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

Phase 2

Terminated

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Drug: Placebo; Drug: AL001

• Registration Number: NCT05053035
• Lead Sponsor: Alector Inc.

Brief Summary

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

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 Timeline

• Study First Submitted: 2021-09-01
• Study Start: 2021-09-02
• Study First Submitted QC: 2021-09-13
• Study First Posted: 2021-09-22
• Primary Completion: 2022-10-28
• Study Completion: 2022-10-28
• Results First Submitted: 2025-01-29
• Status Verified: 2025-05
• Results First Submitted QC: 2025-05-30
• Last Update Submitted: 2025-05-30
• Results First Posted: 2025-06-18
• Last Update Posted: 2025-06-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo every 4 weeks
AL001	AL001	AL001 every 4 weeks

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (3)

University of South Florida; 🇺🇸 Tampa, Florida, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States