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

• ClinicalTrials.gov Identifier: NCT03987295
• Recruitment Status: Active, not recruiting
• First Posted: June 17, 2019
• Last Update Posted: July 1, 2022
• Sponsor: Alector Inc.
• Information provided by (Responsible Party): Alector Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Frontotemporal Dementia	Drug: AL001	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: September 27, 2019
• Estimated Primary Completion Date: January 28, 2026
• Estimated Study Completion Date: June 2, 2026

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Part 1: Evaluation of safety and efficacy of AL001 as measured by the CDR® plus NACC FTLD-SB [ Time Frame: 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 :

1. Maximum plasma concentration (Cmax) for AL001 [ Time Frame: 96 weeks ]
   Evaluate Cmax for concentration of AL001 at specified time points
2. Area under the curve concentration (AUC) for AL001 [ Time Frame: 96 weeks ]
   Evaluate AUC for concentration of AL001 at specified time points
3. Pharmacokinetics (PK) of AL001 [ Time Frame: 96 weeks ]
   Concentration of AL001 at specified time points

Other Outcome Measures:

1. Part 2: Assess the long-term safety and tolerability of IV administration of AL001 as measured by the CDR® plus NACC FTLD-SB [ Time Frame: 96 Weeks ]
   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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

UCSF

San Francisco, California, United States, 94158

United States, Minnesota

Mayo Clinic

Rochester, Minnesota, United States, 55905

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

United States, Texas

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

San Antonio, Texas, United States, 78229

Canada, Ontario

Lawson Health Research Institute, St. Joseph's

London, Ontario, Canada, N6A 4V2

Sunnybrook Health Sciences Centre

Toronto, Ontario, Canada, M4N 3M5

Germany

Technical University of Munich

Munchen, Germany, 81675

University of Ulm

Ulm, Germany, 89081

Italy

University of Brescia

Brescia, Italy, 25123

Netherlands

Brain Research Center - PPDS

Amsterdam, Netherlands, 1081GN

Erasmus University Medical Center

Rotterdam, Netherlands, 3015 GD

United Kingdom

University College London

London, United Kingdom, WC1N 3BG

Sponsors and Collaborators

Alector Inc.

Investigators

• Principal Investigator: Peter Ljubenkov, MD; University of California, San Francisco

More Information

• Responsible Party: Alector Inc.
• ClinicalTrials.gov Identifier: NCT03987295
• Other Study ID Numbers: AL001-2
• First Posted: June 17, 2019
• Last Update Posted: July 1, 2022
• Last Verified: June 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Dementia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Neurodegenerative Diseases; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Aphasia; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations