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

NCT03987295 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AL001-2
• Study Type: interventional
• Target: 33
• Locations: 6 countries
• Sites: 12

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.

Conditions

Frontotemporal Dementia

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (7)

• Longitudinal Percent Change From Baseline of CSF PGRN

  97 weeks

• Longitudinal Percent Change From Baseline in Plasma PGRN

  97 weeks

• Longitudinal Levels of Sortilin in WBCs

  97 weeks

• Latozinemab Concentration in Serum

  97 weeks

• Cmax of Latozinemab at Specified Timepoints

  97 weeks

Study Arms (1)

Granulin and C9orf72

EXPERIMENTAL

IV administration of AL001; 60 mg/kg, every 4 weeks \[q4w\]

Drug: AL001

Interventions

AL001 DRUG

60 mg/kg of AL001 every 4 weeks

Granulin and C9orf72

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alector Inc.: lead
• GlaxoSmithKline: collaborator

Study Sites (12)

UCSF

San Francisco, California, 94158, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

The Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

Lawson Health Research Institute, St. Joseph's

London, Ontario, N6A 4V2, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Technical University of Munich

München, 81675, Germany

Location

University of Ulm

Ulm, 89081, Germany

Location

University of Brescia

Brescia, 25123, Italy

Location

Brain Research Center - PPDS

Amsterdam, 1081GN, Netherlands

Location

Erasmus University Medical Center

Rotterdam, 3015 GD, Netherlands

Location

University College London

London, WC1N 3BG, United Kingdom

Location

MeSH Terms

Conditions

Frontotemporal Dementia

Condition Hierarchy (Ancestors)

Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders; Mental Disorders

Limitations and Caveats

The study had the following limitations: * No placebo control arm * Small number of participants * A high number of participants discontinued the study due to disease progression

Results Point of Contact

• Title: Alector Medical Information
• Organization: Alector

medinfo@alector.com

650-826-2454

Study Officials

• Peter Ljubenkov, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2019
• First Posted: June 17, 2019
• Study Start: September 27, 2019
• Primary Completion: June 5, 2024
• Study Completion: June 5, 2024
• Last Updated: December 5, 2025
• Results First Posted: August 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); CA (2); IT (1); GB (1); NL (2); DE (2)