Clinical trial NCT02423122: A PET Study of the Effects of p38 MAP Kinase Inhibitor, VX-745, on Amyloid Plaque Load in Alzheimer's Disease (AD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alzheimer's Disease
Mild Cognitive Impairment
Lead sponsor: EIP Pharma Inc
Sponsor class: INDUSTRY
First posted: 2015-04-22
Enrollment: 16
Sex: ALL
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Percent Change From Baseline in Amyloid Plaque Burden by 11C-PiB PET
timeFrame: Baseline compared to following 12 weeks' dosing with VX-745
measure: Number of 11C-PiB Responders
timeFrame: Day 84
Secondary outcomes:
measure: Wechsler Memory Scale (WMS) Immediate Recall Composite
timeFrame: Baseline to Day 84
measure: Wechsler Memory Scale (WMS) Delayed Recall Composite
timeFrame: Change from baseline to Day 84
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Alzheimer Research Center, VU Medical Center
Study officials:
affiliation: Alheimer Research Center, VU medisch centrum
name: Philip Scheltens, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tormahlen NM, Martorelli M, Kuhn A, Maier F, Guezguez J, Burnet M, Albrecht W, Laufer SA, Koch P. Design and Synthesis of Highly Selective Brain Penetrant p38alpha Mitogen-Activated Protein Kinase Inhibitors. J Med Chem. 2022 Jan 27;65(2):1225-1242. doi: 10.1021/acs.jmedchem.0c01773. Epub 2021 May 11.