R01AG073482

VERI-T: A Phase 1 Placebo-Controlled Trial of Verdiperstat in Semantic Variant Primary Progressive Aphasia due to Underlying FTLD-TDP - Project Summary/Abstract

The proposed multi-site clinical trial will fill a critical unmet need for therapeutic development in Semantic Variant Primary Progressive Aphasia (SVPPA), a syndrome that is over 85% predictive of frontotemporal lobar degeneration with mislocalization of TDP-43 on autopsy (FTLD-TDP). We will thereby address the larger critical unmet need for therapeutic development in the greater spectrum of TDP-43 pathology, which is present in up to 20% of suspected Alzheimer's disease and over half of frontotemporal dementia.

We hypothesize that microglial myeloperoxidase (MPO), an enzyme responsible for the generation of microglial oxidative species, is a key therapeutic target in the pathogenesis of FTLD with TDP-4 mislocalization. We will therefore conduct a Phase 1 randomized, double-blind, placebo-controlled, sequential cohort, dose-ranging, tolerability, and preliminary pharmacodynamic study of two doses of Verdiperstat (BHV-3241), an orally administered MPO inhibitor, in patients with SVPPA.

As the first multi-site clinical trial focused on SVPPA, this project will establish the crucial organizational infrastructure to conduct future multicenter trials in this cohort, while leveraging existing clinical expertise and patient recruitment infrastructure from the large NIH-funded ARTFL-LEFFTDS longitudinal frontotemporal lobar degeneration (ALLFTD) multisite clinical research consortium.

In order to establish the appropriateness of follow-up Phase 2 trials, we will determine the safety and tolerability (Aim 1) and the pharmacokinetics (in blood and CSF) (Aim 2) of 300mg (low dose) and 600mg (high dose) BHV-3241, orally administered twice daily (BID) for 24 weeks in patients with SVPPA due to underlying FTLD-TDP. N=55 participants will be randomized overall to placebo (N=15), low dose (N=10), and high dose (N=30) BHV-3241 respectively.

Given the lack of established pharmacodynamic measures of drug efficacy in FTLD, we will also explore the effects of BHV-3241 on peripheral MPO activity, fluid and imaging biomarkers of neurodegeneration, unbiased CSF proteomics, and clinical status in FTLD-TDP (Aim 3). Our proposed discovery and longitudinal characterization of candidate measures of SVPPA biological and clinical severity will provide essential information, informing the design of future efficacy trials exploring BHV-3241 and other potential therapies in SVPPA and the larger spectrum of FTLD-TDP.

San Francisco Regents Of The University Of California

TO ENCOURAGE BIOMEDICAL, SOCIAL, AND BEHAVIORAL RESEARCH AND RESEARCH TRAINING DIRECTED TOWARD GREATER UNDERSTANDING OF THE AGING PROCESS AND THE DISEASES, SPECIAL PROBLEMS, AND NEEDS OF PEOPLE AS THEY AGE. THE NATIONAL INSTITUTE ON AGING HAS ESTABLISHED PROGRAMS TO PURSUE THESE GOALS. THE DIVISION OF AGING BIOLOGY EMPHASIZES UNDERSTANDING THE BASIC BIOLOGICAL PROCESSES OF AGING. THE DIVISION OF GERIATRICS AND CLINICAL GERONTOLOGY SUPPORTS RESEARCH TO IMPROVE THE ABILITIES OF HEALTH CARE PRACTITIONERS TO RESPOND TO THE DISEASES AND OTHER CLINICAL PROBLEMS OF OLDER PEOPLE. THE DIVISION OF BEHAVIORAL AND SOCIAL RESEARCH SUPPORTS RESEARCH THAT WILL LEAD TO GREATER UNDERSTANDING OF THE SOCIAL, CULTURAL, ECONOMIC AND PSYCHOLOGICAL FACTORS THAT AFFECT BOTH THE PROCESS OF GROWING OLD AND THE PLACE OF OLDER PEOPLE IN SOCIETY. THE DIVISION OF NEUROSCIENCE FOSTERS RESEARCH CONCERNED WITH THE AGE-RELATED CHANGES IN THE NERVOUS SYSTEM AS WELL AS THE RELATED SENSORY, PERCEPTUAL, AND COGNITIVE PROCESSES ASSOCIATED WITH AGING AND HAS A SPECIAL EMPHASIS ON ALZHEIMER'S DISEASE. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO EXPAND AND IMPROVE THE SBIR PROGRAM; TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT; TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT; AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS; TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT; AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.866 - Aging Research

National Institute on Aging (NIA) [HHS - NIH]

San Francisco, California 94143 United States

Single Zip Code

Early Stage Clinical Trials for the Spectrum of Alzheimers Disease and Age-related Cognitive Decline (R01 Clinical Trial Optional) (PAR-18-877)

Amendment Since initial award the End Date has been extended from 07/31/26 to 01/31/27 and the total obligations have increased 384% from $677,137 to $3,278,024.