Trial Outcomes & Findings for Clinical Pharmacology of p38 MAP Kinase Inhibitor, VX-745, in Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD (NCT NCT02423200)

Results Overview

Cytokines: Of nine cytokines assessed, only CSF IL-8 quantifiable at all time points. And so, only IL-8 levels are being reported herein. The analysis was exploratory and no statistical analysis was performed.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

Baseline and Day 42 of dosing with VX-745

Results posted on

2018-04-03

Participant Flow

During the course of the study, and after one subject had been enrolled in the 125 mg dose group, FDA mandated the removal of the 125 mg dose group. As a result, the number subjects was revised downward to 9, 8 as planned in the 40 mg dose group and 1 in the 125 mg dose group.

Participant milestones

Participant milestones
Measure	Neflamapimod (VX-745) Dose Level 1 Active Group 1: VX-745 40 mg twice daily Neflamapimod (VX-745): Orally-active P38 MAP kinase alpha-selective inhibitor	Neflamapimod (VX-745) Dose Level 2 Active Group 1: VX-745 125 mg twice daily Neflamapimod (VX-745): Orally-active P38 MAP kinase alpha-selective inhibitor
Overall Study STARTED	8	1
Overall Study COMPLETED	7	1
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Clinical Pharmacology of p38 MAP Kinase Inhibitor, VX-745, in Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	VX-745 Dose Level 1 n=8 Participants Active Group 1: VX-745 dose level 1 twice daily VX-745: Orally-active P38 MAP kinase alpha-selective inhibitor	VX-745 Dose Level 2 n=1 Participants Active Group 1: VX-745 dose level 2 twice daily VX-745: Orally-active P38 MAP kinase alpha-selective inhibitor	Total n=9 Participants Total of all reporting groups
Age, Continuous	71 years n=5 Participants	68 years n=7 Participants	71 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	0 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	8 count of participants n=5 Participants	1 count of participants n=7 Participants	9 count of participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 42 of dosing with VX-745

Population: As there was only one subject in the 125 mg dose group (see Pre-Assignment Details), and the blood concentration levels in this subject was similar to that in 125 mg dose group, this subjects data was combined with the 40 mg dose group in this analysis. In addition, two subjects did not have Day 42 CSF samples available for analysis

Cytokines: Of nine cytokines assessed, only CSF IL-8 quantifiable at all time points. And so, only IL-8 levels are being reported herein. The analysis was exploratory and no statistical analysis was performed.

Outcome measures

Outcome measures
Measure	Overall Study Population n=7 Participants Combined 40 mg and 125 mg subjects; N=7 with baseline and Day 42 results	Neflamapimod (VX-745) Dose Level 2 Active Group 1: VX-745 125 mg twice daily Neflamapimod (VX-745): Orally-active P38 MAP kinase alpha-selective inhibitor
Percent Change From Baseline to End of Treatment in Cerebrospinal Fluid Levels of Cytokines	137 percentage of baseline at Day 42 Standard Deviation 115	—

SECONDARY outcome

Timeframe: At baseline and at each study visit during (days 1, 7, 14, 21, 28, 35 and 42) and after (day 51) dosing

Number of patients with severe or serious adverse events

Outcome measures

Outcome measures
Measure	Overall Study Population n=8 Participants Combined 40 mg and 125 mg subjects; N=7 with baseline and Day 42 results	Neflamapimod (VX-745) Dose Level 2 n=1 Participants Active Group 1: VX-745 125 mg twice daily Neflamapimod (VX-745): Orally-active P38 MAP kinase alpha-selective inhibitor
Severe or Serious Adverse Events	0 Participants	0 Participants

SECONDARY outcome

Timeframe: All samples with quantifiable CSF drug levels were included (n=12). Eight were obtained 3-hours post-dose, either on Day 1 (n=4) or Day 42 (n=4). 3 samples were at 6-hours post-dose on Day 42; and one was at 6-hours post-dose on Day 1.

Population: As there was only one subject in the 125 mg dose group (see Pre-Assignment Details), and the blood concentration levels in this subject was similar to that in 125 mg dose group, this subjects data was combined with the 40 mg dose group in this analysis.

Ratio fo CSF to plasma drug concentration at time matched time points. Samples taken

Outcome measures

Outcome measures
Measure	Overall Study Population n=9 Participants Combined 40 mg and 125 mg subjects; N=7 with baseline and Day 42 results	Neflamapimod (VX-745) Dose Level 2 Active Group 1: VX-745 125 mg twice daily Neflamapimod (VX-745): Orally-active P38 MAP kinase alpha-selective inhibitor
Maximal CSF VX-745 Concentration	0.062 ratio of plasma drug concentration Standard Deviation 0.01	—

SECONDARY outcome

Timeframe: Change from baseline to Day 42

Population: As there was only one subject in the 125 mg dose group (see Pre-Assignment Details), and the blood concentration levels in this subject was similar to that in 125 mg dose group, this subjects data was combined with the 40 mg dose group in all outcome measure analyses. In addition, one subject did not have a Day 42 HVLT-R analysis.

Total Recall in Hopkins Verbal Learning Test (HVLT). Range is 0-36, with increases in score indicating improvement in cognitive function.

Outcome measures

Outcome measures
Measure	Overall Study Population n=8 Participants Combined 40 mg and 125 mg subjects; N=7 with baseline and Day 42 results	Neflamapimod (VX-745) Dose Level 2 Active Group 1: VX-745 125 mg twice daily Neflamapimod (VX-745): Orally-active P38 MAP kinase alpha-selective inhibitor
Episodic Memory Function	3.5 points on HLVT Total Recall (range 0-36) Standard Deviation 3.6	—

Adverse Events

Overall Study Population

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Overall Study Population n=9 participants at risk Combined 40 mg and 125 mg subjects. As there was only one subject in the 125 mg dose group (see Pre-Assignment Details), and the blood concentration levels in this subject was similar to that in 125 mg dose group, this subjects data was combined with the 40 mg dose group in the adverse event analysis.
Nervous system disorders Dizziness	22.2% 2/9 • Number of events 2
Nervous system disorders Headache	22.2% 2/9 • Number of events 2
Nervous system disorders Somnolence	22.2% 2/9 • Number of events 2
Vascular disorders Orthostatic hypotension	11.1% 1/9 • Number of events 1
Gastrointestinal disorders Diarrhea	11.1% 1/9 • Number of events 1
Gastrointestinal disorders Vomiting	11.1% 1/9 • Number of events 1
Vascular disorders Hot flush	11.1% 1/9 • Number of events 1

Additional Information

John Alam

EIP Pharma

Phone: 617-945-0794

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Clinical study was conducted at at clinical pharmacology unit owned by a contract research organization (CRO; Parexel) that was contracted by the sponsor to conduct the study. Site principal investigator is an employee of a contract research organization. As per the contract, the sponsor has "all rights, title and interest in the results".
Publication restrictions are in place

Restriction type: OTHER