Alzheimer's Disease, Mild Cognitive Impairment
Conditions
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.
Interventions
DRUGVX-745
Orally-Active Selective P45 MAP Kinase inhibitor
Sponsors
EIP Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Amyloid Plaque Burden by 11C-PiB PET | Baseline compared to following 12 weeks' dosing with VX-745 | Percent change in global cortical amyloid specific PET signal (BPND) |
| Number of 11C-PiB Responders | Day 84 | Number of patients meeting protocol pre-specified definition of response: \> 7% reduction in global cortical BPND |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Wechsler Memory Scale (WMS) Immediate Recall Composite | Baseline to Day 84 | 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 | Change from baseline to Day 84 | 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. |
Countries
Netherlands
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Neflamapimod (VX-745) Dose 1 Active Group 1: VX-745 40 mg twice daily
VX-745: Orally-Active Selective P45 MAP Kinase inhibitor | 9 |
| Neflamapimod (VX-745) Dose 2 Active Group 2: VX-745 125 mg twice daily
VX-745: Orally-Active Selective P45 MAP Kinase inhibitor | 7 |
| Total | 16 |
Baseline characteristics
| Characteristic | Neflamapimod (VX-745) Dose 1 | Neflamapimod (VX-745) Dose 2 | Total |
|---|---|---|---|
| Age, Continuous | 68 years | 65 years | 66.5 years |
| Region of Enrollment Netherlands | 9 participants | 7 participants | 16 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 6 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 7 |
| other Total, other adverse events | 6 / 9 | 3 / 7 |
| serious Total, serious adverse events | 0 / 9 | 0 / 7 |
Outcome results
Primary
Number of 11C-PiB Responders
Number of patients meeting protocol pre-specified definition of response: \> 7% reduction in global cortical BPND
Time frame: Day 84
Population: All patients with baseline and Day 84 11C-PiB scan. One patient in 40 mg dose group could not cooperate for Day 84 PET scan due to having developed MRI-induced panic attack.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Neflamapimod (VX-745) Dose 1 | Number of 11C-PiB Responders | 3 Participants |
| Neflamapimod (VX-745) Dose 2 | Number of 11C-PiB Responders | 1 Participants |
Primary
Percent Change From Baseline in Amyloid Plaque Burden by 11C-PiB PET
Percent change in global cortical amyloid specific PET signal (BPND)
Time frame: Baseline compared to following 12 weeks' dosing with VX-745
Population: All patients with baseline and Day 84 11C-PiB scan. One patient in 40 mg dose group could not cooperate for Day 84 PET scan due to having developed MRI-induced panic attack.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Neflamapimod (VX-745) Dose 1 | Percent Change From Baseline in Amyloid Plaque Burden by 11C-PiB PET | -4.57 percentage change from baseline |
| Neflamapimod (VX-745) Dose 2 | Percent Change From Baseline in Amyloid Plaque Burden by 11C-PiB PET | 4.57 percentage change from baseline |
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.
Time frame: Change from baseline to Day 84
Population: All patients with baseline and day 84 WMS testing data. One subject in 40 mg dose group did not complete the Day 84 WMS assessment after having developed MRI-induced panic attack.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neflamapimod (VX-745) Dose 1 | Wechsler Memory Scale (WMS) Delayed Recall Composite | 7.5 units on a scale | Standard Deviation 7 |
| Neflamapimod (VX-745) Dose 2 | Wechsler Memory Scale (WMS) Delayed Recall Composite | 10.4 units on a scale | Standard Deviation 11.9 |
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.
Time frame: Baseline to Day 84
Population: All patients with baseline and day 84 WMS testing data. One subject in 40 mg dose group did not complete the Day 84 WMS assessment after having developed MRI-induced panic attack.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Neflamapimod (VX-745) Dose 1 | Wechsler Memory Scale (WMS) Immediate Recall Composite | 7.0 units on a scale | Standard Deviation 11 |
| Neflamapimod (VX-745) Dose 2 | Wechsler Memory Scale (WMS) Immediate Recall Composite | 13.4 units on a scale | Standard Deviation 12.2 |