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
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Eli Lilly and Company
- Enrollment
- 63
- Locations
- 7
- Primary Endpoint
- Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Single (Participant)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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.
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 -
- •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)
- •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
Arms & Interventions
LY4298445 (Part A1)
Single-ascending dose (SAD) of LY4298445 administered subcutaneously (SC) or intravenously (IV) in healthy participants
Intervention: LY4298445 (Drug)
LY4298445 Placebo (Part A1)
SAD of LY4298445 administered SC or IV in healthy participants
Intervention: LY4298445 (Drug)
LY4298445 (Part A2)
SAD of LY4298445 administered SC in participants with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA)
Intervention: LY4298445 (Drug)
LY4298445 (Part B)
Multiple-ascending doses (MAD) of LY4298445 administered SC in participants with SLE or RA
Intervention: LY4298445 (Drug)
LY4298445 (Part C)
Single dose of LY4298445 administered SC in healthy Japanese and Chinese participants
Intervention: LY4298445 (Drug)
LY4298445 Placebo (Part C)
Single dose of LY4298445 administered SC in healthy Japanese and Chinese participants
Intervention: LY4298445 (Drug)
Outcomes
Primary Outcomes
Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Time Frame: Baseline up to Week 52
A summary of SAEs regardless of causality, will be reported in the Reported Adverse Events module
Secondary Outcomes
- 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)