LY4298445 in healthy adults and people with lupus or rheumatoid arthritis

A Phase 1, Multicenter, Randomized, Placebo-Controlled, Participant-Blind, Single-Ascending Dose Study of LY4298445 in Healthy Participants and an Open-Label Single-Ascending Dose and Multiple-Ascending Dose Study of LY4298445 in Participants With Systemic Lupus Erythematosus or Rheumatoid Arthritis

This trial will test whether LY4298445 is safe and well tolerated in healthy adults and in people with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA).

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 63 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: Eli Lilly and Company (Industry-sponsored)
• Locations: 7 sites (Brisbane and 6 other locations)
• Trial ID: NCT07276958 on ClinicalTrials.gov

What this trial studies

This is a Phase 1 interventional trial sponsored by Eli Lilly that examines the safety and tolerability of the investigational drug LY4298445 in both healthy volunteers and adults with SLE or RA. Participants will be enrolled at sites in Australia and China and will receive LY4298445 under controlled dosing regimens with regular safety monitoring. The study includes both healthy cohorts and disease cohorts to compare tolerability across populations, and participation can last up to approximately 52 weeks. Key outcomes focus on adverse events, tolerability measures, and pharmacokinetic data to inform later-stage trials.

Who should consider this trial

Good fit: Ideal candidates are adults (healthy volunteers 18–55 years with BMI 18–32 and weight ≥50 kg, or patients 18–75 years with confirmed SLE or adult-onset RA of at least 6 months and BMI 18–35 with weight 45–145 kg).

Not a fit: People under 18, pregnant or breastfeeding individuals, those with severe uncontrolled comorbidities or organ damage, or anyone outside the trial's weight/BMI ranges are unlikely to benefit from participation.

Why it matters

Potential benefit: If safe and tolerable dosing is identified, this could enable larger trials that might eventually lead to a new treatment option for people with SLE or RA.

How similar studies have performed: Other early-phase trials of immune-modulating agents in SLE and RA have shown mixed signals of promise, but LY4298445 is at an early stage and remains largely untested in patient populations.

Eligibility criteria

Inclusion Criteria: Healthy Participants

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).

Exclusion Criteria:

* 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

Where this trial is running

Brisbane and 6 other locations

• Nucleus Network — Brisbane, Australia (Recruiting)
• Nucleus Network — Melbourne, Australia (Recruiting)
• Peking University First Hospital — Beijing, China (Not_yet_recruiting)
• Peking University Third Hospital — Beijing, China (Not_yet_recruiting)
• Xiangya Hospital of Central South University — Changsha, China (Not_yet_recruiting)
• Renji Hospital, Shanghai Jiaotong University School of Medicine — Shanghai, China (Not_yet_recruiting)
• Union Hospital Tongji Medical College Huazhong University of Science and Technology — Wuhan, China (Not_yet_recruiting)

Study contacts

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

Conditions Healthy; Systemic Lupus Erythematosus; Rheumatoid Arthritis