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

NCT02423122 | Completed Phase 2 Results

• 1 other identifier: EIP-VX00-745-302
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer's Disease; Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (2)

• 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

• Number of 11C-PiB Responders

  Number of patients meeting protocol pre-specified definition of response: \> 7% reduction in global cortical BPND

  Day 84

Secondary Outcomes (2)

• Wechsler Memory Scale (WMS) Immediate Recall Composite

  Baseline to Day 84

• Wechsler Memory Scale (WMS) Delayed Recall Composite

  Change from baseline to Day 84

Study Arms (2)

VX-745 dose 1

EXPERIMENTAL

Active Group 1: VX-745 40 mg twice daily

Drug: VX-745

VX-745 dose 2

EXPERIMENTAL

Active Group 2: VX-745 125 mg twice daily

Drug: VX-745

Interventions

VX-745 DRUG

Orally-Active Selective P45 MAP Kinase inhibitor

VX-745 dose 1; VX-745 dose 2

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• EIP Pharma Inc: lead

Study Sites (1)

Alzheimer Research Center, VU Medical Center

Amsterdam, 1081 HV, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 33974419 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

VX-745

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Results Point of Contact

• Title: John Alam
• Organization: EIP Pharma

jalam@eippharma.com

Study Officials

• Philip Scheltens, MD

  Alheimer Research Center, VU medisch centrum

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2015
• First Posted: April 22, 2015
• Study Start: April 1, 2015
• Primary Completion: July 1, 2016
• Study Completion: September 1, 2016
• Last Updated: June 14, 2019
• Results First Posted: June 14, 2019

Record last verified: 2018-01

Locations

NL (1)