Assessment of Foralumab Safety and Modulation of Microglial Activation in Alzheimer's Disease

NCT06489548 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2023P003329TILS-024
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Dementia; Mild Cognitive Impairment Due to Alzheimer's Disease; Alzheimers Disease

Keywords

Alzheimers; Dementia; Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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

  From baseline to the end of treatment, up to 12 weeks.

Study Arms (2)

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.

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.

Drug: Foralumab TZLS-401 50 µg

Interventions

Foralumab TZLS-401 50 µg DRUG

Foralumab is a nasal anti-CD3 antibody. It will be administered in doses of 50 µg vs. placebo.

Arm B: This cohort of subjects will receive 50µg/dosing day vs. placebo throughout the study.

Foralumab TZLS-401 100 µg DRUG

Foralumab is a nasal anti-CD3 antibody. It will be administered in doses of 100 µg vs. placebo.

Arm A: This cohort of subjects will receive 100µg/dosing day vs. placebo throughout the study.

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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)

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Tiziana Life Sciences LTD: collaborator

Study Sites (1)

Center for Alzheimer Research and Treatment, Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (18)

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Related Links

• AmyvidTM Package Insert, 2012. United States Package Insert for florbetapir F18 Injection .

MeSH Terms

Conditions

Dementia; Alzheimer Disease; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Tauopathies; Neurodegenerative Diseases; Cognition Disorders

Central Study Contacts

Gad Marshall, MD

CONTACT

617-525-6754; foralumab@mgb.org

Ryan de Lissovoy, BS

CONTACT

617-278-0831; foralumab@mgb.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Clinical Trials, Center for Alzheimer Research and Treatment

Study Record Dates

• First Submitted: May 28, 2024
• First Posted: July 8, 2024
• Study Start: September 16, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)