# Veri-T: A phase 1 Placebo-Controlled Trial of Verdiperstat in Semantic Variant Primary Progressive Aphasia Due to Underlying FTLD-TDP

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $677,137

## Abstract

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 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-324,
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.

## Key facts

- **NIH application ID:** 10280622
- **Project number:** 1R01AG073482-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** ADAM L. BOXER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $677,137
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10280622

## Citation

> US National Institutes of Health, RePORTER application 10280622, Veri-T: A phase 1 Placebo-Controlled Trial of Verdiperstat in Semantic Variant Primary Progressive Aphasia Due to Underlying FTLD-TDP (1R01AG073482-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10280622. Licensed CC0.

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