Cognitive Effects of Oral p38 Alpha Kinase Inhibitor Neflamapimod in Dementia With Lewy Bodies
Condition: Dementia With Lewy Bodies (DLB)
MeSH terms: Dementia; Lewy Body Disease
Intervention: Neflamapimod
Intervention description: Double-Blind, Placebo-Controlled
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 91.0
Sex: All
Minimum age: 55 Years
Healthy volunteers: No

Summary:

      This is a Phase 2, multi-center, randomized, double-blind, placebo-controlled,
      proof-of-principle study of neflamapimod versus matching placebo (randomized 1:1)
      administered with food for 16 weeks in subjects with DLB. The primary objective is to
      evaluate the effect of neflamapimod on cognitive function as assessed in a study-specific
      Cogstate Neuropsychological Test Battery (NTB). Secondary endpoints include the Clinical
      Dementia Rating Scale-Sum of Boxes (CDR-SB), Mini-Mental State Examination (MMSE),
      Neuropsychiatric Inventory (NPI-10), Timed Up and Go Test, and electroencephalogram (EEG) as
      a potential biomarker for DLB.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Men and women aged ≥55 years.

          2. Subject or subject's legally authorized representative is willing and able to provide
             written informed consent.

          3. Probable DLB and identified cognitive deficits, according to current consensus
             criteria (McKeith et al, 2017), specifically one core clinical feature and a positive
             DaTscan. If a negative DaTscan, but the subject has historical PSG-verified RBD, the
             subject would also qualify.

          4. MMSE score of 15-28, inclusive, during Screening.

          5. Currently receiving cholinesterase inhibitor therapy, having received such therapy for
             greater than 3 months and on a stable dose for at least 6 weeks at the time of
             randomization. Except for reducing the dose for tolerability reasons, the dose of
             cholinesterase inhibitor may not be modified during the study.

          6. Normal or corrected eye sight and auditory abilities, sufficient to perform all
             aspects of the cognitive and functional assessments.

          7. No history of learning difficulties that may interfere with their ability to complete
             the cognitive tests.

          8. Must have reliable informant or caregiver.

        Exclusion Criteria:

          1. Diagnosis of any other ongoing central nervous system (CNS) condition other than DLB,
             including, but not limited to, post-stroke dementia, vascular dementia, Alzheimer's
             disease (AD), or Parkinson's disease (PD).

          2. Suicidality, defined as active suicidal thoughts within 6 months before Screening or
             at Baseline, defined as answering yes to items 4 or 5 on the C-SSRS, or history of
             suicide attempt in previous 2 years, or, in the Investigator's opinion, at serious
             risk of suicide.

          3. 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.

          4. Diagnosis of alcohol or drug abuse within the previous 2 years.

          5. Poorly controlled clinically significant medical illness, such as hypertension (blood
             pressure >180 mmHg systolic or 100 mmHg diastolic); myocardial infarction within 6
             months; uncompensated congestive heart failure or other significant cardiovascular,
             pulmonary, renal, liver, infectious disease, immune disorder, or metabolic/endocrine
             disorders or other disease that would interfere with assessment of drug safety.

          6. 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.

          7. Known human immunodeficiency virus, hepatitis B, or active hepatitis C virus
             infection.

          8. Participated in a study of an investigational drug less than 3 months or 5 half-lives
             of an investigational drug, whichever is longer, before enrollment in this study.

          9. History of previous neurosurgery to the brain.

         10. If male with female partner(s) of child-bearing potential, unwilling or unable to
             adhere to contraception requirements specified in the protocol.

         11. If female who has not has not reached menopause >1 year previously or has not had a
             hysterectomy or bilateral oophorectomy/salpingo-oophorectomy, has a positive pregnancy
             test result during Screening and/or is unwilling or unable to adhere to the
             contraception requirements specified in the protocol.