Clinical Pharmacology of p38 MAP Kinase Inhibitor, VX-745, in Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD
This trial is active, not recruiting.
|Sponsor||EIP Pharma, LLC|
|Start date||April 2015|
|End date||September 2016|
|Trial size||16 participants|
|Trial identifier||NCT02423200, EIP14-745-303|
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.
|Endpoint classification||safety/efficacy study|
|Intervention model||parallel assignment|
|Masking||double blind (subject, caregiver, investigator, outcomes assessor)|
Percent change from Baseline to end of treatment in cerebrospinal fluid levels of cytokines, amyloid-beta, phospho-tau, neurofilament light chain and butylcholinesterase and fludeoxyglucose positron emission tomography
time frame: Baseline and days 1 and 42 of dosing with VX-745
Number and severity of adverse events with VX-745 in patients with MCI or AD
time frame: At baseline and at each study visit during (days 1, 7, 14, 21, 28, 35 and 42) and after (day 51) dosing
Area-under-curve (AUC) of plasma drug concentrations of VX-745
time frame: On day 1 and 42 of VX-745 dosing, at 0.5, 1, 2, 3, 4, 5, 6 and 8 hours post-dose
Maximal CSF VX-745 concentration
time frame: On day 1 and 42 of VX-745 dosing, 0, 3 and 6h post-dose
Male or female participants from 60 years up to 85 years old.
- 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.
- 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
|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|
|Principal investigator||Hakop Gevorkyan, MD|
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