A Phase 2 Study to Evaluate Safety of Long-term AL001 Dosing in Frontotemporal Dementia (FTD) Patients (INFRONT-2)

A Phase 2, Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AL001 in Heterozygous Carriers of Granulin or C9orf72 Mutations Causative of Frontotemporal Dementia

A Phase 2 open label study evaluating the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AL001 in participants with a Granulin mutation or C9orf72 mutation causative of frontotemporal dementia.

Study Overview

• Status: Completed
• Conditions: Frontotemporal Dementia
• Intervention / Treatment: Drug: AL001

Detailed Description

This is a Phase 2, multicenter, open label study evaluating the safety, tolerability, PK and PD of AL001 administered intravenously in participants with a Granulin mutation or C9orf72 mutation causative of frontotemporal dementia.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 4V2
      • Lawson Health Research Institute, St. Joseph's
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
• Germany
  • München, Germany, 81675
    • Technical University of Munich
  • Ulm, Germany, 89081
    • University of Ulm
• Italy
  • Brescia, Italy, 25123
    • University of Brescia
• Netherlands
  • Amsterdam, Netherlands, 1081GN
    • Brain Research Center - PPDS
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus University Medical Center
• United Kingdom
  • London, United Kingdom, WC1N 3BG
    • University College London
• United States
  • California
    • San Francisco, California, United States, 94158
      • UCSF
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Texas
    • San Antonio, Texas, United States, 78229
      • The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases UT Health San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• At screening, female participants must be nonpregnant and nonlactating
• In good physical health on the basis of no clinically significant findings from medical history, physical examinations (PEs), laboratory tests, ECGs, and vital signs.
• Participant is a carrier of a loss of function progranulin gene (GRN) mutation or carrier of a hexanucleotide repeat expansion C9orf72 mutation

Exclusion Criteria:

• Known history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric, human, or humanized antibodies or fusion proteins.
• History of alcohol abuse or substance abuse
• Participant resides in a skilled nursing facility, convalescent home, or long term care facility

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Granulin and C9orf72; IV administration of AL001; 60 mg/kg, every 4 weeks [q4w]	Drug: AL001; 60 mg/kg of AL001 every 4 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of TEAEs	Number of TEAEs categorized by severity	197 weeks
Severity of Treatment-Related TEAEs	Number of treatment-related TEAEs categorized by severity	197 weeks
Any TEAE Leading to Study Drug Discontinuation	Number of TEAEs leading to study drug discontinuation	197 weeks
Immunogenicity Antidrug Antibodies (ADA) Titer	Titer values of antidrug antibodies (ADAs) in participants receiving latozinemab at week 97/Part 1 end of study	97 weeks
Confirmatory Immunogenicity Antidrug Antibodies (ADA) Responses	Presence of confirmatory antidrug antibodies (ADAs) in participants who test positive for ADA at week 97 (Part 1 End of Study).	97 weeks
Change From Baseline in Sheehan Suicidality Tracking Scale	The Sheehan Suicidality Tracking Scale (S-STS) is a structured assessment tool used to evaluate the presence, severity, and frequency of suicidal ideation and behavior. It includes items that address passive thoughts of death, active suicidal ideation, intent, planning, suicide attempts, and non-suicidal self-injury. The S-STS total score ranges from 0 to 64, based on 16 items each rated from 0 (not at all) to 4 (extremely), with higher scores indicating greater severity of suicidal ideation, intent, or behavior. The total score provides a quantitative measure of suicidality severity and is sensitive to change over time, making it suitable for clinical monitoring and research use.	197 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal Percent Change From Baseline of CSF PGRN	The percent change from baseline to specified timepoints of PGRN in CSF. The baseline visit is labeled as week 1 and therefore the 96th week is labeled as week 97.	97 weeks
Longitudinal Percent Change From Baseline in Plasma PGRN	The percent change from baseline to specified timepoints for PGRN in plasma. The baseline visit is labeled as week 1 and therefore the 96th week is labeled as week 97.	97 weeks
Longitudinal Levels of Sortilin in WBCs	The overall change from baseline in Sortilin in WBCs.	97 weeks
Latozinemab Concentration in Serum	Serum concentration of Latozinemab at week 97.	97 weeks
Cmax of Latozinemab at Specified Timepoints	Maximum observed concentration of Latozinemab at week 96 of treatment.	97 weeks
Ctrough of Latozinemab at Specified Timepoints	Trough concentration of Latozinemab at week 96 of treatment	97 weeks
ARCmax of Latozinemab	Ratio of latozinemab Cmax at week 61 to the Cmax at week 1	61 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 2: Assess the long-term safety and tolerability of IV administration of AL001 as measured by the CDR® plus NACC FTLD-SB	The primary objective of the OLE period of the study is to assess the long term safety and tolerability of AL001 in participants who have completed 96 weeks of treatment on Part 1 of the study	96 Weeks

Collaborators and Investigators

• Sponsor: Alector Inc.
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Peter Ljubenkov, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2019
• Primary Completion (Actual): June 5, 2024
• Study Completion (Actual): June 5, 2024

Study Registration Dates

• First Submitted: May 14, 2019
• First Submitted That Met QC Criteria: June 13, 2019
• First Posted (Actual): June 17, 2019

Study Record Updates

• Last Update Posted (Estimated): December 5, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Metabolic Diseases; Neurocognitive Disorders; Dementia; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Frontotemporal Lobar Degeneration; Nutritional and Metabolic Diseases; Frontotemporal Dementia
• Other Study ID Numbers: AL001-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No