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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| VX-745 dose 1 | Experimental | Active Group 1: VX-745 40 mg twice daily |
|
| VX-745 dose 2 | Experimental | Active Group 2: VX-745 125 mg twice daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VX-745 | Drug | Orally-Active Selective P45 MAP Kinase inhibitor |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Philip Scheltens, MD | Alheimer Research Center, VU medisch centrum | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Alzheimer Research Center, VU Medical Center | Amsterdam | 1081 HV | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33974419 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Neflamapimod (VX-745) Dose 1 | Active Group 1: VX-745 40 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor |
| FG001 | Neflamapimod (VX-745) Dose 2 | Active Group 2: VX-745 125 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Neflamapimod (VX-745) Dose 1 | Active Group 1: VX-745 40 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor |
| BG001 | Neflamapimod (VX-745) Dose 2 | Active Group 2: VX-745 125 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change From Baseline in Amyloid Plaque Burden by 11C-PiB PET | Percent change in global cortical amyloid specific PET signal (BPND) | 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. | Posted | Median | Inter-Quartile Range | percentage change from baseline | Baseline compared to following 12 weeks' dosing with VX-745 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 40 mg Dose Group | 0 | 9 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John Alam | EIP Pharma | jalam@eippharma.com |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| C464966 | VX-745 |
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| 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 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Primary | Number of 11C-PiB Responders | Number of patients meeting protocol pre-specified definition of response: > 7% reduction in global cortical BPND | 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. | Posted | Count of Participants | Participants | 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | 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. | 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. | Posted | Mean | Standard Deviation | units on a scale | Change from baseline to Day 84 |
|
|
|
| 0 |
| 9 |
| 6 |
| 9 |
| EG001 | 125 mg Dose Group | 0 | 7 | 0 | 7 | 3 | 7 |
| Somnolence | Nervous system disorders | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | Non-systematic Assessment |
|
| Influenza like illness | General disorders | Non-systematic Assessment |
|
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| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |