Efficacy and Safety of GSK4527226 [AL101] in Participants With Early Alzheimer's Disease

Exclusion Criteria

• •Participant has evidence of any neurological condition other than AD that may contribute to cognitive impairment.
• •History or presence of vascular disease that has the potential to affect cognitive function.
• •History or presence of stroke within the past 1 year or recent transient ischemic attack within 180 days before screening.
• •History of severe, clinically significant central nervous system (CNS) trauma.
• •History or presence of intracranial tumor.
• •Presence of ongoing infection(s) that may affect brain function, or history of infections that resulted in neurologic sequelae.
• •History of primary psychiatric diagnosis that the investigator considers may interfere with study assessments.
• •Columbia Suicide Severity Rating Scale (C-SSRS) suicidal ideation Type 4 or 5, suicidal behaviour or has been assessed to be at risk of suicide, in the opinion of the investigator within 6 months before screening, at screening, or at the Baseline visit, or has been hospitalized or treated for suicidal behaviour in the past 2 years.
• •Participant has history of alcohol and/or moderate to severe substance use disorder within the past 2 years
• •Magnetic resonance imaging (MRI) evidence based on central read of:
• •1. \>3 lacunar infarcts.
• •2. Stroke involving a major vascular territory, severe small vessel, or white matter disease.
• •3. Any territorial /cortical/other infarct \>1 cubic centimetre (cm\^3).
• •4. White matter hyperintense lesions on the FLAIR sequence that correspond to an overall Fazekas score of 3
• •5. \>4 microhaemorrhages.
• •6. Any areas of superficial (leptomeningeal) hemosiderosis.
• •7. A single macro-hemorrhage greater than 10 millimetres (mm) at greatest diameter.
• •8. Vasogenic edema.
• •9. Cerebral contusion, encephalomalacia, aneurysms, vascular malformations, or infective lesions.
• •10. Space occupying lesions or brain tumors.
• •11. Significant cerebral vascular pathology
• •12. Hydrocephalus/Normal pressure hydrocephalus.
• •13. Other MRI findings contraindicating participation in the study such as subarachnoid hemorrhage.
• •History suggestive of exposure to, or past tuberculosis (TB) infection should undergo screening for TB disease.
• •Chronic active immune disorder requiring systemic immunosuppressive therapy within 6 months prior to Screening.
• •Screening serum vitamin B12 concentration \< Lower limit of normal (LLN) or in the low normal range
• •Folate \<LLN or Thyroid-stimulating hormone (TSH) \> Upper limit of normal (ULN)
• •Hemoglobin A1c \>8 percentage (%) or poorly controlled diabetes during the last 12 weeks
• •History of cancer
• •Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins
• •Planned surgery during the study which requires general, spinal, or epidural anesthesia that would take place during the study.
• •Known genetic predisposition for clotting disorder or hemorrhagic disease.
• •Key exclusionary medications include:
• •* Antipsychotics, opiates/opioids, cannabinoids, hypnotics, antidepressants, mood stabilizers, or stimulants that are used on a chronic basis, are exclusionary if not consistent with the following rule: treatment has to have been at a stable dose for at least 4 weeks before screening and should remain stable during the study
• •* Any biologic drugs with systemic exposure, whether investigational or approved, used within 6 months before screening Any disease modification drug for AD, such as aducanumab and lecanemab, whether investigational or approved, used within 6 months before screening.
• •* Anticoagulation medications within 90 days of screening and during the study
• •* Systemic immunosuppressive therapy within 6 months before screening and during the study.