Clinical Pharmacology of p38 MAP Kinase Inhibitor, VX-745, in Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD

Phase 2

Completed

Conditions: Alzheimer's Disease

Interventions: Drug: VX-745

Registration Number: NCT02423200

Lead Sponsor: EIP Pharma Inc

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
VX-745 dose level 1	VX-745	Active Group 1: VX-745 dose level 1 twice daily
VX-745 dose level 2	VX-745	Active Group 1: VX-745 dose level 2 twice daily

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline to End of Treatment in Cerebrospinal Fluid Levels of Cytokines	Baseline and Day 42 of dosing with VX-745	Cytokines: Of nine cytokines assessed, only CSF IL-8 quantifiable at all time points. And so, only IL-8 levels are being reported herein. The analysis was exploratory and no statistical analysis was performed.

Secondary Outcome Measures

Name	Time	Method
Severe or Serious Adverse Events	At baseline and at each study visit during (days 1, 7, 14, 21, 28, 35 and 42) and after (day 51) dosing	Number of patients with severe or serious adverse events
Maximal CSF VX-745 Concentration	All samples with quantifiable CSF drug levels were included (n=12). Eight were obtained 3-hours post-dose, either on Day 1 (n=4) or Day 42 (n=4). 3 samples were at 6-hours post-dose on Day 42; and one was at 6-hours post-dose on Day 1.	Ratio fo CSF to plasma drug concentration at time matched time points. Samples taken
Episodic Memory Function	Change from baseline to Day 42	Total Recall in Hopkins Verbal Learning Test (HVLT). Range is 0-36, with increases in score indicating improvement in cognitive function.