A Study of LY4298445 in Healthy Participants and Participants With Systemic Lupus Erythematosus (SLE) or Rheumatoid Arthritis (RA)

NCT07276958 | Recruiting Phase 1

• 2 other identifiers: 27747J6S-MC-KCAA
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate the safety and tolerability of LY4298445 in healthy participants and in participants with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). Participation in the study will last up to approximately 52 weeks.

Conditions

Healthy; Systemic Lupus Erythematosus; Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration

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

  Baseline up to Week 52

Secondary Outcomes (3)

• Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY4298445

  Baseline up to Approximately Week 57

• PK: Maximum Concentration (Cmax) of LY4298445

  Baseline up to Week 52

• Pharmacodynamic (PD): Degree of Peripheral B Cell Depletion Following Biopsy in Participants

  Baseline up to Week 52

Study Arms (6)

LY4298445 (Part A1)

EXPERIMENTAL

Single-ascending dose (SAD) of LY4298445 administered subcutaneously (SC) or intravenously (IV) in healthy participants

Drug: LY4298445

LY4298445 Placebo (Part A1)

PLACEBO COMPARATOR

SAD of LY4298445 administered SC or IV in healthy participants

Drug: LY4298445

LY4298445 (Part A2)

EXPERIMENTAL

SAD of LY4298445 administered SC in participants with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA)

Drug: LY4298445

LY4298445 (Part B)

EXPERIMENTAL

Multiple-ascending doses (MAD) of LY4298445 administered SC in participants with SLE or RA

Drug: LY4298445

LY4298445 (Part C)

EXPERIMENTAL

Single dose of LY4298445 administered SC in healthy Japanese and Chinese participants

Drug: LY4298445

LY4298445 Placebo (Part C)

PLACEBO COMPARATOR

Single dose of LY4298445 administered SC in healthy Japanese and Chinese participants

Drug: LY4298445

Interventions

LY4298445 DRUG

Administered SC

LY4298445 (Part A1); LY4298445 (Part A2); LY4298445 (Part B); LY4298445 (Part C); LY4298445 Placebo (Part A1); LY4298445 Placebo (Part C)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy participants between the ages of 18 and 55 years.
• Have body weight of at least 50 kilograms (kg) and body mass index (BMI) between 18 and 32 kilogram per square meter (kg/m²), inclusive.
• Participants with Systemic Lupus Erythematosus (SLE)
• Are 18 to 75 years of age, inclusive.
• Have body weight between 45 and 145 kg, inclusive, and BMI between 18 and 35 kg/m², inclusive.
• Have a clinical diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria at least 6 months prior to screening.
• Participants with Rheumatoid Arthritis (RA)
• Are 18 to 75 years of age, inclusive.
• Have body weight between 45 and 145 kg, inclusive, and BMI between 18 and 35 kg/m², inclusive.
• Have a diagnosis of adult-onset RA for at least 6 months prior to screening, as defined by the 2010 ACR/EULAR classification criteria
• Have Disease Activity Score in 28 joints (DAS28)-high-sensitivity C-reactive protein (hsCRP) greater than or equal to 4.4.
• Have positive test results for rheumatoid factor or anti-citrullinated peptide antibodies
• Have had a history of failure (an inadequate response, intolerance, or loss of response) to at least 2 advanced therapies (biological disease-modifying antirheumatic drug \[bDMARD\] or targeted synthetic DMARD \[tsDMARD\]) after failing a conventional synthetic DMARD (csDMARD).

You may not qualify if:

• Have known allergies to LY4298445, related compounds, or any components of the formulation
• Are individuals assigned female at birth (AFAB) who are lactating or have a positive pregnancy test at screening or Day -1.
• Have severe active lupus-associated renal disease (lupus nephritis) defined clinically and/or by
• urine protein/creatinine ratio greater than 200 milligrams per millimole (mg/mmol) (as an estimate of approximate proteinuria greater than 2 reams (g) per day) or
• an estimated glomerular filtration rate (eGFR) less than 40 milliliters per minute (mL/min)/1.73 m² at screening, as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) 2021.
• requiring hemodialysis within 6 months prior to screening
• Have active central nervous system lupus as defined by ACR nomenclature for neuropsychiatric lupus syndromes and as captured by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K); seizure, psychosis, organic brain syndrome, visual disturbance, cranial nerve disorder, lupus headache, and cerebrovascular accident, within 2 months prior to screening
• Have a Class 4 RA according to the ACR revised criteria

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

Nucleus Network

Brisbane, 4006, Australia

RECRUITING

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic 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)

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: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2025
• First Posted: December 11, 2025
• Study Start: February 4, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028
• Last Updated: June 4, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)