An Open-label, Phase I Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD5492 Following Single-ascending Dose and Step-up Dose Administration to Adult Participants With Systemic Lupus Erythematosus or Idiopathic Inflammatory Myopathies or Rheumatoid Arthritis

AstraZeneca38 个研究点分布在 10 个国家目标入组 72 人开始时间: 2025年5月1日最近更新: 2026年9月15日

适应症

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方: AstraZeneca
入组人数: 72
试验地点: 38
主要终点: Safety evaluation of AZD5492: Number of participants with treatment-emergent adverse events.

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of this study is to measure the safety, tolerability, PK, and PD of AZD5492 administered subcutaneously in adult participants with SLE or IIM or RA

Study details include:

• The study duration will be a minimum of 180 days in addition to the screening period.

Additional follow-up visits may be required up to 12 months from study start.

• Depending on the study part they are assigned to, participants will be administered AZD5492 once (Part 1), twice (Part 2a), or three times (Part 2b).

详细描述

This is an open-label, multi-centre Phase I study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AZD5492 in adult participants with either SLE or IIM or RA.

The study consists of 2 parts:

Part 1 - Single ascending dose (SAD) Part 1 will be a sequential SAD design in adult participants with SLE. Up to 5 dose levels of AZD5492 are planned to be investigated. Depending on emerging data, up to 4 additional dose levels may be added at the discretion of the Sponsor.

The decision to open Part 2 will be made by the Safety Review Committee (SRC) based on the evaluation of all available data including safety, tolerability, PK, and PD from Part 1 and pertinent data arising from other ongoing studies with AZD5492 will also be considered, and the dose levels and dosing strategy for Part 2 will be confirmed.

After a screening period of up to 42 days, participants will receive 1 dose of AZD5492 and be followed up for at least 179 days post-dose.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Sequential
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 70 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Participant must be 18 to 70 years of age inclusive, at the time of signing the informed consent.
•Diagnosis of SLE:
•Diagnosis of SLE according to the 2019 EULAR/ACR classification criteria for SLE
•Positive for one or more of: anti-nuclear antibodies (titre ≥ 1:80), anti-dsDNA or anti-Sm at screening.
•Active, moderate-severe disease at screening, defined as clinical SLEDAI-2K ≥
•Intolerance to, or inadequate response following at least 3 months of use to, ≥ 3 available treatments, such as the following: corticosteroids, anti-malarial drugs, calcineurin inhibitor, methotrexate, azathioprine, leflunomide, mycophenolic acid or its derivatives, cyclophosphamide, belimumab, anifrolumab, telitacicept, or B-cell depleting monoclonal antibodies.
•Diagnosis of IIM:
•Must have "probable" or "definite" diagnosis of PM or DM (excluding IBM and cancer associated myositis) according to the 2017 EULAR/ACR classification criteria for adult myositis.
•Positive for ≥ 1 disease-specific autoantibody at screening.
•MMT-8 score of ≤ 142/150 and/or CDASI-A ≥ 6
•Fulfill at least one of the following criteria of active disease at screening:
•(i) One or more muscle enzyme elevation (CK, AST, ALT, aldolase, LDH) ≥ 1.3 × ULN (ii) If criterion 3(d)(i) is not met, then at least one of the following criteria must be met: a. Report from MRI performed within 3 months prior to screening with evidence of muscle inflammation b. Report from muscle biopsy performed within 3 months prior to screening that demonstrates active inflammation c. Report from electromyography performed within 3 months prior to screening that exhibits irritable myopathic pattern.
•(e) Intolerance or inadequate response to corticosteroids and ≥2 other SoC treatments, used for at least 3 months each, for which at least one must be a biologic SoC, immunoglobulin or cyclophosphamide.
•Diagnosis of RA:
•(a) Diagnosis of RA as defined by the 2010 EULAR/ACR classification criteria (b) Positive for ≥ 1 disease-specific autoantibody performed by the central laboratory at screening: RF or ACPA (c) Moderate or severe disease activity defined as: (i) ≥6 tender joints and ≥6 swollen joints AND (ii) DAS28-CRP >3.
•(d) Intolerance to or inadequate response following approximately 3 month's treatment or longer to ≥2 b/tsDMARDs (with different mechanisms of action) after failing csDMARD therapy (unless csDMARD therapy is contraindicated). There is no minimum duration for taking a treatment in cases of intolerance.

排除标准

•Any complications of the disease under study which are judged by the investigator to be life or organ threatening or to require treatments which are not permitted in the protocol, including but not limited to:
•Active severe SLE-driven renal disease.
•History of, or current diagnosis of, catastrophic or severe APS (for example diagnosis of an arterial or central/pulmonary venous clot) within 1 year prior to signing the ICF.
•Rapidly progressive and/or severe ILD or ILD that requires oxygen supplementation/therapy (of any type).
•Inclusion Body Myositis or cancer associated myositis.
•Active severe, unstable or history of neuropsychiatric SLE.
•IIM: Pulmonary function tests at screening (or within one month of screening, provided participant confirms no change in respiratory symptoms in the interim) which meet any of the following criteria:
•FVC ≤60% of predicted
•DLCO ≤70% of predicted
•Deterioration in either FVC or DLCO at screening compared to pulmonary function tests performed ≥3 months previously.
•Significant history of or at risk of severe infections.
•Participants with HIV infection.
•Participants with evidence of chronic or active hepatitis B defined as HBsAg positive or HBcAB positive
•Participants with evidence of chronic or active hepatitis C
•Participants with positive COVID-19 PCR.
•Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection.
•Significant CNS pathology.
•Receipt of B-cell-depleting therapy including CD19 or CD20 directed monoclonal antibodies (including but not limited to, ocrelizumab, ofatumumab, obinutuzumab, or rituximab) <3 months prior to Day 1.

研究组 & 干预措施

Part 2: Step-Up Dosing with AZD5492

Experimental

Participants will receive AZD5492 by SC as either:

Part 2a (sSUD): a priming dose on Day 1 followed by a target dose on Day 8; or
Part 2b (dSUD): a priming dose on Day 1, a second priming dose on Day 8, and a target dose on Day 15.

干预措施: AZD5492 (Drug)

Part 1: Single Ascending Dose with AZD5492

Experimental

Participants will receive AZD5492 at an assigned dose as subcutaneous (SC) injection on Day 1.

干预措施: AZD5492 (Drug)