclerosis (MS). When given nasally for five consecutive days, doeses up to 250 µg are well-tolerated.
This is a randomized, double-blind, placebo-controlled study assessing two dose levels of nasal foralumab (50 µg/dosing day and 100 µg/dosing day) or placebo, given in three-week "treatment cycles". A treatment cycle is defined as Investigational Product (IP) dosing on Monday, Wednesday, and Friday for two consecutive weeks, followed by a one-week pause in dosing or a "rest week." All treatment cycles follow the identical dosing regimen. Randomization will be 3:1 Active to Placebo.
Two cohorts of eight (8) subjects each will be enrolled in this study, and enrollment in these cohorts will be staggered. Both cohorts, Cohort A and Cohort B, will consist of six (6) subjects who will complete three months (4 cycles) of active treatment and two (2) subjects who receive Placebo treatment. Enrollment into Cohort B may begin once all subjects in Cohort A complete 2 cycles of treatment.
Subjects will be screened and enrolled at the Center for Alzheimer Research and Treatment (CART). Initial treatment visits will occur in the Center for Clinical Investigation (CCI) with follow-up visits occurring in CART. Both centers are in the Building for Transformative Medicine, Brigham and Women's Hospital (BWH) at 60 Fenwood Road, Boston, MA 02115.
Subjects will undergo screening procedures, including laboratory studies (hematology, clinical chemistry, CRP, EBV serology, HIV testing, Hepatitis B and Hepatitis C), vital signs, cognitive testing, and a complete physical exam by the physician investigator or a mid-level practitioner, and a detailed neurologic examination performed by a neurologist. Each subject must have normal laboratory tests, or results must be in a clinically acceptable range in the opinion of the Investigator. An additional screening visit will consist of an amyloid PET scan (if subjects do not already have those results prior to screening). Prior to each treatment cycle and at the end of treatment, an ENT physician will conduct a nasal exam and safety blood labs will be collected. At baseline and end of treatment, each subject will have blood samples collected for immunological study and undergo an MRI and a microglial PET scan. Blood samples for immunologic studies will be collected at baseline and after 3 months of treatment. A lumbar puncture will be performed at the screening visit and after 3 months of treatment to assess for changes in amyloid and tau.
- Being tested
- Foralumab TZLS-401 50 µg, Foralumab TZLS-401 100 µg
- Keywords
- Alzheimers, Dementia, Mild Cognitive Impairment
- Medical subject headings
- Dementia, Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Foralumab TZLS-401 50 µgDrug
Foralumab is a nasal anti-CD3 antibody. It will be administered in doses of 50 µg vs. placebo.
Foralumab TZLS-401 100 µgDrug
Foralumab is a nasal anti-CD3 antibody. It will be administered in doses of 100 µg vs. placebo.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: This cohort of subjects will receive 100µg/dosing day vs. placebo throughout the study. | Active comparator | This group will receive a nasal spray three times a week for two weeks, followed by a one-week rest. That cycle will occur three more times for a total of three months of drug intervention. Receives: Drug: Foralumab TZLS-401 100 µg |
| Arm B: This cohort of subjects will receive 50µg/dosing day vs. placebo throughout the study. | Active comparator | This group will receive a nasal spray three times a week for two weeks, followed by a one-week rest. That cycle will occur three more times for a total of three months of drug intervention. Receives: Drug: Foralumab TZLS-401 50 µg |
What is being measured
The primary outcome is the main question the study is designed to answer.
The number of adverse events in drug versus placebo groups.
Establish the safety and tolerability of nasal foralumab dosing in subjects as a percentage of drug and placebo groups who experience adverse events.
Measured: From baseline to the end of study, up to 20 weeks.
Assessment of microglial function via PET scan using the ligand [18F]PBR06
The ligand [18F]PBR06 provides a quantification of microglial activation during a PET scan. The investigatorshope to use this tracer at the start and end of the study to examine how the use of Foralumab may affect microglial function.
Measured: From baseline to end of study, up to 20 weeks.
Measure the effect of foralumab on the ratio of CD4/CD8 memory/naïve T cells biomarkers in blood
Measured: From baseline to the end of treatment, up to 12 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jul 2024
- Study start16 Sep 2025
- Primary completionJun 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for DementiaStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Tiziana Life Sciences LTD
- Responsible party
- Principal investigator, Gad A. Marshall, MD, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06489548
- Sponsor's protocol ID
- 2023P003329
- Other IDs
- TILS-024
- Status last verified
- Feb 2026
- First submitted
- 28 May 2024
- Last updated
- 12 Feb 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zhou R, Ji B, Kong Y, Qin L, Ren W, Guan Y, Ni R. PET Imaging of Neuroinflammation in Alzheimer's Disease. Front Immunol. 2021 Sep 16;12:739130. doi: 10.3389/fimmu.2021.739130. eCollection 2021.
PubMed 34603323Wu HY, Quintana FJ, Weiner HL. Nasal anti-CD3 antibody ameliorates lupus by inducing an IL-10-secreting CD4+ CD25- LAP+ regulatory T cell and is associated with down-regulation of IL-17+ CD4+ ICOS+ CXCR5+ follicular helper T cells. J Immunol. 2008 Nov 1;181(9):6038-50. doi: 10.4049/jimmunol.181.9.6038.
PubMed 18941193Toly-Ndour C, Lui G, Nunes MM, Bruley-Rosset M, Aucouturier P, Dorothee G. MHC-independent genetic factors control the magnitude of CD4+ T cell responses to amyloid-beta peptide in mice through regulatory T cell-mediated inhibition. J Immunol. 2011 Nov 1;187(9):4492-500. doi: 10.4049/jimmunol.1003953. Epub 2011 Sep 26.
PubMed 21949026Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008 May 30;133(5):775-87. doi: 10.1016/j.cell.2008.05.009.
PubMed 18510923Ogura M, Deng S, Preston-Hurlburt P, Ogura H, Shailubhai K, Kuhn C, Weiner HL, Herold KC. Oral treatment with foralumab, a fully human anti-CD3 monoclonal antibody, prevents skin xenograft rejection in humanized mice. Clin Immunol. 2017 Oct;183:240-246. doi: 10.1016/j.clim.2017.07.005. Epub 2017 Jul 21.
PubMed 28739191Moreira TG, Matos KTF, De Paula GS, Santana TMM, Da Mata RG, Pansera FC, Cortina AS, Spinola MG, Baecher-Allan CM, Keppeke GD, Jacob J, Palejwala V, Chen K, Izzy S, Healey BC, Rezende RM, Dedivitis RA, Shailubhai K, Weiner HL. Nasal Administration of Anti-CD3 Monoclonal Antibody (Foralumab) Reduces Lung Inflammation and Blood Inflammatory Biomarkers in Mild to Moderate COVID-19 Patients: A Pilot Study. Front Immunol. 2021 Aug 12;12:709861. doi: 10.3389/fimmu.2021.709861. eCollection 2021.
PubMed 34475873Mayo L, Cunha AP, Madi A, Beynon V, Yang Z, Alvarez JI, Prat A, Sobel RA, Kobzik L, Lassmann H, Quintana FJ, Weiner HL. IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation. Brain. 2016 Jul;139(Pt 7):1939-57. doi: 10.1093/brain/aww113. Epub 2016 May 31.
PubMed 27246324Kuhn C, Weiner HL. Therapeutic anti-CD3 monoclonal antibodies: from bench to bedside. Immunotherapy. 2016 Jul;8(8):889-906. doi: 10.2217/imt-2016-0049. Epub 2016 May 10.
PubMed 27161438Krasemann S, Madore C, Cialic R, Baufeld C, Calcagno N, El Fatimy R, Beckers L, O'Loughlin E, Xu Y, Fanek Z, Greco DJ, Smith ST, Tweet G, Humulock Z, Zrzavy T, Conde-Sanroman P, Gacias M, Weng Z, Chen H, Tjon E, Mazaheri F, Hartmann K, Madi A, Ulrich JD, Glatzel M, Worthmann A, Heeren J, Budnik B, Lemere C, Ikezu T, Heppner FL, Litvak V, Holtzman DM, Lassmann H, Weiner HL, Ochando J, Haass C, Butovsky O. The TREM2-APOE Pathway Drives the Transcriptional Phenotype of Dysfunctional Microglia in Neurodegenerative Diseases. Immunity. 2017 Sep 19;47(3):566-581.e9. doi: 10.1016/j.immuni.2017.08.008.
PubMed 28930663Keymeulen B, Vandemeulebroucke E, Ziegler AG, Mathieu C, Kaufman L, Hale G, Gorus F, Goldman M, Walter M, Candon S, Schandene L, Crenier L, De Block C, Seigneurin JM, De Pauw P, Pierard D, Weets I, Rebello P, Bird P, Berrie E, Frewin M, Waldmann H, Bach JF, Pipeleers D, Chatenoud L. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med. 2005 Jun 23;352(25):2598-608. doi: 10.1056/NEJMoa043980.
PubMed 15972866Ilan Y, Zigmond E, Lalazar G, Dembinsky A, Ben Ya'acov A, Hemed N, Kasis I, Axelrod E, Zolotarov L, Klein A, El Haj M, Gandhi R, Baecher-Allan C, Wu H, Murugaiyan G, Kivisakk P, Farez MF, Quintana FJ, Khoury SJ, Weiner HL. Oral administration of OKT3 monoclonal antibody to human subjects induces a dose-dependent immunologic effect in T cells and dendritic cells. J Clin Immunol. 2010 Jan;30(1):167-77. doi: 10.1007/s10875-009-9323-7. Epub 2009 Sep 16.
PubMed 19756989Faridar A, Thome AD, Zhao W, Thonhoff JR, Beers DR, Pascual B, Masdeu JC, Appel SH. Restoring regulatory T-cell dysfunction in Alzheimer's disease through ex vivo expansion. Brain Commun. 2020 Jul 20;2(2):fcaa112. doi: 10.1093/braincomms/fcaa112. eCollection 2020.
PubMed 32954348Dansokho C, Ait Ahmed D, Aid S, Toly-Ndour C, Chaigneau T, Calle V, Cagnard N, Holzenberger M, Piaggio E, Aucouturier P, Dorothee G. Regulatory T cells delay disease progression in Alzheimer-like pathology. Brain. 2016 Apr;139(Pt 4):1237-51. doi: 10.1093/brain/awv408. Epub 2016 Feb 1.
PubMed 26912648Colonna M, Butovsky O. Microglia Function in the Central Nervous System During Health and Neurodegeneration. Annu Rev Immunol. 2017 Apr 26;35:441-468. doi: 10.1146/annurev-immunol-051116-052358. Epub 2017 Feb 9.
PubMed 28226226Ciccocioppo F, Lanuti P, Pierdomenico L, Simeone P, Bologna G, Ercolino E, Buttari F, Fantozzi R, Thomas A, Onofrj M, Centonze D, Miscia S, Marchisio M. The Characterization of Regulatory T-Cell Profiles in Alzheimer's Disease and Multiple Sclerosis. Sci Rep. 2019 Jun 19;9(1):8788. doi: 10.1038/s41598-019-45433-3.
PubMed 31217537
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Foralumab Safety and Modulation of Microglial Activation Evaluated by PET Imaging in Patients With Early Symptomatic Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT06489548
- Acronym / sponsor ID
- 2023P003329
- Keywords
- Alzheimers, Dementia, Mild Cognitive Impairment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Tiziana Life Sciences LTD
- Study start
- 16 Sep 2025 (actual)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 8 Jul 2024 (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.
This phase 2a study will research the safety and tolerability of Foralumab, a human anti-CD3 antibody. An antibody is a molecule secreted by the immune system. These molecules are created to identify a specific pathogen. Previous data on experimental mice has suggested that Foralumab increases the immune system activity in the brain to reduce the inflammation of microglia, the brain's main immune cells. This combination of increased immune reactivity and less microglia inflammation may improve the immune response throughout the brain. Alzheimer's disease and other forms of dementia are characteristically known for the build-up of certain proteins in the brain. This trial will evaluate whether nasal Foralumab can improve cognition in participants with mild cognitive impairment due to early Alzheimer's or dementia.
The trial will ask participants to administer Foralumab nasally three times a week for eight weeks. The administration will occur intermittently, with breaks between each dosing cycle. Participants will also receive brain scans (Amyloid PET and MRI), undergo cognitive testing, blood draws, and physical, neurological, and nasal exams. Volunteers are expected to remain in the trial for six months.
Detailed description
Preliminary data has shown that Foralumab, a human anti-CD3 antibody, may improve cognition in APP/PS1and 3xTg mouse models of AD. Nasal Foralumab has been given to healthy volunteers with progressive multiple sclerosis (MS). When given nasally for five consecutive days, doeses up to 250 µg are well-tolerated.
This is a randomized, double-blind, placebo-controlled study assessing two dose levels of nasal foralumab (50 µg/dosing day and 100 µg/dosing day) or placebo, given in three-week "treatment cycles". A treatment cycle is defined as Investigational Product (IP) dosing on Monday, Wednesday, and Friday for two consecutive weeks, followed by a one-week pause in dosing or a "rest week." All treatment cycles follow the identical dosing regimen. Randomization will be 3:1 Active to Placebo.
Two cohorts of eight (8) subjects each will be enrolled in this study, and enrollment in these cohorts will be staggered. Both cohorts, Cohort A and Cohort B, will consist of six (6) subjects who will complete three months (4 cycles) of active treatment and two (2) subjects who receive Placebo treatment. Enrollment into Cohort B may begin once all subjects in Cohort A complete 2 cycles of treatment.
Subjects will be screened and enrolled at the Center for Alzheimer Research and Treatment (CART). Initial treatment visits will occur in the Center for Clinical Investigation (CCI) with follow-up visits occurring in CART. Both centers are in the Building for Transformative Medicine, Brigham and Women's Hospital (BWH) at 60 Fenwood Road, Boston, MA 02115.
Subjects will undergo screening procedures, including laboratory studies (hematology, clinical chemistry, CRP, EBV serology, HIV testing, Hepatitis B and Hepatitis C), vital signs, cognitive testing, and a complete physical exam by the physician investigator or a mid-level practitioner, and a detailed neurologic examination performed by a neurologist. Each subject must have normal laboratory tests, or results must be in a clinically acceptable range in the opinion of the Investigator. An additional screening visit will consist of an amyloid PET scan (if subjects do not already have those results prior to screening). Prior to each treatment cycle and at the end of treatment, an ENT physician will conduct a nasal exam and safety blood labs will be collected. At baseline and end of treatment, each subject will have blood samples collected for immunological study and undergo an MRI and a microglial PET scan. Blood samples for immunologic studies will be collected at baseline and after 3 months of treatment. A lumbar puncture will be performed at the screening visit and after 3 months of treatment to assess for changes in amyloid and tau.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: This cohort of subjects will receive 100µg/dosing day vs. placebo throughout the study. | Active comparator | Drug: Foralumab TZLS-401 100 µgThis group will receive a nasal spray three times a week for two weeks, followed by a one-week rest. That cycle will occur three more times for a total of three months of drug intervention. |
| Arm B: This cohort of subjects will receive 50µg/dosing day vs. placebo throughout the study. | Active comparator | Drug: Foralumab TZLS-401 50 µgThis group will receive a nasal spray three times a week for two weeks, followed by a one-week rest. That cycle will occur three more times for a total of three months of drug intervention. |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- The Sponsor will rely on NIA-AA Alzheimer's Disease Diagnostic Guidelines for Early Symptomatic Alzheimer's Disease (AD) with a 20-30 MMSE score, Clinical Dementia Rating (CDR) global score of 0.5 or 1, and impaired memory performance below an education adjusted cut-off score on the Logical Memory II subscale delayed paragraph recall (LM-IIa) of the Wechsler Memory Scale- Revised (WMS-R) (127) (≥16 years: ≤8; 8-15 years: ≤4; 0-7 years: ≤2).
- Age between 60 and 85 years (inclusive).
- Good general health with no disease likely to interfere with the study assessments.
- On a stable medication regimen for eight weeks prior to the study and is anticipated to remain stable during the study.
- Subject is not pregnant, lactating, or of childbearing potential (i.e., women must be two years post-menopausal or surgically sterile). If a woman is of childbearing potential, her partner must use barrier contraception throughout the study.
Key exclusion criteria (14 listed)
- Any significant neurologic disease including Parkinson's disease, stroke, multiinfarct dementia, frontotemporal dementia, Lewy body dementia, normal pressure hydrocephalus, brain tumor, brain hemorrhage with persistent neurologic deficits, progressive supra-nuclear palsy, seizure disorder, multiple sclerosis, or history of significant head trauma followed by persistent neurologic deficits or known structural brain abnormalities.
- Clinically significant or unstable medical conditions, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic diseases.
- History of autoimmune disease.
- Current treatment with immunomodulatory or immunosuppressive drugs or corticosteroid administration by any route of administration (including nasal corticosteroids) within the past month.
- Major depressive disorder (within the past 1 year), or a history of bipolar disorder, or a history of schizophrenia.
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 |
|---|---|---|
| Foralumab TZLS-401 50 µgForalumab is a nasal anti-CD3 antibody. It will be administered in doses of 50 µg vs. placebo. | Drug | Arm B: This cohort of subjects will receive 50µg/dosing day vs. placebo throughout the study. |
| Foralumab TZLS-401 100 µgForalumab is a nasal anti-CD3 antibody. It will be administered in doses of 100 µg vs. placebo. | Drug | Arm A: This cohort of subjects will receive 100µg/dosing day vs. placebo throughout the study. |
Primary outcome
The number of adverse events in drug versus placebo groups.
Time frame: From baseline to the end of study, up to 20 weeks.
Establish the safety and tolerability of nasal foralumab dosing in subjects as a percentage of drug and placebo groups who experience adverse events.
Assessment of microglial function via PET scan using the ligand [18F]PBR06
Time frame: From baseline to end of study, up to 20 weeks.
The ligand [18F]PBR06 provides a quantification of microglial activation during a PET scan. The investigatorshope to use this tracer at the start and end of the study to examine how the use of Foralumab may affect microglial function.
Measure the effect of foralumab on the ratio of CD4/CD8 memory/naïve T cells biomarkers in blood
Time frame: From baseline to the end of treatment, up to 12 weeks.
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 12 Feb 2026.
- Background: PubMed 34603323Zhou R, Ji B, Kong Y, Qin L, Ren W, Guan Y, Ni R. PET Imaging of Neuroinflammation in Alzheimer's Disease. Front Immunol. 2021 Sep 16;12:739130. doi: 10.3389/fimmu.2021.739130. eCollection 2021.
- Background: PubMed 18941193Wu HY, Quintana FJ, Weiner HL. Nasal anti-CD3 antibody ameliorates lupus by inducing an IL-10-secreting CD4+ CD25- LAP+ regulatory T cell and is associated with down-regulation of IL-17+ CD4+ ICOS+ CXCR5+ follicular helper T cells. J Immunol. 2008 Nov 1;181(9):6038-50. doi: 10.4049/jimmunol.181.9.6038.
- Background: PubMed 21949026Toly-Ndour C, Lui G, Nunes MM, Bruley-Rosset M, Aucouturier P, Dorothee G. MHC-independent genetic factors control the magnitude of CD4+ T cell responses to amyloid-beta peptide in mice through regulatory T cell-mediated inhibition. J Immunol. 2011 Nov 1;187(9):4492-500. doi: 10.4049/jimmunol.1003953. Epub 2011 Sep 26.
- Background: PubMed 18510923Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008 May 30;133(5):775-87. doi: 10.1016/j.cell.2008.05.009.
- Background: PubMed 28739191Ogura M, Deng S, Preston-Hurlburt P, Ogura H, Shailubhai K, Kuhn C, Weiner HL, Herold KC. Oral treatment with foralumab, a fully human anti-CD3 monoclonal antibody, prevents skin xenograft rejection in humanized mice. Clin Immunol. 2017 Oct;183:240-246. doi: 10.1016/j.clim.2017.07.005. Epub 2017 Jul 21.
- Background: PubMed 34475873Moreira TG, Matos KTF, De Paula GS, Santana TMM, Da Mata RG, Pansera FC, Cortina AS, Spinola MG, Baecher-Allan CM, Keppeke GD, Jacob J, Palejwala V, Chen K, Izzy S, Healey BC, Rezende RM, Dedivitis RA, Shailubhai K, Weiner HL. Nasal Administration of Anti-CD3 Monoclonal Antibody (Foralumab) Reduces Lung Inflammation and Blood Inflammatory Biomarkers in Mild to Moderate COVID-19 Patients: A Pilot Study. Front Immunol. 2021 Aug 12;12:709861. doi: 10.3389/fimmu.2021.709861. eCollection 2021.
- Background: PubMed 27246324Mayo L, Cunha AP, Madi A, Beynon V, Yang Z, Alvarez JI, Prat A, Sobel RA, Kobzik L, Lassmann H, Quintana FJ, Weiner HL. IL-10-dependent Tr1 cells attenuate astrocyte activation and ameliorate chronic central nervous system inflammation. Brain. 2016 Jul;139(Pt 7):1939-57. doi: 10.1093/brain/aww113. Epub 2016 May 31.
- Background: PubMed 27161438Kuhn C, Weiner HL. Therapeutic anti-CD3 monoclonal antibodies: from bench to bedside. Immunotherapy. 2016 Jul;8(8):889-906. doi: 10.2217/imt-2016-0049. Epub 2016 May 10.
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- AmyvidTM Package Insert, 2012. United States Package Insert for florbetapir F18 Injection .Link provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Foralumab TZLS-401 50 µg and Foralumab TZLS-401 100 µg in people with Dementia and Alzheimers Disease, run by Brigham and Women's Hospital 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 8 inclusion and 14 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 12 Feb 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Gad Marshall, MD (617-525-6754, foralumab@mgb.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of adverse events in drug versus placebo groups. (time frame: From baseline to the end of study, up to 20 weeks.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06489548, which also lists 18 linked publications.
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 12 Feb 2026.