A Phase 2, Double-Blind, Placebo-Controlled Trial of Mycophenolate Mofetil Alone or With Voclosporin for Systemic Lupus: Examining Distinct Immunophenotypes to Validate and Enhance Rational Treatment (DIVERT) (ALE10)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 10
- 主要终点
- The Percentage of Participants Who Experience a Stage 2 Treatment Failure at or Before the Stage 2 Week 24 Visit.
研究概览
简要总结
The primary purpose of this study is to evaluate the potential effectiveness of 24 weeks of MMF within previously discovered immunologically defined subsets of SLE patients. Treatment effects will be evaluated within the individual immunologically-homogenous subsets defined at screening. This study will also explore and compare pre-randomization gene expression patterns among responders and non-responders to MMF and MMF plus voclosporin, use comprehensive immunophenotyping to study the immunologic changes that accompany treatment- induced disease improvement and to better understand immunologic changes associated with the loss of clinical response.
详细描述
The study was conducted in 3 stages with a maximum participant follow-up time of 56 weeks. Stage 1 was a treatment withdrawal period lasting up to 4 weeks where consenting participants receive up to 3 intramuscular injections of a long-acting corticosteroid to achieve amelioration of symptoms. In addition, participants withdraw from all other treatments for lupus with the following exceptions:
(i) as needed (PRN) nonsteroidal anti-inflammatory treatments may be started or continued, (ii) PRN topicals may be continued, (iii) hydroxychloroquine, chloroquine, or quinacrine may be continued at any stable dose, and (iv) prednisone, if<= 10 mg/day, may be continued at stable doses but not started.
Qualifying participants from Stage 1 were randomized (1:1) into Stage 2 to receive either MMF or placebo for MMF for up to 48 weeks. Participants who experienced a Stage 2 treatment failure at or before the Week 24 visit and a corticosteroid injection was deemed sufficient for treatment without new or increased lupus medication were eligible to re-randomize (1:1) into Stage 3 to receive either MMF + Voclosporin or MMF + Placebo for Voclosporin for up to 24 Weeks.
Participants who did not experience a Stage 2 treatment failure at or before the Stage 2 Week 48 visit were to return for an End of Study/Safety Follow-up visit 4 weeks after the final dose of study-provided medication. Similarly, participants who did not experience a Stage 3 treatment failure at or before the Stage 3 Week 24 visits were asked to return for an End of Study/Safety Follow-up visit 4 weeks after the final dose of study provided medication.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
MMF
Participants will receive 500 mg mycophenolate mofetil (MMF) bid for 7 days, followed by 500mg and 1,000mg MMF in divided doses for 7 days. They will then continue at a stable dose of 1,000mg MMF bid. Visits to evaluate AEs, vital signs, hematology and chemistry, study medication compliance, medication use, disease status, participant reported outcomes, and to obtain biomarker samples will occur every 4 weeks after randomization
干预措施: Mycophenolate Mofetil (Drug)
Placebo for MMF
Participants will receive 500 mg corresponding mycophenolate mofetil (MMF) placebo bid for 7 days, followed by 500mg and 1,000mg corresponding MMF placebo in divided doses for 7 days. They will then continue at a stable dose of 1,000mg corresponding MMF placebo bid. Visits to evaluate AEs, vital signs, hematology and chemistry, study medication compliance, medication use, disease status, participant reported outcomes, and to obtain biomarker samples will occur every 4 weeks after randomization
干预措施: Placebo for Mycophenolate Mofetil (Drug)
MMF+ Placebo for Voclosporin
Participants randomized in this arm will receive up to 24 weeks of mycophenolate mofetil (MMF) plus placebo for voclosporin, also during the first 2 weeks of treatment, a single intramuscular injection of a long-acting corticosteroid may be administered if needed to achieve amelioration of symptoms without meeting the definition of treatment failure in Stage 3 and without a requirement to stop Stage 3 study-provided medication
干预措施: Placebo for Voclosporin (Drug)
MMF+ Placebo for Voclosporin
Participants randomized in this arm will receive up to 24 weeks of mycophenolate mofetil (MMF) plus placebo for voclosporin, also during the first 2 weeks of treatment, a single intramuscular injection of a long-acting corticosteroid may be administered if needed to achieve amelioration of symptoms without meeting the definition of treatment failure in Stage 3 and without a requirement to stop Stage 3 study-provided medication
干预措施: Mycophenolate Mofetil (Drug)
MMF+ Voclosporin
Participants randomized in this arm will receive up to 24 weeks of mycophenolate mofetil (MMF) plus voclosporin, also during the first 2 weeks of treatment, a single intramuscular injection of a long-acting corticosteroid may be administered if needed to achieve amelioration of symptoms without meeting the definition of treatment failure in Stage 3 and without a requirement to stop Stage 3 study-provided medication
干预措施: Voclosporin (Drug)
MMF+ Voclosporin
Participants randomized in this arm will receive up to 24 weeks of mycophenolate mofetil (MMF) plus voclosporin, also during the first 2 weeks of treatment, a single intramuscular injection of a long-acting corticosteroid may be administered if needed to achieve amelioration of symptoms without meeting the definition of treatment failure in Stage 3 and without a requirement to stop Stage 3 study-provided medication
干预措施: Mycophenolate Mofetil (Drug)
结局指标
主要结局
The Percentage of Participants Who Experience a Stage 2 Treatment Failure at or Before the Stage 2 Week 24 Visit.
时间窗: From Baseline to Stage 2 Week 24
Treatment failure is defined as the first occurrence after randomization (Stage 2) of any of the following events: 1. Methylprednisolone acetate injection or treatment with a new or increased lupus medication, except the occasional use of corticosteroids for reasons not associated with Systemic Lupus Erythematosus (SLE) flare 2. British Isles Lupus Assessment Group (BILAG) flare, defined as any item marked new or worse that could support a BILAG A (severe flare) or 2 organs with items marked new or worse that could support a BILAG B (moderate flare), and if the participant's condition is deemed by the investigator to be "moderately worse" or "much worse" compared to the day of randomization, as assessed by the Clinician Global Impression of Change (CGI-C) 3. Premature permanent discontinuation of study-assigned treatment for any reason
次要结局
- Clinical Response in Stage 2, Defined by the BILAG-based Combined Lupus Assessment (BICLA) at Stage 2 Week 24.(Stage 2 Week 24)
- The Proportion of Participants Who Experience a Stage 3 Treatment Failure, After Stage 3 Re-randomization at or Before Completing Stage 3 Week 24.(From re-randomization to Stage 3 Week 24)
- Time to Treatment Failure in Stage 3, Defined as the Interval From the Day of Stage 3 Randomization Until the Day of Treatment Failure.(Start of Stage 3 up to the day of treatment failure)
- Clinical Response in Stage 3, Defined by the BILAG-based Combined Lupus Assessment (BICLA) at Stage 3 Week 24.(Stage 3 Week 24)
- The Incidence of Grade 3 or Higher Related Adverse Events (AEs) in Stage 2(Stage 2 Day 0 up to Stage 2 Week 48)
- The Incidence of Grade 3 or Higher Infections in Stage 2(Stage 2 Day 0 up to Stage 2 Week 48)
- The Incidence of Grade 3 or Higher Related Adverse Events (AEs) in Stage 3(After Stage 3 re-randomization Day 0 to Stage 3 Week 24)
- The Incidence of Renal Dysfunction in Stage 1(Day -28 to Day -1)
- The Incidence of Grade 3 or Higher Hypertension in Stage 2(Stage 2 Day 0 up to Stage 2 Week 48)
- The Incidence of Grade 3 or Higher Hypertension in Stage 3(After Stage 3 re-randomization Day 0 to Stage 3 Week 24)
- The Incidence of Grade 3 or Higher Infections in Stage 1(Day -28 to Day -1)
- The Incidence of Grade 3 or Higher Infections in Stage 3(After Stage 3 re-randomization Day 0 to Stage 3 Week 24)
- The Incidence of Renal Dysfunction in Stage 2(Stage 2 Day 0 up to Stage 2 Week 48)
- The Incidence of Renal Dysfunction in Stage 3(After Stage 3 re-randomization Day 0 to Stage 3 Week 24)
- The Incidence of Grade 3 or Higher Hypertension in Stage 1(Day -28 to Day -1)