A Two-year, Phase III Randomized, Double-blind, Parallel-group, Placebo-controlled Trial to Evaluate the Safety, Efficacy, and Tolerability of 300 mg s.c. Secukinumab Versus Placebo, in Combination With SoC Therapy, in Patients With Active Lupus Nephritis
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 275
- 试验地点
- 9
- 主要终点
- Percentage of Participants Achieving Complete Renal Response (CRR) at Week 52
研究概览
简要总结
This was a pivotal, randomized, double-blind, placebo-controlled trial evaluating at Week 52 the efficacy and safety of secukinumab versus placebo in patients with active lupus nephritis (ISN/RPS Class III or IV, with or without co-existing class V features) also receiving background standard of care therapy (SoC).
详细描述
The study consisted of the following parts:
- Screening (up to 42 days/6 weeks)
- Run-in period (optional): For subjects who received Mycophenolic acid (MPA) as SoC induction therapy as per investigator's decision and who were not already on MPA at Screening, MPA dosing was initiated during a run-in period before Randomization (for up to 4 weeks prior to the first dose of secukinumab)
- Treatment Period: Duration of 104 weeks of treatment with secukinumab/placebo in addition to SoC treatment (with last dose given at Week 100)
- Secukinumab dosing was started with initial dosing of 300 mg s.c. injections at Baseline, Weeks 1, 2, 3, and 4, followed by dosing every 4 weeks
- Follow-up period: Duration of 8 weeks (last visit performed 12 weeks after last dose of study medication) for all except for subjects entering extension study CAIN457Q12301E1 (NCT05232864).
A total of 275 subjects were enrolled and were randomized to secukinumab 300 mg (n = 137) or placebo (n = 138) until study termination. Recruitment in this study was stopped on 26-May-2023. The CAIN457Q12301 study was terminated early by Novartis due to futile results from interim analysis 1 (IA1). There was no safety related reasons for early termination or concerns for the subjects in the study. The decision was made to terminate both the core and the related extension study in view of treatment futility of the core study.
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)
盲法说明
double-blind
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older 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
secukinumab
A blinded, weekly, subcutaneous (s.c.) secukinumab 300 mg loading regimen was administered for the first 4 weeks followed by a monthly maintenance dose in all randomized subjects thereafter.
干预措施: secukinumab (Drug)
placebo
A blinded, weekly, subcutaneous (s.c.) matching placebo loading regimen was administered for the first 4 weeks followed by a monthly maintenance dose in all randomized subjects thereafter.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants Achieving Complete Renal Response (CRR) at Week 52
时间窗: Baseline, Week 52
Complete Renal Response (CRR) is a composite endpoint defined as: * Estimated Glomerular Filtration Rate (eGFR) \>= 60 mL/min/1.73 m\^2 or no less than 85% of core Baseline values and * 24-hour Urine-to-Protein Creatinine Ratio (UPCR) =\< 0.5mg/mg * No treatment discontinuation before Week 52 * The subject did not receive more than 10 mg/day prednisone or equivalent for \>= 3 consecutive days or for \>= 7 days in total during Week 44 through Week 52. Non-responder imputation (NRI) was used for participants who did not have the required data to compute responses at Week 52 or who had discontinued study treatment before Week 52. A logistic regression model was used for the analysis of this endpoint.
次要结局
- Change From Baseline in 24-hour Urine Protein-to Creatinine Ratio (UPCR)(Baseline, Week 52)
- Percentage of Participants Achieving Partial Renal Response (PRR) at Week 52(Baseline, Week 52)
- Average Daily Dose of Oral Corticosteroids(Week 16 to Week 52)
- Percentage of Participants Achieving Partial Renal Response (PRR) at Week 24(Baseline, Week 24)
- Incidence Rate of Participants Achieving Complete Renal Response (CRR) up to Week 52(Baseline to Week 52)
- Incidence Rate of Participants Achieving Partial Renal Response (PRR) up to Week 52(Baseline to Week 52)
- Time to Achieve First Morning Void Urine Protein-to-Creatinine Ratio (UPCR) <= 0.5 mg/mg up to Week 52(Baseline to Week 52)
- Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) Mean Change From Baseline up to Week 52(Baseline, Week 12, Week 24, Week 36, Week 52)
- Short Form Health Survey (SF-36) Version 2 (Acute Form) Mean Change From Baseline in Physical Component Score (PCS) up to Week 52(Baseline, Week 12, Week 24, Week 36, Week 52)
- Lupus Quality of Life (LupusQoL) Physical Health Score Mean Change From Baseline up to Week 52(Baseline, Week 12, Week 24, Week 36, Week 52)
- Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs)(From first dose of study treatment up to approximately 2 years)
- Percentage of Participants With Complete Renal Response (CRR) at Week 104 Within Those Who Had Achieved CRR at Week 52 in the Secukinumab Group(Week 52 to Week 104)
- Percentage of Participants With Improved or Maintained Response (PRR or CRR) at Week 104 in Those Who Had Achieved at Least PRR at Week 52 in the Secukinumab Group(Week 52 to Week 104)