Personalized Antisense Oligonucleotide for Participants With CHCHD10 ALS

An Open-Label Study of an Experimental Antisense Oligonucleotide Treatment for Amyotrophic Lateral Sclerosis (ALS) Due to an Arg15Leu Pathogenic Variant in CHCHD10

This research project entails delivery of a personalized antisense oligonucleotide (ASO) drug designed for individual participants with amyotrophic lateral sclerosis (ALS) due to a pathogenic variant in CHCHD10

Study Overview

• Status: Enrolling by invitation
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: nL-CHCHD-001

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University, Irving Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Informed consent/assent provided by the participant (when appropriate), and/or participant's parent(s) or legally authorized representatives(s)
• Ability to travel to the study site and adhere to study related follow-up examinations and/or procedures and provide access to participant's medical records
• Genetically confirmed neurological disorder

Exclusion Criteria:

• Participant has any condition that in the opinion of the Site Investigator would ultimately prevent the completion of study procedures
• Use of an investigational medication within less than 5 half-lives of the drug at enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open Label nL-CHCHD-001	Drug: nL-CHCHD-001; Personalized antisense oligonucleotide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Functioning	Change from baseline at 12-months post nL-CHCHD-001 administration in scores on Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R).	Baseline to 12 months
Clinical Functioning	Change from baseline at 12-months post nL-CHCHD-001 administration in scores on ALS Cognitive Behavioral Screen (ALS-CBS)	Baseline to 12 months
Clinical Functioning	Change from baseline at 12-months post nL-CHCHD-001 administration in scores on Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5)	Baseline to 12 months
Motor Function	Change from baseline at 12-months post nL-CHCHD-001 administration in Slow Vital Capacity (SVC)	Baseline to 12 months
Motor Function	Change from baseline at 12-months post nL-CHCHD-001 administration in muscle strength as quantified by Handheld Dynamometry (HHD)	Baseline to 12 months
Clinical Functioning	Change from baseline at 12-months post nL-CHCHD-001 administration in Edinburgh Cognitive and Behavioral ALS Screen (ECAS) score	Baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability	Emergent abnormalities in neurological exam (changes in mental status, gait, cerebellar, cranial nerve, motor, reflex, and sensations compared to baseline)	Baseline to 12 months
Disease Biomarkers	Change from baseline at 12-months post nL-CHCHD-001 administration in serum and CSF neurofilament light chain levels	Baseline to 12 months
Safety and Tolerability	Incidence and severity of Adverse Events	Baseline to 12 months
Safety and tolerability	Emergent abnormalities in physical exam (changes in appearance, skin, neck, ears, nose, throat, heart/lungs, abdomen, lymph nodes, and extremities compared to baseline)	Baseline to 12 months
Safety and tolerability	Emergent abnormalities in laboratory analyses (results outside of normal range for CSF, chemistry, hematology, coagulation, and urinalysis)	Baseline to 12 months

Collaborators and Investigators

• Sponsor: n-Lorem Foundation
• Collaborators: Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: May 12, 2025
• First Submitted That Met QC Criteria: July 23, 2025
• First Posted (Actual): July 31, 2025

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 23, 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: AAAV3923

Drug and device information, study documents

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