Skip to main content
OpenTrials
Completed

NCT Number: NCT02423200

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

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 VX-745 during dosing.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Alzheimer's Disease Alzheimer Disease Brain Diseases Central Nervous System Diseases Dementia Mental Disorders Nervous System Diseases Neurocognitive Disorders Neurodegenerative Diseases Tauopathies

Age range

60 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Parexel International

Glendale, California, 91206, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • 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.

Exclusion criteria

  • 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
  • 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

Treatment and study plan

VX-745

Drug

Orally-active P38 MAP kinase alpha-selective inhibitor

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

    Number of patients with severe or serious adverse events

  2. 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.

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

  3. Episodic Memory Function

    Time frame: Change from baseline to Day 42

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

Sponsors and collaborators

Lead sponsor

EIP Pharma Inc

Industry

Registry information

Official study 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

Important dates

Study start
2015
Primary completion
2016
Study completion
2016
First posted
Apr 22, 2015
Registry last updated
Apr 3, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.