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

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

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

Study Overview

• Status: Terminated
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: AL001; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AL001; AL001 every 4 weeks	Drug: AL001; Administered via intravenous (IV) infusion
Placebo Comparator: Placebo; Placebo every 4 weeks	Drug: Placebo; Administered via intravenous (IV) infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Safety and Tolerability of AL001 Measured by Number of Subjects With Adverse Events	Count of participants with adverse events during the study treatment period	24 weeks
Immunogenicity of AL001	Count of participants positive for Anti-drug Antibodies (ADAs) to AL001 at week 24	Week 24
Pharmacokinetics (PK) of AL001 in Serum	Concentration of AL001 in Serum at week 24	Week 24
Pharmacokinetics (PK) of AL001 in CSF	Concentration of AL001 in Cerebrospinal fluid (CSF) at week 24	Week 24
Change From Baseline in Plasma Progranulin	Evaluate the change from baseline to week 24 in plasma progranulin levels	24 weeks
Change From Baseline in CSF Progranulin	Evaluate the change from baseline to week 24 in Cerebrospinal fluid (CSF) progranulin levels	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Plasma Neurofilament Light Chain	Evaluate the change from baseline to week 24 in plasma neurofilament light chain levels	24 weeks
Change From Baseline in CSF Neurofilament Light Chain	Evaluate change from baseline to week 24 in Cerebrospinal fluid (CSF) neurofilament light chain levels	24 weeks

Collaborators and Investigators

• Sponsor: Alector Inc.
• Investigators: Principal Investigator: Sabrina Paganoni, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2021
• Primary Completion (Actual): October 28, 2022
• Study Completion (Actual): October 28, 2022

Study Registration Dates

• First Submitted: September 1, 2021
• First Submitted That Met QC Criteria: September 13, 2021
• First Posted (Actual): September 22, 2021

Study Record Updates

• Last Update Posted (Actual): June 18, 2025
• Last Update Submitted That Met QC Criteria: May 30, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: AL001-ALS-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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