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

Prior treatment

• Current treatment with immunomodulatory or immunosuppressive drugs or corticosteroid administration by any route of administration (including nasal corticosteroids) within the past month.
• 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.

Other illness

• 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.
• 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.
• Active COVID-19 disease.
• COVID-19 vaccine within the past ten days or any other vaccine within the past seven days (at dosing)

Other

• 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.
• Amyloid-negative PET scan.

• 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.