A PET Study of the Effects of p38 MAP Kinase Inhibitor, VX-745, on Amyloid Plaque Load in Alzheimer's Disease (AD)

A Clinical Study of Two Doses of a Selective p38 MAP Kinase Inhibitor, VX-745, to Evaluate the Effects of 12-Week Oral Twice-Daily Dosing on Amyloid Plaque Load as Assessed by Quantitative Dynamic 11C-PiB Positive Emission Tomography (PET) Amyloid Scanning

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.

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