Personalized Antisense Oligonucleotide Therapy for A Single Participant With CHCHD10 ALS

An Open-label Study of an Experimental Antisense Oligonucleotide Treatment for a Single Participant With Amyotrophic Lateral Sclerosis (ALS) Due to a Pathogenic Variant in CHCHD10

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

Study Overview

• Status: Active, not recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: nL-CHCHD-001

Detailed Description

This is an interventional study to evaluate the safety and efficacy of treatment with an individualized antisense oligonucleotide (ASO) treatment in a single participant with amyotrophic lateral sclerosis (ALS) due to a pathogenic variant in CHCHD10

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

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic

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 representative(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	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
Clinical Functioning	Change from baseline at 12-months post nL-CHCHD-001 administration in scores on vital capacity performance.	Baseline to 12 months
Disease biomarkers	Change from baseline at 12-months post nL-CHCHD-001 administration in serum/plasma and CSF neurofilament light chain levels	Baseline to 12 months
Survival	Change from baseline at 12-months post nL-CHCHD-001 administration in survival status	Baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Incidence and severity of adverse events	Baseline to 12 months
Safety and tolerability	Emergent abnormalities in physical exam	Baseline to 12 months
Safety and tolerability	Emergent abnormalities in neurological exam	Baseline to 12 months
Safety and tolerability	Emergent abnormalities in safety labs (CSF, chemistry, hematology, coagulation, and urinalysis)	Baseline to 12 months

Collaborators and Investigators

• Sponsor: n-Lorem Foundation
• Collaborators: Mayo Clinic
• Investigators: Principal Investigator: Björn E. Oskarsson, M.D., Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2024
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: April 24, 2024
• First Submitted That Met QC Criteria: April 26, 2024
• First Posted (Actual): April 30, 2024

Study Record Updates

• Last Update Posted (Actual): August 5, 2025
• Last Update Submitted That Met QC Criteria: July 31, 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: 23-011476

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
• product manufactured in and exported from the U.S.: No