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

Primary Purpose

Alzheimer's Disease, Mild Cognitive Impairment

Status

Completed

Phase

Phase 2

Locations

Netherlands

Study Type

Interventional

Intervention

VX-745

About this trial

This is an interventional treatment trial for Alzheimer's Disease

Eligibility Criteria

60 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Alzheimer Research Center, VU Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

VX-745 dose 1

VX-745 dose 2

Arm Description

Active Group 1: VX-745 40 mg twice daily

Active Group 2: VX-745 125 mg twice daily

Outcomes

Primary Outcome Measures

Percent Change From Baseline in Amyloid Plaque Burden by 11C-PiB PET

Percent change in global cortical amyloid specific PET signal (BPND)

Number of 11C-PiB Responders

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

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT02423122

First Posted

April 14, 2015

Last Updated

March 13, 2019

Sponsor

EIP Pharma Inc

1. Study Identification

Unique Protocol Identification Number

NCT02423122

Brief Title

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

2. Study Status

Record Verification Date

January 2018

Overall Recruitment Status

Completed

Study Start Date

April 2015 (undefined)

Primary Completion Date

July 2016 (Actual)

Study Completion Date

September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

EIP Pharma Inc

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer's Disease, Mild Cognitive Impairment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

16 (Actual)

8. Arms, Groups, and Interventions

Arm Title

VX-745 dose 1

Arm Type

Experimental

Arm Description

Active Group 1: VX-745 40 mg twice daily

Arm Title

VX-745 dose 2

Arm Type

Experimental

Arm Description

Active Group 2: VX-745 125 mg twice daily

Intervention Type

Drug

Intervention Name(s)

VX-745

Intervention Description

Orally-Active Selective P45 MAP Kinase inhibitor

Primary Outcome Measure Information:

Title

Percent Change From Baseline in Amyloid Plaque Burden by 11C-PiB PET

Description

Percent change in global cortical amyloid specific PET signal (BPND)

Time Frame

Baseline compared to following 12 weeks' dosing with VX-745

Title

Number of 11C-PiB Responders

Description

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

Time Frame

Day 84

Secondary Outcome Measure Information:

Title

Wechsler Memory Scale (WMS) Immediate Recall Composite

Description

Time Frame

Baseline to Day 84

Title

Wechsler Memory Scale (WMS) Delayed Recall Composite

Description

Time Frame

Change from baseline to Day 84

10. Eligibility

Sex

All

Minimum Age & Unit of Time

60 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Philip Scheltens, MD

Organizational Affiliation

Alheimer Research Center, VU medisch centrum

Official's Role

Principal Investigator

Facility Information:

Facility Name

Alzheimer Research Center, VU Medical Center

City

Amsterdam

ZIP/Postal Code

1081 HV

Country

Netherlands

12. IPD Sharing Statement

Citations:

PubMed Identifier

33974419

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.

Results Reference

derived

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

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