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

Phase 2

Active, not recruiting

• Conditions: Frontotemporal Dementia
• Interventions: Drug: AL001

• Registration Number: NCT03987295
• Lead Sponsor: Alector Inc.

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.

Study Timeline

• Study First Submitted: 2019-05-14
• Study First Submitted QC: 2019-06-13
• Study First Posted: 2019-06-17
• Study Start: 2019-09-27
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-18
• Last Update Posted: 2023-07-19
• Primary Completion: 2026-01-28
• Study Completion: 2026-06-02

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 40

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Part 1: Evaluation of safety and efficacy of AL001 as measured by the CDR® plus NACC FTLD-SB	96 weeks	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).

Secondary Outcome Measures

Name	Time	Method
Area under the curve concentration (AUC) for AL001	96 weeks	Evaluate AUC for concentration of AL001 at specified time points
Pharmacokinetics (PK) of AL001	96 weeks	Concentration of AL001 at specified time points
Maximum plasma concentration (Cmax) for AL001	96 weeks	Evaluate Cmax for concentration of AL001 at specified time points

Trial Locations

Locations (12)

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Erasmus University Medical Center; 🇳🇱 Rotterdam, Netherlands

University College London; 🇬🇧 London, United Kingdom

Technical University of Munich; 🇩🇪 Munchen, Germany

Lawson Health Research Institute, St. Joseph's; 🇨🇦 London, Ontario, Canada

University of Ulm; 🇩🇪 Ulm, Germany

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

UCSF; 🇺🇸 San Francisco, California, 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

University of Brescia; 🇮🇹 Brescia, Italy

Brain Research Center - PPDS; 🇳🇱 Amsterdam, Netherlands