Objective:

The objective is to describe the baseline characteristics of participants enrolled in INFRONT-3 (NCT04374136).

Background:

Latozinemab is a human monoclonal antibody being developed for the treatment of frontotemporal dementia (FTD) due to a heterozygous progranulin gene (GRN) mutation. Latozinemab blocks and downregulates the sortilin receptor, which regulates plasma and brain progranulin (PGRN) levels. Prior studies demonstrated that latozinemab increased PGRN to physiologic levels and slowed disease progression relative to matched controls. Herein, we describe the baseline characteristics for participants in the INFRONT-3 study.

Design/Methods:

INFRONT-3 is a pivotal Phase 3 multicenter, randomized, double-blind, placebo-controlled 96-week study. Participants have a baseline CDR plus NACC FTLD-SB score ≤0.5 with elevated serum NfL (At-risk Cohort), or a CDR plus NACC FTLD-SB score of >0.5 with 1 or more of 6 behavioral/cognitive symptoms required for diagnosis of possible bvFTD or PPA (Symptomatic Cohort).

Results:

A total of 119 participants (103 Symptomatic) were enrolled with global CDR score of 0 (n=15), 0.5 (n=25), 1 (n=47), or 2 (n=32). Mean age was 62 years (range: 37-85), with 51% female, and 89% Caucasian. The At-risk Cohort had a mean ±SD CDR-SB of 0.0±0.13 and a median serum NfL of 14.4 pg/mL (range 7.8-42.9). The Symptomatic Cohort had a mean ±SD CDR-SB of 6.9±4.05 and a median serum NfL of 66.9 pg/mL (range 6.5-190.0). Symptomatic participants were diagnosed with bvFTD (64), PPA (28), or both bvFTD and PPA (7).

Conclusions:

INFRONT-3 is designed to provide evidence of efficacy and safety for latozinemab, a potential first-in-class approach for treating FTD-GRN in a representative population spanning disease severity.