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

NCT ID: NCT02423200

Last Updated: 2018-04-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2016-11-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

VX-745 dose level 1

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

Group Type: EXPERIMENTAL

VX-745

Intervention Type: DRUG

Orally-active P38 MAP kinase alpha-selective inhibitor

VX-745 dose level 2

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

Group Type: EXPERIMENTAL

VX-745

Intervention Type: DRUG

Orally-active P38 MAP kinase alpha-selective inhibitor

Interventions

VX-745

Orally-active P38 MAP kinase alpha-selective inhibitor

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

EIP Pharma Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hakop Gevorkyan, MD

Role: PRINCIPAL_INVESTIGATOR

Parexel

Locations

Parexel International

Glendale, California, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33974419 (View on PubMed)

Other Identifiers

EIP14-745-303

Identifier Type: -

Identifier Source: org_study_id