A PET Study of the Effects of p38 MAP Kinase Inhibitor, VX-745, on Amyloid Plaque Load in Alzheimer's Disease (AD)
Condition: Alzheimer's Disease; Mild Cognitive Impairment
MeSH terms: Alzheimer Disease; Plaque, Amyloid; Cognitive Dysfunction
Intervention: VX-745
Intervention description: Orally-Active Selective P45 MAP Kinase inhibitor
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 16.0
Sex: All
Minimum age: 60 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      This study will assess the effects of administration of VX-745 for 12 weeks on amyloid plaque
      burden in Alzheimer's disease (AD). Subjects who meet entry criteria will undergo 11C-PiB
      (Carbon-11-labeled Pittsburgh Compound B) positron emission tomography (PET) at baseline and
      after 45 days of dosing with VX-745. Cognitive testing will also be conducted at baseline and
      day 45.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to provide informed consent

          -  Diagnosis of mild cognitive impairment (MCI) due to probable AD or of mild AD

          -  MMSE range: 20 to 28

          -  Evidence of amyloid pathology by amyloid PET scan

          -  Participants may be taking medications for AD, provided that the dose of these
             medications has been stable for >3 months

          -  Proficiency in Dutch and adequate visual and auditory abilities to be able to perform
             all aspects of the cognitive and functional tests

          -  Adequate visual and auditory abilities to perform all aspects of the cognitive and
             functional assessments.

        Exclusion Criteria:

          -  Evidence of neurodegenerative disease other than AD

          -  Inability for any reason to undergo PET and fMRI scans (including notably: history of
             allergic reaction of any severity to 11C-PiB injection; pacemaker, vascular stent or
             stent graft)

          -  Psychiatric disorder that would compromise ability to comply with study requirements

          -  Significant cardiovascular, pulmonary, renal, liver, infectious disease, immune
             disorder or metabolic/endocrine disorders or other disease that would preclude
             treatment with p38 MAP kinase inhibitor and/or assessment of drug safety and efficacy

          -  Recent (<90 days) changes to AD medications prescribed for cognitive reasons or with
             the potential to impact cognition

          -  Participation in a study of an investigational drug less than 6 months or 5 half-lives
             of the investigational drug, whichever is longer, before enrollment in the study

          -  Male subjects with female partner of child-bearing potential who are unwilling or
             unable to adhere to contraception requirements

          -  Female subjects who have not reached menopause or have not had a hysterectomy or
             bilateral oophorectomy/salpingoophorectomy

          -  Positive urine or serum pregnancy test or plans desires to become pregnant during the
             course of the trial

          -  Any factor deemed by the investigator to be likely to interfere with study conduction