A Phase II, Randomized, Double-blind, Placebo-controlled, Multicenter Study Evaluating Efficacy, Safety, and Pharmacokinetics of Crovalimab in Patients With Antiphospholipid Syndrome (APS)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 300
- 主要终点
- Time From Randomization to First Occurrence of Objectively Confirmed Arterial Thrombosis, Venous Thromboembolism or Cardiovascular Death
研究概览
简要总结
The main purpose of this study is to evaluate the efficacy of crovalimab compared with placebo as an add-on therapy to vitamin K antagonist (VKA) in participants with APS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age ≥18 years and ≤70 years, and body weight ≥40 kilograms (kg), at the time of signing Informed Consent Form
- •Vaccination against N. meningitidis, H. influenzae type B, and S. pneumoniae
- •Participants classified with APS who have experienced at least two prior arterial and/or venous thrombotic events, based on the 2023 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) criteria, positive for at least two of the following: lupus anticoagulant (LAC) test, anticardiolipin antibodies (aCL), anti-β2-glycoprotein 1 antibodies (aβ2GP1)
- •Participants receiving corticosteroids, antimalarial treatment, non-biologic disease-modifying rheumatic drugs, statins, and low dose aspirin must be on a stable dose prior to the first dose of study treatment
- •Willingness and ability to comply with a VKA regimen titrated to a therapeutic target internal normalized ratio (INR)
- •Agreement to adhere to the contraception requirements
排除标准
- •Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the time frame in which contraception is required
- •Treatment with investigational therapy, complement inhibitor, and/or other immune-suppressive biologic therapy within 5 half-lives of that agent prior to screening visit, or plans to participate in another investigational trial
- •Presence of another systemic autoimmune disease that is unstable and requires additional treatment, and constitutes the principal illness and may impact evaluation of the concurrent APS
- •Inadequate renal and hepatic function
- •Uncontrolled hyperlipidemia and/or hypertension, known diabetes mellitus, and/or serious infection requiring hospitalization or antibiotics prior to Week 1 Day 1
- •History or condition associated with increased bleeding risk
研究组 & 干预措施
Crovalimab + VKA
Participants will receive 3 loading doses of crovalimab, 680 milligrams (mg) or 1020 mg, as a subcutaneous (SC) injection based on their body weight (BW) at Weeks 1, 2 and 3 followed by maintenance doses, every 4 weeks (Q4W) from Week 5 until arterial thrombosis, venous thromboembolism or cardiovascular death. Participants will also receive VKA with a target internal normalized ratio (INR) based on investigator's discretion and local guidance.
干预措施: Crovalimab (Drug)
Crovalimab + VKA
Participants will receive 3 loading doses of crovalimab, 680 milligrams (mg) or 1020 mg, as a subcutaneous (SC) injection based on their body weight (BW) at Weeks 1, 2 and 3 followed by maintenance doses, every 4 weeks (Q4W) from Week 5 until arterial thrombosis, venous thromboembolism or cardiovascular death. Participants will also receive VKA with a target internal normalized ratio (INR) based on investigator's discretion and local guidance.
干预措施: VKA (Drug)
Placebo + VKA
Participants will receive 3 doses of placebo as a SC injection with equal volume dosing as the weight-based crovalimab at Weeks 1, 2, and 3, followed by Q4W doses, as a SC injection, from Week 5 until arterial thrombosis, venous thromboembolism, or cardiovascular death. Participants will also receive VKA with a target INR based on the investigator's discretion and local guidance.
干预措施: Placebo (Drug)
Placebo + VKA
Participants will receive 3 doses of placebo as a SC injection with equal volume dosing as the weight-based crovalimab at Weeks 1, 2, and 3, followed by Q4W doses, as a SC injection, from Week 5 until arterial thrombosis, venous thromboembolism, or cardiovascular death. Participants will also receive VKA with a target INR based on the investigator's discretion and local guidance.
干预措施: VKA (Drug)
结局指标
主要结局
Time From Randomization to First Occurrence of Objectively Confirmed Arterial Thrombosis, Venous Thromboembolism or Cardiovascular Death
时间窗: Up to approximately 4.5 years
次要结局
- Time From Randomization to the First Occurrence of Objectively Confirmed Venous Thromboembolism(Up to approximately 4.5 years)
- Time From Randomization to the First Occurrence of Objectively Confirmed Arterial Thrombosis(Up to approximately 4.5 years)
- Percentage of Participants With Adverse Events (AEs) With Severity Determined According to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0)(Up to approximately 4.5 years)
- Percentage of Participants With Injection Site Reactions and Hypersensitivity(Up to approximately 4.5 years)
- Percentage of Participants With Infections and Severity of Infection(Up to approximately 4.5 years)
- Percentage of Participants With AEs Leading to Study Drug Discontinuation(Up to approximately 4.5 years)
- Serum Concentrations of Crovalimab Over Time(Up to approximately 4.5 years)