A Phase 2b Clinical Study of the P38 Alpha Kinase Inhibitor Neflamapimod in Patients with Dementia with Lewy Bodies (DLB)

Prior treatment

• History of previous neurosurgery to the brain within the past five years.
• Suicidality, defined as active suicidal thoughts within 6 months before Screening or at Baseline or history of suicide attempt in previous 2 years, or, in the Investigator’s opinion, at serious risk of suicide.
• Ongoing major and active psychiatric disorder and/or other concurrent medical condition that, in the opinion of the Investigator, might compromise safety and/or compliance with study requirements.
• Diagnosis of alcohol or drug abuse within the previous 2 years.
• Participated in a study of an investigational drug less than six weeks or 5 half-lives of an investigational drug, whichever is longer, before enrollment in this study.

Other illness

• Diagnosis of any other ongoing central nervous system (CNS) condition other than DLB).
• Plasma ptau181 result above the threshold that indicates evidence of pathology associated with Alzheimer’s disease at Screening.
• Poorly controlled clinically significant medical illness or other disease that would interfere with assessment of drug safety.
• Known human immunodeficiency virus, hepatitis B, or active hepatitis C virus infection.

Lab values

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 × the upper limit of normal (ULN), total bilirubin >1.5 × ULN, and/or International Normalized Ratio (INR) >1.5.

Other

• Unwilling or unable to adhere to contraception requirements specified in the protocol.
• If female has a positive pregnancy test result during Screening and/or is unwilling or unable to adhere to the contraception requirements specified in the protocol.

• Men and women aged ≥55 years.
• Subject is willing and able to provide written informed consent.
• Probable DLB by consensus criteria, including a positive DaTscan™. If the DaTscan is negative, but the subject has historical polysomnography (PSG)-verified REM sleep behavioral disorder (RBD), this will also qualify as probable DLB.
• CDR Global Score less than 2.0 at Screening.
• If the patient is currently receiving cholinesterase inhibitor therapy, the patient must have received such therapy for greater than 3 months and on a stable dose for at least 6 weeks at the time of randomization. If the patient is not currently receiving cholinesterase inhibitor therapy, that therapy must have been discontinued at least 3 months prior to randomization.
• Normal or corrected eyesight and auditory abilities, sufficient to perform all aspects of the cognitive and functional assessments.
• No history of learning difficulties that may interfere with their ability to complete the cognitive tests.
• Received vaccination for SARS-CoV-19 unless medical contraindications prevent being vaccinated or has a history of natural infection.
• Must have reliable informant or caregiver.