A Study of LY4256984 in Participants With Sporadic Amyotrophic Lateral Sclerosis

NCT07100119 | Recruiting Phase 1

• 4 other identifiers: 27427J6I-MC-OWAA2025-521295-6U1111-1321-6118
• Study Type: interventional
• Target: 32
• Locations: 5 countries
• Sites: 12

Brief Summary

The purpose of this study is to evaluate how well LY4256984 is tolerated and what side effects may occur in participants with sporadic amyotrophic lateral sclerosis (ALS). The study drug will be administered intrathecally (IT) into the spine. Blood tests will be performed to check how much LY4256984 gets into the bloodstream and how long it takes the body to eliminate it.

Conditions

ALS (Amyotrophic Lateral Sclerosis)

Outcome Measures

Primary Outcomes (1)

• Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs), Serious Adverse Event(s) (SAEs), and Adverse Event(s) (AEs) Considered by the Investigator to be Related to Study Drug Administration

  A summary of TEAEs, SAEs, and AEs regardless of causality, will be reported in the Reported Adverse Events module

  Baseline up to Approximately Day 253

Secondary Outcomes (3)

• Pharmacokinetics (PK): Plasma Area Under the Concentration Versus Time Curve (AUC) of LY4256984

  Baseline up to Approximately Day 253

• PK: Plasma Maximum Concentration (Cmax) of LY4256984

  Baseline up to Approximately Day 253

• PK: Cerebrospinal Fluid Concentrations (CSF) of LY4256984

  Baseline up to Approximately Day 253

Study Arms (2)

LY4256984 (Cohorts 1-4)

EXPERIMENTAL

Multiple ascending doses (MAD) of LY4256984 administered intrathecally (IT)

Drug: LY4256984

Placebo

PLACEBO COMPARATOR

Administered IT

Drug: Placebo

Interventions

LY4256984 DRUG

Administered IT

LY4256984 (Cohorts 1-4)

Placebo DRUG

Administered IT

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have a definite, possible, or probable diagnosis of sporadic amyotrophic lateral sclerosis (ALS) made by a physician experienced with the management of ALS
• ALS symptom onset as determined by the Investigator within 24 months of Screening
• Have a body mass index (BMI) within the range of greater than or equal to 18.0 and less than or equal to 35.0 kilogram per square meter (kg/m²) (inclusive)

You may not qualify if:

• Have a history or presence of medical illness including, but not limited to, any cardiovascular, renal, hepatic, gastrointestinal, respiratory, hematological, endocrine, psychiatric, or neurological disease, convulsions, or any clinically significant laboratory abnormality
• Have a history of another neurodegenerative disease or significant dementia/severe cognitive problems
• Have serum alanine aminotransferase (ALT), aspartate transferase (AST), or total bilirubin levels greater than 2 x upper limit of normal.
• Have a significant renal impairment (estimated glomerular filtration rate \<60 milliliters per minute \[mL/min\]/1.73 m²).
• Have a 12-lead electrocardiogram (ECG) abnormality at screening, in the opinion of the investigator, that increases the risks associated with participating in the study
• Show clinically significant abnormalities in lumbar spine previously known or determined by screening lumbar X-ray or fluoroscopy (if performed)

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (12)

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

Heritage Medical Research Clinic

Calgary, T2N4Z6, Canada

NOT YET RECRUITING

Walter Mackenzie Health Sciences Centre

Edmonton, T6G 2X8, Canada

NOT YET RECRUITING

London Health Sciences Centre

London, N6A 5A5, Canada

NOT YET RECRUITING

Montreal Neurological Institute and Hospital

Montreal, H3A 2B4, Canada

RECRUITING

Sunnybrook Research Institute

Toronto, M4N 3M5, Canada

RECRUITING

Universitätsklinikum Schleswig-Holstein

Lübeck, 23538, Germany

RECRUITING

Universitätsmedizin Rostock Sektion für Translationale Neurodegeneration "Albrecht Kossel" Klinik und Poliklinik für Neurologie

Rostock, 18147, Germany

NOT YET RECRUITING

Universitätsklinikum Ulm

Ulm, 89081, Germany

NOT YET RECRUITING

Universitair Medisch Centrum Utrecht

Utrecht, 3584, Netherlands

RECRUITING

Hospital Universitario de Bellvitge

L'Hospitalet de Llobregat, 8907, Spain

RECRUITING

Hospital Universitari i Politecnic La Fe

Valencia, 46026, Spain

RECRUITING

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 Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Central Study Contacts

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

CONTACT

1-317-615-4559; LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

CONTACT

clinical_inquiry_hub@lilly.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2025
• First Posted: August 3, 2025
• Study Start: August 5, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); DE (3); CA (5); NL (1); ES (2)