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

NCT ID: NCT02423122

Last Updated: 2019-06-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2016-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

VX-745 dose 1

Active Group 1: VX-745 40 mg twice daily

Group Type: EXPERIMENTAL

VX-745

Intervention Type: DRUG

Orally-Active Selective P45 MAP Kinase inhibitor

VX-745 dose 2

Active Group 2: VX-745 125 mg twice daily

Group Type: EXPERIMENTAL

VX-745

Intervention Type: DRUG

Orally-Active Selective P45 MAP Kinase inhibitor

Interventions

VX-745

Orally-Active Selective P45 MAP Kinase inhibitor

Intervention Type: DRUG

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

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EIP Pharma Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philip Scheltens, MD

Role: PRINCIPAL_INVESTIGATOR

Alheimer Research Center, VU medisch centrum

Locations

Alzheimer Research Center, VU Medical Center

Amsterdam, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 33974419 (View on PubMed)

Other Identifiers

EIP-VX00-745-302

Identifier Type: -

Identifier Source: org_study_id