Abstract Details

Title Baseline Characteristics for INFRONT-3: A Phase 3 Double-Blind, Placebo-Controlled 96-Week Study Evaluating Latozinemab in FTD-GRN

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P8 - Poster Session 8 (8:00 AM-9:00 AM)

Poster/Presentation
Number 3-005

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.

Authors/Disclosures
Tiffany W. Chow, MD, FAAN (Alector) PRESENTER	Dr. Chow has received personal compensation for serving as an employee of Alector, Inc.. Dr. Chow has stock in Alector, Inc.. Dr. Chow has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant on grant U19AG079774 with NIA.
Lawrence P. Carter, PhD (Alector)	Dr. Carter has received personal compensation for serving as an employee of Alector. Dr. Carter has stock in Alector. Dr. Carter has stock in Jazz Pharmaceuticals.
Barbara Borroni, MD	Dr. Borroni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Borroni has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley.
Catherine Mummery, PhD	Dr. Mummery has nothing to disclose.
Isabelle Le Ber, MD, PhD (AP HP)	Dr. Le Ber has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Prevail Therapeutics. Dr. Le Ber has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector.
Bradley F. Boeve, MD, FAAN (Mayo Clinic)	Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from EIP Pharma. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care.
Adam L. Boxer, MD, PhD (University of California, San Francisco)	An immediate family member of Dr. Boxer has received personal compensation for serving as an employee of Kaiser Permanente. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Oscotec. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arrowhead. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurocrine Biosciences. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Switch. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arvinas. Dr. Boxer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alector. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Dr. Boxer has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Transposon. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. Dr. Boxer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Boxer has stock in Alector. Dr. Boxer has stock in Arvinas. Dr. Boxer has stock in Neurovanda. The institution of Dr. Boxer has received research support from Biogen. The institution of Dr. Boxer has received research support from Eisai. The institution of Dr. Boxer has received research support from Regeneron. The institution of Dr. Boxer has received research support from NIH. The institution of Dr. Boxer has received research support from Bluefield Project-5. Dr. Boxer has received research support from Rainwater Charitable Foundation. Dr. Boxer has received research support from GHR Foundation. Dr. Boxer has received intellectual property interests from a discovery or technology relating to health care.
Megan Smithey, PhD	Dr. Smithey has received personal compensation for serving as an employee of Alector. Dr. Smithey has stock in Alector. Dr. Smithey has stock in Vir Biotechnology. Dr. Smithey has received intellectual property interests from a discovery or technology relating to health care.
Julie Huang, PhD (Alector)	Dr. Huang has received personal compensation for serving as an employee of Alector, Inc. Dr. Huang has stock in Alector.
Leonardo Guizzetti, PhD	The institution of Dr. Guizzetti has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for Everest Clinical Research.
Giacomo Salvadore, MD	Dr. Salvadore has received personal compensation for serving as an employee of Alector, Inc. Dr. Salvadore has stock in Alector, Inc..
Gary J. Romano, MD, PhD (Neurotherapeutic Development Advisors, LLC)	Dr. Romano has received personal compensation for serving as an employee of Alector. Dr. Romano has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for ALector. Dr. Romano has or had stock in Alector.

��ɫ��

��ɫ��