Alzheimer's DiseasePhase 2NCT02423122
A PET Study of the Effects of p38 MAP Kinase Inhibitor, VX-745, on Amyloid Plaque Load in Alzheimer's Disease (AD)
A Phase 2 study testing VX-745 in people with Alzheimer's Disease and Mild Cognitive Impairment, run by EIP Pharma Inc at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 to 85 years
- Conditions the study is for
- Alzheimer's Disease, Mild Cognitive Impairment
- 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 siteNetherlands
- Study dates
- Apr 2015to Sep 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
- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Alzheimer Research Center, VU Medical Center
Amsterdam, 1081 HV
About this study
Official title: A Clinical Study of Two Doses of a Selective p38 MAP Kinase Inhibitor, VX-745, to Evaluate the Effects of 12-Week Oral Twice-Daily Dosing on Amyloid Plaque Load as Assessed by Quantitative Dynamic 11C-PiB Positive Emission Tomography (PET) Amyloid Scanning
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.
- Conditions
- Alzheimer's Disease, Mild Cognitive Impairment
- Being tested
- VX-745
- Medical subject headings
- Alzheimer Disease, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VX-745Drug
Orally-Active Selective P45 MAP Kinase inhibitor
| Study group | Role | What they receive |
|---|---|---|
| VX-745 dose 1 | Experimental | Active Group 1: VX-745 40 mg twice daily Receives: Drug: VX-745 |
| VX-745 dose 2 | Experimental | Active Group 2: VX-745 125 mg 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 in Amyloid Plaque Burden by 11C-PiB PET
Percent change in global cortical amyloid specific PET signal (BPND)
Measured: 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
Measured: Day 84
Secondary outcomes (2)
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.
Measured: Baseline to Day 84
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.
Measured: Change from baseline to Day 84
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2015 (estimated)
- Study startApr 2015
- Primary completionJul 2016
- Study completionSep 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 (2)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)
Sponsor and investigators
- Lead sponsor
- EIP Pharma Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Philip Scheltens, MD, Principal investigator, Alheimer Research Center, VU medisch centrum
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02423122
- Sponsor's protocol ID
- EIP-VX00-745-302
- Status last verified
- Jan 2018
- First submitted
- 14 Apr 2015
- Last updated
- 14 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Prins ND, de Haan W, Gardner A, Blackburn K, Chu HM, Galvin JE, Alam JJ. Phase 2A Learnings Incorporated into RewinD-LB, a Phase 2B Clinical Trial of Neflamapimod in Dementia with Lewy Bodies. J Prev Alzheimers Dis. 2024;11(3):549-557. doi: 10.14283/jpad.2024.36.
PubMed 38706271Tormahlen 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
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Study of Two Doses of a Selective p38 MAP Kinase Inhibitor, VX-745, to Evaluate the Effects of 12-Week Oral Twice-Daily Dosing on Amyloid Plaque Load as Assessed by Quantitative Dynamic 11C-PiB Positive Emission Tomography (PET) Amyloid Scanning
- ClinicalTrials.gov ID
- NCT02423122
- Acronym / sponsor ID
- EIP-VX00-745-302
- Conditions
- Alzheimer's Disease, Mild Cognitive Impairment
- 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
- Jul 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 22 Apr 2015 (estimated)
- Results
- Posted 14 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 1 | Experimental | Drug: VX-745Active Group 1: VX-745 40 mg twice daily |
| VX-745 dose 2 | Experimental | Drug: VX-745Active Group 2: VX-745 125 mg twice daily |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (10 listed)
- 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
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 Selective P45 MAP Kinase inhibitor | Drug | VX-745 dose 1, VX-745 dose 2 |
Primary outcome
Percent Change From Baseline in Amyloid Plaque Burden by 11C-PiB PET
Time frame: 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
Time frame: Day 84
Number of patients meeting protocol pre-specified definition of response: > 7% reduction in global cortical BPND
2 secondary outcomes
Wechsler Memory Scale (WMS) Immediate Recall Composite
Time frame: Baseline to Day 84
Wechsler Memory Scale (WMS) Delayed Recall Composite
Time frame: Change from baseline to Day 84
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38706271Prins ND, de Haan W, Gardner A, Blackburn K, Chu HM, Galvin JE, Alam JJ. Phase 2A Learnings Incorporated into RewinD-LB, a Phase 2B Clinical Trial of Neflamapimod in Dementia with Lewy Bodies. J Prev Alzheimers Dis. 2024;11(3):549-557. doi: 10.14283/jpad.2024.36.
- 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.
Philip Scheltens, MD principal investigator
Alheimer Research Center, VU medisch centrum
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 and Mild Cognitive Impairment, run by EIP Pharma Inc at 1 site in Netherlands.
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 7 inclusion and 10 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 14 Jun 2019. 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 Netherlands. 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 14 Jun 2019). 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 in Amyloid Plaque Burden by 11C-PiB PET (time frame: Baseline compared to following 12 weeks' dosing with VX-745). The study lists 2 primary outcomes in all. 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 NCT02423122, which also lists 2 linked publications.
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 14 Jun 2019.