Trial Outcomes & Findings for A PET Study of the Effects of p38 MAP Kinase Inhibitor, VX-745, on Amyloid Plaque Load in Alzheimer's Disease (AD) (NCT NCT02423122)

NCT ID: NCT02423122

Last Updated: 2019-06-14

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

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

Results posted on

2019-06-14

Participant Flow

Participant milestones

Participant milestones
Measure
Neflamapimod (VX-745) Dose 1
Active Group 1: VX-745 40 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor
Neflamapimod (VX-745) Dose 2
Active Group 2: VX-745 125 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor
Overall Study
STARTED
9
7
Overall Study
COMPLETED
9
7
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Neflamapimod (VX-745) Dose 1
n=9 Participants
Active Group 1: VX-745 40 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor
Neflamapimod (VX-745) Dose 2
n=7 Participants
Active Group 2: VX-745 125 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor
Total
n=16 Participants
Total of all reporting groups
Age, Continuous
68 years
n=5 Participants
65 years
n=7 Participants
66.5 years
n=5 Participants
Sex: Female, Male
Female
2 Participants
n=5 Participants
4 Participants
n=7 Participants
6 Participants
n=5 Participants
Sex: Female, Male
Male
7 Participants
n=5 Participants
3 Participants
n=7 Participants
10 Participants
n=5 Participants
Region of Enrollment
Netherlands
9 participants
n=5 Participants
7 participants
n=7 Participants
16 participants
n=5 Participants

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure
Neflamapimod (VX-745) Dose 1
n=8 Participants
Active Group 1: VX-745 40 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor
Neflamapimod (VX-745) Dose 2
n=7 Participants
Active Group 2: VX-745 125 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor
Percent Change From Baseline in Amyloid Plaque Burden by 11C-PiB PET
-4.57 percentage change from baseline
Interval -11.65 to 4.83
4.57 percentage change from baseline
Interval 0.56 to 12.25

PRIMARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure
Neflamapimod (VX-745) Dose 1
n=8 Participants
Active Group 1: VX-745 40 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor
Neflamapimod (VX-745) Dose 2
n=7 Participants
Active Group 2: VX-745 125 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor
Number of 11C-PiB Responders
3 Participants
1 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Neflamapimod (VX-745) Dose 1
n=8 Participants
Active Group 1: VX-745 40 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor
Neflamapimod (VX-745) Dose 2
n=7 Participants
Active Group 2: VX-745 125 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor
Wechsler Memory Scale (WMS) Immediate Recall Composite
7.0 units on a scale
Standard Deviation 11.0
13.4 units on a scale
Standard Deviation 12.2

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure
Neflamapimod (VX-745) Dose 1
n=8 Participants
Active Group 1: VX-745 40 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor
Neflamapimod (VX-745) Dose 2
n=7 Participants
Active Group 2: VX-745 125 mg twice daily VX-745: Orally-Active Selective P45 MAP Kinase inhibitor
Wechsler Memory Scale (WMS) Delayed Recall Composite
7.5 units on a scale
Standard Deviation 7.0
10.4 units on a scale
Standard Deviation 11.9

Adverse Events

40 mg Dose Group

Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths

125 mg Dose Group

Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
40 mg Dose Group
n=9 participants at risk
125 mg Dose Group
n=7 participants at risk
Gastrointestinal disorders
Diarrhea
33.3%
3/9 • Number of events 3
0.00%
0/7
Nervous system disorders
Somnolence
11.1%
1/9 • Number of events 1
14.3%
1/7 • Number of events 1
Gastrointestinal disorders
Abdominal pain
11.1%
1/9 • Number of events 1
14.3%
1/7 • Number of events 1
General disorders
Influenza like illness
11.1%
1/9 • Number of events 1
14.3%
1/7 • Number of events 1

Additional Information

John Alam

EIP Pharma

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place

Restriction type: LTE60