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

NCT03435861 | Completed Phase 2

• 1 other identifier: RC31/16/8371
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (3)

• 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

  3 month

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

  SUVs in the five lobes will be calculated.

  3 month

• 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.

  3 month

Secondary Outcomes (35)

• Neuropsychological assessment to assess the following cognitive functions 1:

  3 month

• Neuropsychological assessment to assess the following cognitive functions 2:

  3 month

• Neuropsychological assessment to assess the following cognitive functions 1.1:

  3 month

• Neuropsychological assessment to assess the following cognitive functions 2.2:

  3 month

• Neuropsychological assessment to assess the following cognitive functions 3:

  3 month

Study Arms (2)

VX-745

EXPERIMENTAL

In 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

Drug: VX-745

placebo

PLACEBO COMPARATOR

In the present study, placebo will be given twice a day (1 tab. , twice), orally for 12 weeks

Drug: placebo

Interventions

VX-745 DRUG

active drug capsules

Also known as: neflamapimod

VX-745

placebo DRUG

placebo capsules

placebo

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• University Hospital, Toulouse: lead
• Fondation Plan Alzheimer: collaborator

Study Sites (1)

CHU Toulouse

Toulouse, 31000, France

Location

Related Publications (1)

• 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.

  PMID: 33974419 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Interventions

VX-745

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Jeremie PARIENTE, MD

  University Hospital, Toulouse

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: December 22, 2017
• First Posted: February 19, 2018
• Study Start: October 8, 2018
• Primary Completion: April 30, 2021
• Study Completion: June 30, 2021
• Last Updated: June 22, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)