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

Mild Cognitive Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02423122
• Other study ID #: EIP-VX00-745-302
• Status: Completed
• Phase: Phase 2
• Start date: April 2015
• Est. completion date: September 2016

Study information

• Verified date: January 2018
• Source: EIP Pharma, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: September 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Cognitive Dysfunction
• Mild Cognitive Impairment
• Plaque, Amyloid

Intervention

Drug:
• VX-745
Orally-Active Selective P45 MAP Kinase inhibitor

Locations

Country	Name	City	State
Netherlands	Alzheimer Research Center, VU Medical Center	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
EIP Pharma, LLC

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Amyloid Plaque Burden by 11C-PiB PET	Percent change in global cortical amyloid specific PET signal (BPND)	Baseline compared to following 12 weeks' dosing with VX-745
Primary	Number of 11C-PiB Responders	Number of patients meeting protocol pre-specified definition of response: > 7% reduction in global cortical BPND	Day 84
Secondary	Wechsler Memory Scale (WMS) Immediate Recall Composite	WMS immediate-recall composite score consisted of the sum of the scores on Logical Memory I, Verbal Paired Associates I, and Visual Reproduction I. The composite score ranges from 0 to 136; with higher score indicating better performance.	Baseline to Day 84
Secondary	Wechsler Memory Scale (WMS) Delayed Recall Composite	WMS delayed-recall composite score at each testing sessions consisted of the sum of the scores on Logical Memory II, Verbal Paired Associates II, and Visual Reproduction II. The composite score ranges from 0 to 136; with higher scores indicating better performance.	Change from baseline to Day 84