Personalized Antisense Oligonucleotide Therapy for a Participant With TARDBP ALS

NCT07703462 | Enrolling By Invitation Phase 1 DMC FDA Drug

• 1 other identifier: NLF-TARDB-002-A
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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 TARDBP.

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Outcome Measures

Primary Outcomes (8)

• Clinical Functioning

  Change from baseline at 12-months post nL-TARDB-002 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-TARDB-002 administration in Slow Vital Capacity (SVC)

  Baseline to 12 months

• Clinical Functioning

  Change from baseline at 12-months post nL-TARDB-002 administration in Handheld Dynamometry (HHD)

  Baseline to 12 months

• Clinical Functioning

  Change from baseline at 12-months post nL-TARDB-002 administration in scores on Edinburgh Cognitive and Behavioral ALS Screen (ECAS).

  Baseline to 12 months

• Clinical Functioning

  Change from baseline at 12-months post nL-TARDB-002 administration in scores on ALS Cognitive Behavioral Screen (ALS-CBS).

  Baseline to 12 months

• Clinical Functioning

  Change from baseline at 12-months post nL-TARDB-002 administration in scores on Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5).

  Baseline to 12 months

• Survival

  Change from baseline at 12-months post nL-TARDB-002 administration in survival status

  Baseline to 12 months

• Disease Biomarkers

  Change from baseline at 12-months post nL-TARDB-002 administration in serum/plasma and CSF neurofilament light chain levels

  Baseline to 12 months

Other Outcomes (5)

• Safety and Tolerability

  Baseline to 12 months

• Safety and Tolerability

  Baseline to 12 months

• Safety and Tolerability

  Baseline to 12 months

Study Arms (1)

Open Label

EXPERIMENTAL

Drug: nL-TARDB-002

Interventions

nL-TARDB-002 DRUG

Personalized antisense oligonucleotide

Open Label

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent/assent provided by the participant (when appropriate), and/or participants 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Thomas Jefferson University: collaborator
• n-Lorem Foundation: lead

Study Sites (1)

Jefferson Health

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2026
• First Posted: July 14, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 14, 2026

Record last verified: 2026-07

Locations

US (1)