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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат LY4298445
  Administered SC
• Препарат LY4298445
  Administered IV

Первичные конечные точки

• Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration [Срок оценки: Baseline up to Week 52]

Вторичные конечные точки (3)

• Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY4298445 [Срок оценки: Baseline up to Approximately Week 57]
• PK: Maximum Concentration (Cmax) of LY4298445 [Срок оценки: Baseline up to Week 52]
• Pharmacodynamic (PD): Degree of Peripheral B Cell Depletion Following Biopsy in Participants [Срок оценки: Baseline up to Week 52]

Критерии участия

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).

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Фундаментальное исследование

Центры проведения

Китай · 7 центров

• Peking University First Hospital — Пекин
• Peking University Third Hospital — Пекин
• Xiangya Hospital of Central South University — Чанша
• Anhui Provincial Hospital — Хэфэй
• Renji Hospital, Shanghai Jiaotong University School of Medicine — Шанхай
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou
• Union Hospital Tongji Medical College Huazhong University of Science and Technology — Ухань

Австралия · 2 центра

• Nucleus Network — Brisbane
• Nucleus Network — Melbourne

Идентификаторы

NCT: NCT07276958 · 27747 · J6S-MC-KCAA

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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