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

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ClinicalTrials.gov Identifier: NCT02423200
Recruitment Status : Completed
First Posted : April 22, 2015
Results First Posted : April 3, 2018
Last Update Posted : April 3, 2018
Sponsor:
Information provided by (Responsible Party):
EIP Pharma, LLC

Brief 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 VX-745 during dosing.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: VX-745 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Study Start Date : April 2015
Actual Primary Completion Date : September 2016
Actual Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: VX-745 dose level 1
Active Group 1: VX-745 dose level 1 twice daily
Drug: VX-745
Orally-active P38 MAP kinase alpha-selective inhibitor
Experimental: VX-745 dose level 2
Active Group 1: VX-745 dose level 2 twice daily
Drug: VX-745
Orally-active P38 MAP kinase alpha-selective inhibitor



Primary Outcome Measures :
  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 Outcome Measures :
  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.



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Ages Eligible for Study:   60 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02423200


Locations
United States, California
Parexel International
Glendale, California, United States, 91206
Sponsors and Collaborators
EIP Pharma, LLC
Investigators
Principal Investigator: Hakop Gevorkyan, MD Parexel

Responsible Party: EIP Pharma, LLC
ClinicalTrials.gov Identifier: NCT02423200     History of Changes
Other Study ID Numbers: EIP14-745-303
First Posted: April 22, 2015    Key Record Dates
Results First Posted: April 3, 2018
Last Update Posted: April 3, 2018
Last Verified: April 2018

Additional relevant MeSH terms:
Alzheimer Disease
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders