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

A Phase 2 study testing VX-745 in people with Alzheimer's Disease, run by EIP Pharma Inc at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This study will assess the effects of VX-745 on markers of disease in the central nervous system of patients with MCI due to AD or with mild AD. The study will also evaluate the safety and tolerability of VX-745 in these patients during 6 weeks of dosing, as well as the plasma and cerebrospinal fluid concentrations of… Read more about this study

Who is it for?: Ages 60 to 85 years
Conditions the study is for: Alzheimer's Disease
What is being tested?: VX-745
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 1 siteUnited States
Study dates: Apr 2015to Nov 2016
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 60 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age 60 - 85 (inclusive)
Willing and able to provide informed consent
Clinical presentation consistent with MCI due to AD or of mild AD
Gradual progressive decline in memory function over >6 months
Amnestic presentation on neuropsychological testing with rapid forgetting (% reduction 1.5 standard deviations below the mean)
Clinical Dementia Rating (CDR) Sum of Box (SOB) score ≥0.5

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Mini-Mental State Examination (MMSE) range: 20 to 30
Brain hypometabolism by 18F-2-fluoro-2-deoxyglucose (FDG)-PET
Participants may be taking medications for AD, provided that the dose of these medications has been stable for >3 months.

Who cannot join

Evidence of neurodegenerative disease other than AD
Inability for any reason to undergo MRI scans (e.g. pacemaker, vascular stent or stent graft). Patients who require sedation for screening procedures such as MRI may receive a short-acting sedative.
Psychiatric disorder that would compromise ability to comply with study requirements
History of cancer within the last 5 years, except basal cell carcinoma, non-squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over the past 2 years
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

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Psychotropic drugs taken within 1 month. Anticoagulant drugs taken within 1 week.
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
Donation of >500 mL of blood or blood products within 2 months
History of alcohol and/or illicit drug abuse within 6 months.
Infection with hepatitis A, B or C or HIV.
Any factor deemed by the investigator to be likely to interfere with study conduction

Trial locations and contacts

1 site in 1 country.

United States1 site

Parexel International
Glendale, California, 91206

Other trials in United States

About this study

Official title: A Randomized, Open-Label, Multiple Dose Clinical Pharmacology Study of Two Doses of a Selective p38 MAP Kinase Inhibitor, VX-745 in Patients With Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease (AD) or With Mild AD

Conditions: Alzheimer's Disease
Being tested: VX-745
Medical subject headings: Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

VX-745Drug
Orally-active P38 MAP kinase alpha-selective inhibitor

Study groups in NCT02423200
Study group	Role	What they receive
VX-745 dose level 1	Experimental	Active Group 1: VX-745 dose level 1 twice daily Receives: Drug: VX-745
VX-745 dose level 2	Experimental	Active Group 1: VX-745 dose level 2 twice daily Receives: Drug: VX-745

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent Change From Baseline to End of Treatment in Cerebrospinal Fluid Levels of Cytokines
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.
Measured: Baseline and Day 42 of dosing with VX-745

Secondary outcomes (3)

Severe or Serious Adverse Events
Number of patients with severe or serious adverse events
Measured: At baseline and at each study visit during (days 1, 7, 14, 21, 28, 35 and 42) and after (day 51) dosing
Maximal CSF VX-745 Concentration
Ratio fo CSF to plasma drug concentration at time matched time points. Samples taken
Measured: 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.
Episodic Memory Function
Total Recall in Hopkins Verbal Learning Test (HVLT). Range is 0-36, with increases in score indicating improvement in cognitive function.
Measured: Change from baseline to Day 42

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2015Nov 2016

First posted22 Apr 2015 (estimated)
Study startApr 2015
Primary completionSep 2016
Study completionNov 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02423200
Sponsor's protocol ID: EIP14-745-303
Status last verified: Apr 2018
First submitted: 3 Apr 2015
Last updated: 3 Apr 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 33974419

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 3 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Open-Label, Multiple Dose Clinical Pharmacology Study of Two Doses of a Selective p38 MAP Kinase Inhibitor, VX-745 in Patients With Mild Cognitive Impairment (MCI) Due to Alzheimer's Disease (AD) or With Mild AD
ClinicalTrials.gov ID: NCT02423200
Acronym / sponsor ID: EIP14-745-303
Conditions: Alzheimer's Disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 16 participants (actual)
Lead sponsor: EIP Pharma IncIndustry (pharma, biotech, devices)
Study start: Apr 2015
Primary completion: Sep 2016 (actual)
Study completion: Nov 2016 (actual)
First posted: 22 Apr 2015 (estimated)
Results: Posted 3 Apr 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
VX-745 dose level 1	Experimental	Drug: VX-745Active Group 1: VX-745 dose level 1 twice daily
VX-745 dose level 2	Experimental	Drug: VX-745Active Group 1: VX-745 dose level 2 twice daily

Who may qualify

Ages: 60 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

Age 60 - 85 (inclusive)
Willing and able to provide informed consent
Clinical presentation consistent with MCI due to AD or of mild AD
Brain hypometabolism by 18F-2-fluoro-2-deoxyglucose (FDG)-PET
Participants may be taking medications for AD, provided that the dose of these medications has been stable for >3 months.

Key exclusion criteria (15 listed)

Evidence of neurodegenerative disease other than AD
Inability for any reason to undergo MRI scans (e.g. pacemaker, vascular stent or stent graft). Patients who require sedation for screening procedures such as MRI may receive a short-acting sedative.
Psychiatric disorder that would compromise ability to comply with study requirements
History of cancer within the last 5 years, except basal cell carcinoma, non-squamous skin carcinoma, prostate cancer or carcinoma in situ with no significant progression over the past 2 years
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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
VX-745Orally-active P38 MAP kinase alpha-selective inhibitor	Drug	VX-745 dose level 1, VX-745 dose level 2

Primary outcome

Percent Change From Baseline to End of Treatment in Cerebrospinal Fluid Levels of Cytokines
Time frame: Baseline and Day 42 of dosing with VX-745
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.

3 secondary outcomes

Severe or Serious Adverse Events
Time frame: At baseline and at each study visit during (days 1, 7, 14, 21, 28, 35 and 42) and after (day 51) dosing
Maximal CSF VX-745 Concentration
Time frame: 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.
Episodic Memory Function
Time frame: Change from baseline to Day 42

Results and safety

Results posted to the registry on 3 Apr 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Neflamapimod (VX-745) Dose Level 1	8	7
Neflamapimod (VX-745) Dose Level 2	1	1

Primary outcome: Percent Change From Baseline to End of Treatment in Cerebrospinal Fluid Levels of Cytokines

Time frame: Baseline and Day 42 of dosing with VX-745. Mean (Standard Deviation). Unit: percentage of baseline at Day 42

Measure	Overall Study Population n = 7
Value	137 (115)

Population analysed: 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

3 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Overall Study Population	0 of 9 (0%)	9 of 9 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33974419Tormahlen 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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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Hakop Gevorkyan, MD principal investigator

Parexel

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing VX-745 in people with Alzheimer's Disease, run by EIP Pharma Inc at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 3 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline to End of Treatment in Cerebrospinal Fluid Levels of Cytokines (time frame: Baseline and Day 42 of dosing with VX-745). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02423200, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2018; AzTrials last refreshed its copy on 8 Nov 2026.