A Study of LY4256984 in Participants With Sporadic Amyotrophic Lateral Sclerosis

A Multiple Ascending Dose Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intrathecally Administered LY4256984 in Participants With Sporadic Amyotrophic Lateral Sclerosis

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.

Study Overview

• Status: Recruiting
• Conditions: ALS (Amyotrophic Lateral Sclerosis)
• Intervention / Treatment: Drug: Placebo; Drug: LY4256984

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or; Phone Number: 1-317-615-4559; Email: LillyTrials@Lilly.com
• Study Contact Backup: Name: Physicians interested in becoming principal investigators please contact; Email: clinical_inquiry_hub@lilly.com

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
    • Principal Investigator: Philip Van Damme
    • Contact: Phone Number: (321) 634-4280
• Canada
  • Calgary, Canada, T2N4Z6
    • Not yet recruiting
    • Heritage Medical Research Clinic
    • Contact: Phone Number: 403-210-7006
    • Principal Investigator: Theodore Mobach
  • Edmonton, Canada, T6G 2X8
    • Not yet recruiting
    • Walter Mackenzie Health Sciences Centre
    • Contact: Phone Number: 780.248.1089
    • Principal Investigator: Peter Dobrowolski
  • London, Canada, N6A 5A5
    • Not yet recruiting
    • London Health Sciences Centre
    • Principal Investigator: Christen Shoesmith
    • Contact: Phone Number: 519-663-3597
  • Montreal, Canada, H3A 2B4
    • Recruiting
    • Montreal Neurological Institute and Hospital
    • Principal Investigator: Angela Genge
    • Contact: Phone Number: 514-449-8741
  • Toronto, Canada, M4N 3M5
    • Recruiting
    • Sunnybrook Research Institute
    • Contact: Phone Number: 4134806860
    • Principal Investigator: Agessandro Abrahao
• Germany
  • Lübeck, Germany, 23538
    • Recruiting
    • Universitatsklinikum Schleswig-Holstein
    • Principal Investigator: Julian Grosskreutz
    • Contact: Phone Number: 4936419323426
  • Rostock, Germany, 18147
    • Not yet recruiting
    • Universitätsmedizin Rostock Sektion für Translationale Neurodegeneration "Albrecht Kossel" Klinik und Poliklinik für Neurologie
    • Contact: Phone Number: 49 (0)381 494-9541
    • Principal Investigator: Andreas Hermann
  • Ulm, Germany, 89081
    • Not yet recruiting
    • Universitätsklinikum Ulm
    • Principal Investigator: Jochen Weishaupt
    • Contact: Phone Number: (497315) 006-3099
• Netherlands
  • Utrecht, Netherlands, 3584
    • Recruiting
    • Universitair Medisch Centrum Utrecht
    • Principal Investigator: Leonard van den Berg
    • Contact: Phone Number: 31887553204
• Spain
  • L'Hospitalet de Llobregat, Spain, 8907
    • Recruiting
    • Hospital Universitario de Bellvitge
    • Contact: Phone Number: +34 933359011 ext 8486
    • Principal Investigator: Monica Povedano
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitari i Politecnic La Fe
    • Principal Investigator: Juan Francisco Vazquez Costa
    • Contact: Phone Number: 34644490025

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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)

Exclusion Criteria:

• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY4256984 (Cohorts 1-4); Multiple ascending doses (MAD) of LY4256984 administered intrathecally (IT)	Drug: LY4256984; Administered IT
Placebo Comparator: Placebo; Administered IT	Drug: Placebo; Administered IT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Plasma Area Under the Concentration Versus Time Curve (AUC) of LY4256984	PK: Plasma AUC of LY4256984	Baseline up to Approximately Day 253
PK: Plasma Maximum Concentration (Cmax) of LY4256984	PK: Plasma Cmax of LY4256984	Baseline up to Approximately Day 253
PK: Cerebrospinal Fluid Concentrations (CSF) of LY4256984	PK: CSF Concentrations of LY4256984	Baseline up to Approximately Day 253

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 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 record dates

Study Major Dates

• Study Start (Actual): August 5, 2025
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: July 31, 2025
• First Submitted That Met QC Criteria: August 1, 2025
• First Posted (Actual): August 3, 2025

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Nutritional and Metabolic Diseases; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: 27427; J6I-MC-OWAA (Other Identifier: Eli Lilly and Company); U1111-1321-6118 (Other Identifier: World Health Organization (WHO)); 2025-521295-6 (Other Identifier: EU CTR #)

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