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

Phase 2

Completed

Brief Summary: 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.

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Granulin and C9orf72	AL001	IV administration of AL001; 60 mg/kg, every 4 weeks \[q4w\]

Primary Outcome Measures

Name	Time	Method
Severity of TEAEs	197 weeks	Number of TEAEs categorized by severity
Severity of Treatment-Related TEAEs	197 weeks	Number of treatment-related TEAEs categorized by severity
Any TEAE Leading to Study Drug Discontinuation	197 weeks	Number of TEAEs leading to study drug discontinuation
Immunogenicity Antidrug Antibodies (ADA) Titer	97 weeks	Titer values of antidrug antibodies (ADAs) in participants receiving latozinemab at week 97/Part 1 end of study
Confirmatory Immunogenicity Antidrug Antibodies (ADA) Responses	97 weeks	Presence of confirmatory antidrug antibodies (ADAs) in participants who test positive for ADA at week 97 (Part 1 End of Study).
Change From Baseline in Sheehan Suicidality Tracking Scale	197 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Longitudinal Percent Change From Baseline of CSF PGRN	97 weeks	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.
Longitudinal Levels of Sortilin in WBCs	97 weeks	The overall change from baseline in Sortilin in WBCs.
Latozinemab Concentration in Serum	97 weeks	Serum concentration of Latozinemab at week 97.
Cmax of Latozinemab at Specified Timepoints	97 weeks	Maximum observed concentration of Latozinemab at week 96 of treatment.
Ctrough of Latozinemab at Specified Timepoints	97 weeks	Trough concentration of Latozinemab at week 96 of treatment
ARCmax of Latozinemab	61 weeks	Ratio of latozinemab Cmax at week 61 to the Cmax at week 1
Longitudinal Percent Change From Baseline in Plasma PGRN	97 weeks	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.

Locations (12): UCSF
🇺🇸
San Francisco, California, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases UT Health San Antonio
🇺🇸
San Antonio, Texas, United States
Lawson Health Research Institute, St. Joseph's
🇨🇦
London, Ontario, Canada
Sunnybrook Health Sciences Centre
🇨🇦
Toronto, Ontario, Canada
Technical University of Munich
🇩🇪
Munchen, Germany
University of Ulm
🇩🇪
Ulm, Germany
University of Brescia
🇮🇹
Brescia, Italy
Brain Research Center - PPDS
🇳🇱
Amsterdam, Netherlands
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UCSF
🇺🇸San Francisco, California, United States