A Phase 2 Study to Evaluate AL001 in C9orf72-Associated ALS

Study Overview
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Brief Summary
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A phase 2 double-blind, placebo-controlled study of AL001 in participants with C9orf72-associated ALS.

Detailed Description
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This is a phase 2 double-blind, placebo-controlled trial to test the safety, tolerability, pharmacokinetics, and pharmacodynamics of AL001 in participants with C9orf72-associated Amyotrophic Lateral Sclerosis.

Official Title
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A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AL001 in C9orf72-Associated Amyotrophic Lateral Sclerosis

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: AL001
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmation of C9orf72 mutation Diagnosis of ALS by revised El Escorial criteria Time since onset of muscle weakness due to ALS ≤36 months at the time of the Screening Visit Slow Vital Capacity (VC) ≥50% of predicted capacity at the time of the Screening Visit If taking riluzole, must be on a stable dose of riluzole for at least 30 days prior to the Screening Visit. Riluzole naive participants are allowed. If taking edaravone, must have completed at least one cycle of edaravone prior to the Screening Visit and plan to continue edaravone during the study. Edaravone naive participants are allowed. Females must not be pregnant, breastfeeding or planning to conceive within the study period. Males must agree to use acceptable contraception Capable of providing informed consent at the Screening visit and complying with study procedures throughout the study Exclusion Criteria: Clinically significant, unstable, medical condition (other than ALS) Clinically significant heart disease, liver disease or kidney disease Cognitive impairment or dementia Current uncontrolled hypertension History of unresolved cancer Any experimental gene therapy Any experimental vaccine (any vaccine against COVID-19 either approved or administered under an Emergency Use Authorization is allowed)

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AL001<br>AL001 every 4 weeks | Drug: AL001<br>* Administered via intravenous (IV) infusion<br>|
| Placebo Comparator: Placebo<br>Placebo every 4 weeks | Drug: Placebo<br>* Administered via intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of safety and tolerability of AL001 measured by number of subjects with adverse events | Incidence of adverse events during the study treatment period | 32 weeks | 
| Pharmacokinetics (PK) of AL001 | Concentration of AL001 at specified time points | 32 weeks | 
| Maximum plasma concentration (Cmax) for AL001 | Evaluate Cmax for concentration of AL001 at specified time points | 32 weeks | 
| Area under the curve concentration (AUC) for AL001 | Evaluate AUC for concentration of AL001 at specified time points | 32 weeks | 
| Change from baseline in serum progranulin | Evaluate serum progranulin levels at pre-specified timepoints | 32 weeks | 
| Change from baseline in CSF progranulin | Evaluate CSF progranulin levels at pre-specified timepoints | 32 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in plasma neurofilament light chain | Evaluate plasma neurofilament light chain levels at pre-specified timepoints | 32 weeks | 
| Change from baseline in CSF neurofilament light chain | Evaluate CSF neurofilament light chain levels at pre-specified timepoints | 32 weeks |