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

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.