Recruiting
Phase 2

Foralumab

Sponsor:

Brigham and Women's Hospital

Code:

NCT06489548

Conditions

Dementia

Alzheimers Disease

Mild Cognitive Impairment Due to Alzheimer's Disease

Eligibility Criteria

Sex: All

Age: 60 - 70+

Healthy Volunteers: Not accepted

Interventions

Foralumab TZLS-401 50 µg

Foralumab TZLS-401 100 µg

Study Details

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

Alzheimers Disease

Mild Cognitive Impairment Due to Alzheimer's Disease

Study ID

NCT06489548

Start date

Sep 16, 2025

Status verified date

Feb, 2026

Completion date

Dec, 2026

Anticipated

Primary completion date

Jun, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 60 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. 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).
2. Age between 60 and 85 years (inclusive).
3. Good general health with no disease likely to interfere with the study assessments.
4. On a stable medication regimen for eight weeks prior to the study and is anticipated to remain stable during the study.
5. 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.
6. 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.
7. Ability to understand and provide informed consent.
8. Has availability of a study partner who has regular contact with the participant and knows him/her well.

Exclusion Criteria:

1. 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.
2. Clinically significant or unstable medical conditions, including uncontrolled hypertension, uncontrolled diabetes, or significant cardiac, pulmonary, renal, hepatic, endocrine, or other systemic diseases.
3. History of autoimmune disease.
4. Current treatment with immunomodulatory or immunosuppressive drugs or corticosteroid administration by any route of administration (including nasal corticosteroids) within the past month.
5. Major depressive disorder (within the past 1 year), or a history of bipolar disorder, or a history of schizophrenia.
6. History of alcohol or substance abuse or dependence within the past two years.
7. History of malignancy within the past 3 years.
8. Clinically significant abnormalities in screening laboratories (defined as greater than mild on the FDA's vaccine toxicity grading scale).
9. Participation in another clinical trial of an investigational drug concurrently or within the past 30 days.
10. Low affinity TSPO binders (for PET ligand \[18F\]PBR06) determined by having a Thr/Thr polymorphism in the TSPO gene at screening.
11. Sensitivity to florbetapir F18.
12. Active COVID-19 disease.
13. Amyloid-negative PET scan.
14. COVID-19 vaccine within the past ten days or any other vaccine within the past seven days (at dosing)

Study Design

Enrollment

16 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

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.

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

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.

Interventions

Foralumab TZLS-401 50 µg

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

Foralumab TZLS-401 100 µg

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

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. ]
  • Assessment of microglial function via PET scan using the ligand [18F]PBR06 [ Time Frame: 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 [ Time Frame: From baseline to the end of treatment, up to 12 weeks. ]

Central Contacts and Locations

Central contacts

Locations

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

Recruiting

Boston, Massachusetts, United States, 02115

Contacts

More Information

Sponsor

Brigham and Women's Hospital

Last update posted

Feb 12, 2026

Last verified

Feb, 2026

Keywords

  • Alzheimers
  • Dementia
  • Mild Cognitive Impairment

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Brigham and Women's Hospital on 2026-02-12.