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

February 10, 2026 updated by: Gad A. Marshall, MD, Brigham and Women's Hospital

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

16

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Center for Alzheimer Research and Treatment, Brigham and Women's Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Foralumab TZLS-401 100 µg
Foralumab is a nasal anti-CD3 antibody. It will be administered in doses of 100 µg vs. placebo.
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.
Drug: Foralumab TZLS-401 50 µg
Foralumab is a nasal anti-CD3 antibody. It will be administered in doses of 50 µg vs. placebo.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of adverse events in drug versus placebo groups.
Time Frame: From baseline to the end of study, up to 20 weeks.
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
Time Frame: From baseline to end of study, up to 20 weeks.
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
Time Frame: From baseline to the end of treatment, up to 12 weeks.
From baseline to the end of treatment, up to 12 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Collaborators

Tiziana Life Sciences LTD

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 16, 2025

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

May 28, 2024

First Submitted That Met QC Criteria

July 3, 2024

First Posted (Actual)

July 8, 2024

Study Record Updates

Last Update Posted (Actual)

February 12, 2026

Last Update Submitted That Met QC Criteria

February 10, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023P003329
  • TILS-024 (Other Identifier: FDA)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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