Nasal foralumab to reduce brain inflammation in early Alzheimer’s

Assessment of Foralumab Safety and Modulation of Microglial Activation Evaluated by PET Imaging in Patients With Early Symptomatic Alzheimer's Disease

This trial will test whether nasal foralumab, given three times a week, can reduce brain immune inflammation and improve thinking in people aged 60–85 with mild cognitive impairment from early Alzheimer’s disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 60 Years to 85 Years
• Sex: All
• Sponsor: Brigham and Women's Hospital (Academic / other)
• Drugs / interventions: Foralumab, CART
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT06489548 on ClinicalTrials.gov

What this trial studies

This randomized, double-blind, placebo-controlled Phase 2a study tests two dose levels of intranasal foralumab (50 µg and 100 µg dosing days) versus placebo using a 3:1 randomization. Dosing is given in repeated three-week cycles (two weeks of Monday/Wednesday/Friday dosing followed by one rest week) over approximately three months, with two staggered cohorts of eight subjects each. The trial focuses on safety and tolerability and will measure effects on microglial activation and cognition in amyloid-positive participants meeting early symptomatic AD criteria. All screening and visits occur at the Center for Alzheimer Research and Treatment and the Center for Clinical Investigation at Brigham and Women’s Hospital in Boston.

Who should consider this trial

Good fit: Ideal candidates are amyloid-positive adults aged 60–85 with mild cognitive impairment due to early Alzheimer’s, MMSE 20–30, CDR 0.5–1, and impaired delayed paragraph recall meeting the study cutoffs.

Not a fit: People who are amyloid-negative, have more advanced dementia, are outside the age range, or have unstable medical conditions are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, nasal foralumab could lower microglial inflammation and lead to improved cognition in people with early Alzheimer’s.

How similar studies have performed: Preclinical mouse models showed cognitive improvement and nasal foralumab was well tolerated in small human MS volunteer studies, but the approach has not yet shown clear cognitive benefit in Alzheimer’s patients.

Eligibility criteria

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)

Where this trial is running

Boston, Massachusetts

• Center for Alzheimer Research and Treatment, Brigham and Women's Hospital — Boston, Massachusetts, United States (Recruiting)

Study contacts

• Study coordinator: Gad Marshall, MD

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