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Alzheimer DiseasePhase 2VIPNCT03435861

Effect of Neflamapimod on Brain Inflammation in Alzheimer's Disease Patients

A Phase 2 study testing VX-745 in people with Alzheimer Disease, run by University Hospital, Toulouse at 1 site in France.

Completed

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

Official record
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Trial summary

For this project, neflamapimod and placebo will be provided free of charge by the EIP company (www.eippharma.com). Neflamapimod is currently tested in 2 clinical trials in AD, one in Europe (The Netherlands) and one in the USA (clinical trials.gov/VX-745). Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Alzheimer Disease
What is being tested?
VX-745
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
34 participants
Where
1 siteFrance
Study dates
8 Oct 2018to 30 Jun 2021
Phase
Phase 2
Are there results?
None posted in the registry

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 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • A group of 40 AD patients at an early stage (prodromal) will be recruited. Patient's recruitment will follow the most recent research criteria for AD in its "typical form" (Dubois, Feldman et al. 2014):
  • Age 50 - 90 (inclusive)
  • Willing and able to provide informed consent
  • Objective memory impairment corroborated by level of performance on a standardized memory test (Free and Cued Selective Reminding test, (Grober, Hall et al. 2008)) < -1.5 DS according to established norms and
  • Documented cerebral amyloidopathy using CSF analysis or PET amyloid imaging and
  • Early stage of the disease (Mini Mental State Examination > 20) (Folstein, Robins et al. 1983).

Who cannot join

  • • Evidence of neurodegenerative disease other than AD
  • Inability for any reason to undergo MRI scans (e.g. pacemaker). 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 (<60 days) changes to AD medications prescribed for cognitive reasons or with the potential to impact cognition
Show all 14Show fewer
  • 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
  • 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.

France1 site

  • CHU Toulouse

    Toulouse, 31000

Other trials in France

About this study

Official title: Effect of Neflamapimod (VX-745) on Brain Inflammation Using Positron Emission Tomography (PET) Scan in Alzheimer's Disease (AD) Patients

For this project, neflamapimod and placebo will be provided free of charge by the EIP company (www.eippharma.com). Neflamapimod is currently tested in 2 clinical trials in AD, one in Europe (The Netherlands) and one in the USA (clinical trials.gov/VX-745). The company commenced in May 2015 dosing in two phase 2a clinical studies in patients with Early AD: one in the Netherlands that is focused on PET amyloid imaging as the primary biomarker of drug effect, and one in the US (California) that is focused on Cerebrospinal fluid (CSF) evaluation to determine CSF drug concentrations and effects on inflammatory markers and disease biomarkers. Pharmacokinetic evaluation in these patients has demonstrated blood drug concentration levels in the predicted therapeutic range; and importantly, the data from the US study demonstrate that the drug achieves target drug concentrations in CSF, thus confirming the drug robustly enters the brain in humans.

The present project offers us a unique chance to test this promising drug in AD patients. The aim of the study is to focus on PET neuroinflammation imaging as the primary biomarker of this drug effect. The chosen biomarker for imaging neuroinflammation in patients is [1 8F]-DPA714.

Read the detailed description

The present project is an intervention proof of concept study to test the efficacy of neflamapimod in a population of AD patients at an early stage.

To track the impact of this drug in patients, the investigators will use an innovative radiotracer, [18F]DPA-714, as a promising ligand of microglial activation targeting the translocator protein (TSPO), specific of microglial activation. The use of [18F]DPA-714 will allow to monitor the evolution of neuroinflammation in patients as a function of treatment. The main objective will be to compare the level of inflammation using the [18F]DPA-714 in neflamapimod and placebo groups after 12 weeks of treatment. Blood and cerebrospinal fluid (CSF) samples and magnetic resonance imaging (MRI) will also be collected to assess inflammation markers and brain structure respectively in these patients.

Being tested
VX-745, placebo
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

    Also called neflamapimod

    active drug capsules

  • placeboDrug

    placebo capsules

Study groups in NCT03435861
Study groupRoleWhat they receive
VX-745ExperimentalIn the present study, VX-745 will be given at the dosage of 40 mg twice a day (1 tab. of 40 mg, twice), orally for 12 weeks
Receives: Drug: VX-745
placeboPlacebo comparatorIn the present study, placebo will be given twice a day (1 tab. , twice), orally for 12 weeks
Receives: Drug: placebo

What is being measured

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

  1. brain inflammation assessed by [18F]-DPA714, Standard Uptake Value (SUV)

    To track the impact of this drug in patients, investigators will use an innovative radiotracer, [18F]DPA-714, as a promising ligand of microglial activation targeting the translocator protein (TSPO), specific of microglial activation. The use of [18F]DPA-714 will allow us to monitor the evolution of neuroinflammation in patients as a function of treatment. the main objective will be to compare the level of inflammation using the [18F]DPA-714 in neflamapimod and placebo.

    Regional cortical DPA-714 mean SUV will be measured in each subject using a Matlab (The MathWorks®) script. Mean global SUVs will be calculated

    Measured: 3 month

  2. brain inflammation assessed by [18F]-DPA714, Standard Uptake Value (SUV) 2

    SUVs in the five lobes will be calculated.

    Measured: 3 month

  3. brain inflammation assessed by [18F]-DPA714, Standard Uptake Value (SUV)3

    SUVs in specific regions of interest (ROIs: orbitofrontal, anterior cingulate, posterior cingulate and precuneus) will be calculated.

    Measured: 3 month

Secondary outcomes (35)

  1. Neuropsychological assessment to assess the following cognitive functions 1:

    Memory: Rey Figure

    Measured: 3 month

  2. Neuropsychological assessment to assess the following cognitive functions 2:

    Memory: DMS 48,

    Measured: 3 month

  3. Neuropsychological assessment to assess the following cognitive functions 1.1:

    Language: confrontation naming (Gremots),

    Measured: 3 month

  4. Neuropsychological assessment to assess the following cognitive functions 2.2:

    Language: FAS fluencies,

    Measured: 3 month

  5. Neuropsychological assessment to assess the following cognitive functions 3:

    • Attention and executive functions: D2

    Measured: 3 month

  6. Neuropsychological assessment to assess the following cognitive functions 4:

    • Attention and executive functions: TEA

    Measured: 3 month

  7. Neuropsychological assessment to assess the following cognitive functions 5:

    • Attention and executive functions: SDMT WAIS

    Measured: 3 month

  8. Blood and CSF biomarkers of inflammation1

    ApoE phenotype

    Measured: 3 month

  9. Blood and CSF biomarkers of inflammation 2

    TSPO phenotype,

    Measured: 3 month

  10. Blood and CSF biomarkers of inflammation 3

    TNFa,

    Measured: 3 month

  11. Blood and CSF biomarkers of inflammation 4

    IL-1b,

    Measured: 3 month

  12. Blood and CSF biomarkers of inflammation 5

    IFNg

    Measured: 3 month

  13. Blood and CSF biomarkers of inflammation 6

    IL-12

    Measured: 3 month

  14. Blood and CSF biomarkers of inflammation 7

    IFNa/b

    Measured: 3 month

  15. Blood and CSF biomarkers of inflammation 8

    IL-10

    Measured: 3 month

  16. Blood and CSF biomarkers of inflammation 9

    IL-6

    Measured: 3 month

  17. Blood and CSF biomarkers of inflammation 10

    IL-8,

    Measured: 3 month

  18. Blood and CSF biomarkers of inflammation 11

    MCP-1,

    Measured: 3 month

  19. Blood and CSF biomarkers of inflammation 12

    GM-CSF

    Measured: 3 month

  20. Blood and CSF biomarkers of inflammation 13

    IL-27

    Measured: 3 month

  21. Blood and CSF biomarkers of inflammation 14

    chimiokines receptors,

    Measured: 3 month

  22. Blood and CSF biomarkers of inflammation 15

    PD-1,

    Measured: 3 month

  23. Blood and CSF biomarkers of inflammation 16

    CD14/16

    Measured: 3 month

  24. Blood and CSF biomarkers of inflammation 17

    p-tau,

    Measured: 3 month

  25. Blood and CSF biomarkers of inflammation 18

    abéta42,

    Measured: 3 month

  26. Blood and CSF biomarkers of inflammation 19

    Abeta40,

    Measured: 3 month

  27. Blood and CSF biomarkers of inflammation 20

    cells count

    Measured: 3 month

  28. Blood and CSF biomarkers of inflammation 21

    TNFa

    Measured: 3 month

  29. Blood and CSF biomarkers of inflammation 22

    IL-1b

    Measured: 3 month

  30. Blood and CSF biomarkers of inflammation 23

    IL-12

    Measured: 3 month

  31. Blood and CSF biomarkers of inflammation 24

    MCP-1

    Measured: 3 month

  32. Blood and CSF biomarkers of inflammation 25

    GM-CSF

    Measured: 3 month

  33. Blood and CSF biomarkers of inflammation 26

    IL-27,

    Measured: 3 month

  34. Blood and CSF biomarkers of inflammation 27

    PD-1

    Measured: 3 month

  35. Blood and CSF biomarkers of inflammation 28

    CD14/16

    Measured: 3 month

Timeline

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

  1. First posted19 Feb 2018
  2. Study start8 Oct 2018
  3. Primary completion30 Apr 2021
  4. Study completion30 Jun 2021

Resources

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
Model description
Our mono-centric project will consist in a double-blinded randomized placebo-controlled study, assessing the effect of neflamapimod on brain inflammation in patients suffering of AD by using \[18F\]-DPA714
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03435861
Sponsor's protocol ID
RC31/16/8371
Acronym
VIP
Status last verified
Jun 2023
First submitted
22 Dec 2017
Last updated
22 Jun 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Gouilly D, Da-Costa A, Vrillon A, Pistono A, Goubeaud M, Bertrand E, Germain J, Ainaoui N, Bras S, Catala H, Planton M, Lemesle B, Hitzel A, Salabert AS, Nogueira L, Mouton-Liger F, Meligne D, Jasse L, Rafiq M, Sarton B, Silva S, Alam J, Paquet C, Tauber C, Thalamas C, Payoux P, Peran P, Pariente J. Inhibition of p38alpha MAPK increases short-term astrocyte reactivity: the exploratory VIP trial in early Alzheimer's disease. J Neuroinflammation. 2025 Nov 24;22(1):298. doi: 10.1186/s12974-025-03625-x.

    PubMed 41287056

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing VX-745 in people with Alzheimer Disease, run by University Hospital, Toulouse at 1 site in France.

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 6 inclusion and 14 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 22 Jun 2023. 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 France. 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. Some participants in this study may receive a placebo. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

brain inflammation assessed by [18F]-DPA714, Standard Uptake Value (SUV) (time frame: 3 month). The study lists 3 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 NCT03435861, 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 22 Jun 2023.

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