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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Frontotemporal Dementia

Intervention / Treatment
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* Drug: AL001


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Granulin<br>IV administration of AL001; 60 mg/kg, every 4 weeks [q4w] | Drug: AL001<br>* 60 mg/kg of AL001 every 4 weeks<br>|
| Experimental: C9orf72<br>IV administration of AL001; 60 mg/kg, every 4 weeks [q4w] | Drug: AL001<br>* 60 mg/kg of AL001 every 4 weeks<br>|

What is the study measuring?
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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 |