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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 68
- 试验地点
- 9
- 主要终点
- Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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 3.
- •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).
排除标准
- •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
研究组 & 干预措施
LY4298445 (Part A1)
Single-ascending dose (SAD) of LY4298445 administered subcutaneously (SC) or intravenously (IV) in healthy participants
干预措施: LY4298445 (Drug)
LY4298445 Placebo (Part A1)
SAD of LY4298445 administered SC or IV in healthy participants
干预措施: LY4298445 (Drug)
LY4298445 (Part A2)
SAD of LY4298445 administered SC in participants with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA)
干预措施: LY4298445 (Drug)
LY4298445 Placebo (Part C)
Single dose of LY4298445 administered SC in healthy Japanese and, optionally, Chinese participants
干预措施: LY4298445 (Drug)
LY4298445 (Part B)
Multiple-ascending doses (MAD) of LY4298445 administered SC in participants with SLE or RA
干预措施: LY4298445 (Drug)
LY4298445 (Part C)
Single dose of LY4298445 administered SC in healthy Japanese and, optionally, Chinese participants
干预措施: LY4298445 (Drug)
结局指标
主要结局
Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
时间窗: Baseline up to Week 52
A summary of SAEs regardless of causality, will be reported in the Reported Adverse Events module
次要结局
- 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)