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

NCT02423200 | Completed Phase 2 Results

• 1 other identifier: EIP14-745-303
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer's Disease

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline to End of Treatment in Cerebrospinal Fluid Levels of Cytokines

  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.

  Baseline and Day 42 of dosing with VX-745

Secondary Outcomes (3)

• Severe or Serious Adverse Events

  At baseline and at each study visit during (days 1, 7, 14, 21, 28, 35 and 42) and after (day 51) dosing

• Maximal CSF VX-745 Concentration

  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.

• Episodic Memory Function

  Change from baseline to Day 42

Study Arms (2)

VX-745 dose level 1

EXPERIMENTAL

Active Group 1: VX-745 dose level 1 twice daily

Drug: VX-745

VX-745 dose level 2

EXPERIMENTAL

Active Group 1: VX-745 dose level 2 twice daily

Drug: VX-745

Interventions

VX-745 DRUG

Orally-active P38 MAP kinase alpha-selective inhibitor

VX-745 dose level 1; VX-745 dose level 2

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• EIP Pharma Inc: lead

Study Sites (1)

Parexel International

Glendale, California, 91206, United States

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

Results Point of Contact

• Title: John Alam
• Organization: EIP Pharma

jalam@eippharma.com

617-945-0794

Study Officials

• Hakop Gevorkyan, MD

  Parexel

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2015
• First Posted: April 22, 2015
• Study Start: April 1, 2015
• Primary Completion: September 1, 2016
• Study Completion: November 1, 2016
• Last Updated: April 3, 2018
• Results First Posted: April 3, 2018

Record last verified: 2018-04

Locations

US (1)