Assessment of Foralumab Safety and Modulation of Microglial Activation in Alzheimer's Disease
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age60-85
SponsorBrigham and Women's Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Current treatment with immunomodulatory or immunosuppressive drugs or corticosteroid administration by any route of administration (including nasal corticosteroids) within the past month.
Trial design
Design model
Parallel
Treatments tested in this trial
Foralumab TZLS-401 50 µg
DrugForalumab is a nasal anti-CD3 antibody. It will be administered in doses of 50 µg vs. placebo.
Foralumab TZLS-401 100 µg
DrugForalumab is a nasal anti-CD3 antibody. It will be administered in doses of 100 µg vs. placebo.
Treatment groups
16 Participants
are divided into 2 treatment groupsGroup A: Arm A: This cohort of subjects will receive 100µg/dosing day vs. placebo throughout the study.Active comparator 1 intervention
Group B: Arm B: This cohort of subjects will receive 50µg/dosing day vs. placebo throughout the study.Active comparator 1 intervention
Trial outcomes
Primary outcomes
1
The number of adverse events in drug versus placebo groups.
Establish the safety and tolerability of nasal foralumab dosing in subjects as a percentage of drug and placebo groups who experience adverse events.
Time frame
From baseline to the end of study, up to 20 weeks.2
Assessment of microglial function via PET scan using the ligand [18F]PBR06
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.
Time frame
From baseline to end of study, up to 20 weeks.3
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.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Brigham and Women's Hospital
Lead sponsor
Tiziana Life Sciences LTD
Collaborator
Source ClinicalTrials.gov