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

Plain English Summary

Assessment of Foralumab Safety and Modulation of Microglial Activation in Alzheimer's Disease is a Phase 2 clinical trial sponsored by Brigham and Women's Hospital studying Dementia, Alzheimers Disease, Mild Cognitive Impairment Due to Alzheimer's Disease. This trial tests a nasal spray called Foralumab to see if it's safe and can help reduce brain inflammation in people with early Alzheimer's. It is for individuals aged 60-85 with early symptomatic Alzheimer's disease, confirmed by specific cognitive tests and a brain scan. Participants will use the nasal spray three times a week for eight weeks, with breaks, and undergo brain scans, cognitive tests, and medical exams over six months. Alternative treatments for early Alzheimer's include medications to manage symptoms and lifestyle changes, but this trial explores a new approach targeting brain inflammation. The trial aims to enroll 16 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are between 60 and 85 years old and have been diagnosed with early Alzheimer's disease, showing memory problems and specific brain scan results. You cannot join if you have other significant neurological diseases, serious unstable medical conditions, a history of autoimmune disease, or certain mental health conditions. You must be in good general health and on stable medications for at least eight weeks before the trial. Women who can become pregnant must have a partner who agrees to use barrier contraception throughout the study. This trial is studying Dementia, Alzheimers Disease, Mild Cognitive Impairment Due to Alzheimer's Disease, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes will show if the nasal spray is safe by tracking side effects, and if it can reduce inflammation in the brain and positively affect immune cells in the blood, which may indicate a The specific primary outcome measures are: The number of adverse events in drug versus placebo groups. (From baseline to the end of study, up to 20 weeks.); Assessment of microglial function via PET scan using the ligand [18F]PBR06 (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 (From baseline to the end of treatment, up to 12 weeks.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial is important because it investigates a novel nasal antibody treatment aimed at reducing brain inflammation, a key factor in Alzheimer's, potentially offering a new way to manage the disease Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Dementia, Alzheimers Disease, Mild Cognitive Impairment Due to Alzheimer's Disease, where improved treatment options are needed.

Investor Insight

This Phase 2a trial for an early Alzheimer's treatment targeting neuroinflammation represents a significant area of unmet medical need, with a large market potential and a competitive landscape focuse Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the potential benefits and risks of Foralumab, how it will be administered, and what tests will be performed. Be prepared for regular visits for nasal spray administration, brain scans (PET and MRI), cognitive tests, blood draws, and physical/neurological exams. Ensure you have a reliable study partner who can accompany you to appointments and help monitor your condition. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 16 participants

Interventions

• DRUG: Foralumab TZLS-401 50 µg — Foralumab is a nasal anti-CD3 antibody. It will be administered in doses of 50 µg vs. placebo.
• DRUG: Foralumab TZLS-401 100 µg — Foralumab is a nasal anti-CD3 antibody. It will be administered in doses of 100 µg vs. placebo.

Primary Outcomes

• The number of adverse events in drug versus placebo groups. (From baseline to the end of study, up to 20 weeks.)
• Assessment of microglial function via PET scan using the ligand [18F]PBR06 (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 (From baseline to the end of treatment, up to 12 weeks.)

Full 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)

Trial Locations

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

Frequently Asked Questions

Related Conditions

• Alzheimer's Disease
• Dementia
• Mild Cognitive Impairment
• Neuroinflammation
• Autoimmune Diseases
• Immunology
• Neurology
• Geriatrics
• Cognitive Disorders
• Neurodegenerative Diseases

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