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: Active, not recruiting
• 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 (Estimated): 40
• 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
  • Munchen, 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: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Granulin; IV administration of AL001; 60 mg/kg, every 4 weeks [q4w]	Drug: AL001; 60 mg/kg of AL001 every 4 weeks
Experimental: 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
Part 1: Evaluation of safety and efficacy of AL001 as measured by the CDR® plus NACC FTLD-SB	The CDR® plus NACC FTLD assessment is the CDR® plus the Frontotemporal Dementia Behavior and Language Domain scores from the NACC FTLD module. Data for this scale will be captured through completion of the standard CDR and a domain-specific container form labeled Frontotemporal Dementia Behavior and Language Domains (FTD-BLD). The necessary information to rate these domains is obtained through a semi-structured interview of the participant and a reliable informant or collateral source (e.g., a caregiver).	96 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax) for AL001	Evaluate Cmax for concentration of AL001 at specified time points	96 weeks
Area under the curve concentration (AUC) for AL001	Evaluate AUC for concentration of AL001 at specified time points	96 weeks
Pharmacokinetics (PK) of AL001	Concentration of AL001 at specified time points	96 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.
• 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 (Estimated): January 28, 2026
• Study Completion (Estimated): June 2, 2026

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 (Actual): July 19, 2023
• Last Update Submitted That Met QC Criteria: July 18, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Language Disorders; Communication Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Dementia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain
• Other Study ID Numbers: AL001-2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No