An Adaptive, Randomized, Double-blind, Dose Exploration, Parallel Group, Placebo Controlled, Multicenter Phase 2 Trial to Evaluate the Efficacy, Safety and Tolerability of LNP023 in Combination With Standard-of-care With and Without Oral Corticosteroids in Patients With Active Lupus Nephritis Class III-IV, +/- V
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 240
- 试验地点
- 124
- 主要终点
- Part 1 and 2: Proportion of patients achieving Complete Renal Response (CRR) at week 24 in the absence of renal flares
研究概览
简要总结
The overall purpose of this two-part study is to evaluate the efficacy, safety and tolerability of iptacopan (LNP023) in addition to standard of care treatment.
详细描述
The overall purpose of this two-part study is to evaluate the efficacy, safety and tolerability of iptacopan (LNP023) in addition to standard of care treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Unequivocally positive ANA test result and/or a positive anti dsDNA at screening Active biopsy-proven lupus nephritis within 3 months of screening demonstrating Class III or IV lupus nephritis with or without co-existing features of Class V lupus nephritis.
- •Documentation of active renal disease at the time of screening necessitating the commencement of therapy with corticosteroids in combination with MMF/MPS.
- •eGFR ≥ 30 ml/min/1.73 m2 Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infections Vaccination against Haemophilus influenzae infection Supportive care including stable dose regimen of anti-malarials (e.g. hydroxychloroquine) unless contraindicated, ACEi or ARB at either locally approved maximal daily dose or the maximally tolerated dose (per investigators' judgement) at screening, as per the local clinical practice. Doses should remain stable throughout the study.
- •First presentation or flare of lupus nephritis.
排除标准
- •Induction treatment with cyclophosphamide within 3 months of planned treatment for this study; treatment with calcineurin inhibitors within the previous 3 months prior to randomization.
- •Presence of rapidly progressive glomerulonephritis (RPGN) as defined by 50% decline in eGFR within 3 months prior to screening.
- •Renal biopsy presenting with interstitial fibrosis/tubular atrophy (IF/TA) or glomerulosclerosis of more than 50%, or which in the opinion of the investigator is such that it precludes likely response to immunosuppressive therapy.
- •Participants being treated with systemic corticosteroids (>5 mg/day prednisone or equivalent) for indications other than SLE or LN e.g. acute asthma, inflammatory bowel disease.
- •Participants being treated with systemic corticosteroids for SLE or LN will be excluded if they have taken more than an average of 15 mg/day prednisone (or equivalent) in the previous 4 weeks and more than an average of 30 mg/day in the previous 1 week Receipt of more than a total dose of 1000 mg equivalent i.v. pulse methylprednisolone (cumulative dose) within 2 weeks prior to enrollment (and at enrollment)
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Placebo matching iptacopan + standard of care (part 2)
Placebo matching iptacopan + standard of care
干预措施: Placebo + standard of care (Drug)
Iptacopan + standard of care (part 1)
Iptacopan + standard of care
干预措施: Iptacopan (part 1) (Drug)
Iptacopan + standard of care (part 2)
Iptacopan + standard of care
干预措施: Iptacopan (part 2) (Drug)
Placebo matching iptacopan + standard of care (part 1)
Placebo matching iptacopan standard of care
干预措施: Placebo + standard of care (Drug)
Iptacopan + placebo (part 2)
Iptacopan + placebo standard of care
干预措施: Iptacopan + placebo (Drug)
结局指标
主要结局
Part 1 and 2: Proportion of patients achieving Complete Renal Response (CRR) at week 24 in the absence of renal flares
时间窗: Baseline and week 24
Part 1: To evaluate the proportion of patients achieving complete renal response with iptacopan treatment "A" plus standard of care, compared to treatment alone Part 2: To evaluate the proportion of patients achieving complete renal response with Iptacopan treatment "B" plus standard of care, compared to treatment "D" alone Part 2: To evaluate the proportion of patients achieving complete renal response with Iptacopan treatment "C" plus standard of care, compared to treatment "D" alone Complete Renal Response is defined as meeting the following criteria: estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2 or no less than 85% of baseline value, and 24h urine protein-to-creatinine ratio (UPCR) ≤ 0.5 g/g.
次要结局
- Time-to-Complete Renal Response (CRR) based on first morning void(FMV) urine samples(Week 24 and Week 52)
- Change from baseline in SLEDAI-2K score at weeks 24 and 52(Weeks 24 and 52)
- Parts 1 and 2: Proportion of patients achieving CRR or PRR in the absence of renal flares(Baseline, week 24, week 52)
- Log-transformed ratio to baseline of 24h UPCR at week 24(Baseline week 24)
- Change from baseline in BILAG-2004 score at weeks 24 and 52(Weeks 24 and 52)
- Change from baseline FACIT-Fatigue Score(Weeks 24 and 52)
- Proportion of patients achieving ≥25% UPCR reduction in the absence of renal flares compared to baseline at week 24(Baseline, week 24 week 52)