A Study Assessing Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: Bryostatin 1; Placebo
Intervention description: The investigational drug product, bryostatin, is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution. Placebo is a sterile, pyrogen-free, lyophilized powder intended for IV infusion upon reconstitution and dilution.; The placebo is a sterile, pyrogen-free, lyophilized powder identical in appearance to the active drug, intended for IV infusion upon reconstitution and dilution.
Intervention MeSH terms: Bryostatin 1
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 147.0
Sex: All
Minimum age: 55 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      This is a randomized double-blind placebo-controlled study comparing different doses of
      bryostatin for the treatment of moderately severe to severe Alzheimer's disease. The study is
      15 weeks in duration, including a safety and efficacy evaluation 30 days after the last dose
      of study drug.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Written informed consent from caregiver and subject (if possible) or legally
             acceptable representative if different from caregiver

          -  Male and female subjects 55-85 years of age inclusive

          -  Cognitive deficit present for at least 2 years that meet the diagnostic criteria for
             probable Alzheimer's

          -  Mini Mental State Exam (MMSE-2) score of 4-15

          -  Patients must be able to perform at least one item on the Severe Impairment Battery
             Scale

          -  Neuroimaging (computerized tomography (CT) or Magnetic Resonance Imaging (MRI)) within
             the last 24 months consistent with a diagnosis of probable Alzheimer's disease (AD)

          -  Reliable caregiver(s) or informant(s) who attends the subject at least an average of 3
             hours or more per day for 3 or more days per week

          -  Adequate vision and motor function to comply with testing

          -  If taking drugs approved for treatment of Alzheimer's disease (e.g. cholinesterase
             inhibitors, memantine), must be on a stable dose for at least 3 months prior to entry
             into study and the dose must not change during the study unless a change is required
             due to an adverse event or a clinically significant change in the patient's status.

        Exclusion Criteria:

          -  Dementia due to any condition other than AD, including vascular dementia
             (Rosen-modified Hachinski lschemic score ≥ 5)

          -  Evidence of significant central nervous system (CNS) vascular disease on previous
             neuroimaging including but not limited to: cortical stroke, multiple infarcts,
             localized single infarcts in the thalamus, angular gyrus, multiple lacunar infarcts or
             extensive white matter injury

          -  Clinically significant neurologic disease or condition other than AD, such as cerebral
             tumor, chronic subdural fluid collections, Huntington's Disease, Parkinson's Disease,
             normal pressure hydrocephalus, or any other diagnosis that could interfere with
             assessment of safety and efficacy

          -  Evidence of clinically significant unstable cardiovascular, pulmonary, renal, hepatic,
             gastrointestinal, neurologic, or metabolic disease within the 6 months prior to
             enrollment

          -  Poorly controlled diabetes, at the discretion of the Principal Investigator

          -  Creatinine clearance (CL) of <45ml/min

          -  Use of an active Alzheimer's vaccine within 2 years prior to screening

          -  Use of a monoclonal antibody for treatment of AD within 1 year prior to screening

          -  Any medical or psychiatric condition that is likely to require initiation of
             additional medication or surgical intervention during the course of the study

          -  Use of an investigational drug within 30 days prior to screening

          -  Prior exposure to bryostatin, or known sensitivity to bryostatin or any ingredient in
             the study drug

          -  Any other concurrent medical condition, which in the opinion of the PI makes the
             subject unsuitable for the clinical study