A Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-response Study to Investigate the Biological Activity, Safety, Tolerability, and Pharmacokinetics of ACT-334441 in Subjects With Systemic Lupus Erythematosus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 19
- 主要终点
- Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT)
研究概览
简要总结
International trial to evaluate the biological activity and safety of cenerimod (ACT-334441) in systemic lupus erythematosus (SLE) patients.
详细描述
This multicentre, double-blind, placebo-controlled study will have a staggered approach (Part A and B).
In part A, eligible patients will be randomly assigned (1:1:1:1) to once daily oral administration of cenerimod (0.5, 1, 2 mg) or placebo. After all patients have completed 4 weeks of treatment during part A, an Independent Data Monitoring Committee will review non-blinded data in an interim analysis to evaluate the safety profile of cenerimod and recommend whether the study could proceed to part B.
In part B, additional patients will be randomized (3:1) to once daily oral administration of cenerimod 4 mg or placebo.
All participants will receive study medication for 12 weeks.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female participants aged 18 to 65 years with established SLE. Participants must have active SLE, Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) score of at least 2 points for musculoskeletal or mucocutaneous manifestations and history or presence at screening of positive anti-nuclear antibodies (ANA) or anti-double-stranded DNA (anti-dsDNA) antibodies.
- •Enrolled participants must be treated with background SLE medications.
排除标准
- •Participants with significant medical conditions or therapies for such conditions (e.g., cardiovascular, pulmonary, immunological, hepatic, ophthalmological, infection and infection risks, history or presence of malignancy, history or presence of bone marrow or solid organ transplantation) or lactating or pregnant women.
- •Participants with severe SLE disease or with clinically relevant medical or surgical conditions that, in the opinion of the investigator, would put the subject at risk by participating in the study.
研究组 & 干预措施
Matching placebo (Part A and B)
Capsules of matching placebo taken orally once daily for 12 weeks.
干预措施: Matching placebo (Drug)
Cenerimod 2 mg (Part A)
Participants will receive cenerimod 2 mg capsules orally once daily for 12 weeks.
干预措施: Cenerimod (Drug)
Cenerimod 0.5 mg (Part A)
Participants will receive cenerimod 0.5 mg capsules orally once daily for 12 weeks.
干预措施: Cenerimod (Drug)
Cenerimod 1 mg (Part A)
Participants will receive cenerimod 1 mg capsules orally once daily for 12 weeks.
干预措施: Cenerimod (Drug)
Cenerimod 4 mg (Part B)
Participants will received cenerimod 4 mg capsules orally once daily for 12 weeks. This treatment arm will start after all patients in Part A have completed 4 weeks of placebo, 0.5 mg, 1 mg and 2 mg cenerimod treatment.
干预措施: Cenerimod (Drug)
结局指标
主要结局
Change in Total Lymphocyte Count From Baseline to End-of-treatment (EOT)
时间窗: Baseline to end-of-treatment (EOT) (up to 12 weeks)
The primary objective of the clinical study was to asses whether cenerimod could reduce the number of circulating lymphocytes in the bloodstream of people with systemic lupus erythematosus (SLE). The change was defined as: Total lymphocyte count at end-of-treatment (EOT) minus total lymphocyte count at baseline. A negative change over time indicates that the number of peripheral circulating lymphocytes has decreased. The reduction of the total lymphocyte count over a treatment period indicates a pharmacodynamic effect. The value at baseline was defined as the last non-missing value obtained from a sample taken prior to the first study treatment intake. End-of-treatment (EOT) was defined as the last post-baseline value with treatment for at least 21 days up to Week 12.
Change in Total Lymphocyte Count From Baseline to Each Post-baseline Assessment
时间窗: Baseline, Week 2, Week 4, Week 8, Week 12, end-of-treatment Visit (up to 12 weeks)
The primary objective of the clinical study was to assess whether cenerimod could reduce the number of circulating lymphocytes in the bloodstream of people with systemic lupus erythematosus (SLE). The change was defined as: Total lymphocyte count at visit minus total lymphocyte count at baseline. A negative change over time indicates that the number of peripheral circulating lymphocytes has decreased. The reduction of the total lymphocyte count over a treatment period indicates a pharmacodynamic effect. The value at baseline was defined as the last non-missing value obtained from a sample taken prior to the first study treatment intake. End-of-treatment (EOT) was defined as the last post-baseline value with treatment for at least 21 days up to Week 12.
次要结局
未报告次要终点