Clinical Pharmacology of p38 MAP Kinase Inhibitor, VX-745, in Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Intervention: VX-745
Intervention description: Orally-active P38 MAP kinase alpha-selective 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 VX-745 on markers of disease in the central nervous
      system of patients with MCI due to AD or with mild AD. The study will also evaluate the
      safety and tolerability of VX-745 in these patients during 6 weeks of dosing, as well as the
      plasma and cerebrospinal fluid concentrations of VX-745 during dosing.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 60 - 85 (inclusive)

          -  Willing and able to provide informed consent

          -  Clinical presentation consistent with MCI due to AD or of mild AD

               -  Gradual progressive decline in memory function over >6 months

               -  Amnestic presentation on neuropsychological testing with rapid forgetting (%
                  reduction 1.5 standard deviations below the mean)

               -  Clinical Dementia Rating (CDR) Sum of Box (SOB) score ≥0.5

               -  Mini-Mental State Examination (MMSE) range: 20 to 30

          -  Brain hypometabolism by 18F-2-fluoro-2-deoxyglucose (FDG)-PET

          -  Participants may be taking medications for AD, provided that the dose of these
             medications has been stable for >3 months.

        Exclusion Criteria:

          -  Evidence of neurodegenerative disease other than AD

          -  Inability for any reason to undergo MRI scans (e.g. pacemaker, vascular stent or stent
             graft). Patients who require sedation for screening procedures such as MRI may receive
             a short-acting sedative.

          -  Psychiatric disorder that would compromise ability to comply with study requirements

          -  History of cancer within the last 5 years, except basal cell carcinoma, non-squamous
             skin carcinoma, prostate cancer or carcinoma in situ with no significant progression
             over the past 2 years

          -  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

          -  Psychotropic drugs taken within 1 month. Anticoagulant drugs taken within 1 week.

          -  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

          -  Donation of >500 mL of blood or blood products within 2 months

          -  History of alcohol and/or illicit drug abuse within 6 months.

          -  Infection with hepatitis A, B or C or HIV.

          -  Any factor deemed by the investigator to be likely to interfere with study conduction