CTRI/2019/10/021809招募中2 期
A randomized, treatment open-label, dose-blinded parallelgroup, three arm, proof-of-concept clinical trial toinvestigate the efficacy and safety of LNP023 comparedwith rituximab in the treatment of subjects with idiopathic membranous nephropathy
Novartis Healthcare Pvt Ltd5 个研究点 分布在 1 个国家目标入组 72 人开始时间: 2019年10月31日最近更新:
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 72
- 试验地点
- 5
- 主要终点
- All arms: To assess the efficacy of the LNP023 regimen B compared with rituximab
研究概览
简要总结
The purpose of this study is to ascertain the efficacy, safety, tolerability and pharmacokinetics of LNP023 over a 24-week treatment period compared with rituximab in subjects with idiopathic membranous nephropathy (MN). The primary end point of the study will be the ratio between baseline Urine Protein Creatinine Ratio (UPCR) and UPCR at 24 weeks of treatment (from 24h urine collection). The study will target subjects with idiopathic MN at high risk of disease progression, on the basis of anti-PLA2R antibody titre and high grade proteinuria.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Written informed consent must be obtained before any study assessment is performed.
- •Able to communicate well with the investigator, to understand and comply with the requirements of the study.
- •Female or male adult (more than or equal to 18 years) subjects at screening visit with a diagnosis of idiopathic (primary) MN confirmed by renal biopsy within 24 months prior to screening.
- •A renal biopsy may be taken at any time during the run-in period to confirm the diagnosis of MN and facilitate subject eligibility, if the most recent biopsy was performed greater than 24 months prior to the screening visit.
- •Anti-PLA2R antibody titer of more than or equal to 100 RU/mL at screening visit (based on the EuroImmun ELISA test).
- •Less than or equal to 50% reduction in both anti-PLA2R level and 24h urine protein between first measurement at screening or run-in visit and baseline.
- •Urine protein more than or equal to 3.5 g per 24h at run-in and baseline visits.
- •Estimated GFR (using the CKD-EPI formula)more than or equal to 45 mL per min per 1.73 m2 at screening visit.
- •Weight of at least 35 kg and body mass index (BMI) of at least 15 kg per m
- •Receiving stable dose at the maximum recommended dose according to local guidelines or maximum tolerated dose of ACEi and/or ARB and/or statins and/or diuretics.
- •The dose of ACEi or ARB must be stable for at least 8 weeks prior to Day 1, defined as <25% dose change over this 8 week period.
- •Vaccination against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae (in accordance with local guidelines) at least 28 days prior to Day 1 and no longer than 5 years prior to Day
- •Subject agrees to collect 24h urine sample at home and to bring it to the investigational site at specific visits.
排除标准
- •Secondary causes of MN, e.g. systemic autoimmune diseases, solid or haematological malignancies, infections or chronic intake of drugs (e.g. gold salts, NSAIDs, penicillamines)
- •Diagnostic renal biopsy showing evidence of crescent formation in glomeruli, suggestive of an alternative or additional diagnosis to primary idiopathic MN.
- •Previous treatment with B-cell depleting or B-cell modifying agents such as, but not limited to rituximab, belimumab, daratumomab or bortezomib.
- •Previous treatment with immunosuppressive agents such as cyclophosphamide, chlorambucil, mycophenolate mofetil (or equivalent), cyclosporine, tacrolimus or azathioprine within 90 days prior to Day
- •Low dose systemic corticosteroid therapy is permitted, though the subject should have been on stable dose equivalent to less than or equal to 10 mg prednisolone for at least 90 days prior to Day 1
- •Administration of any live vaccination within 4 weeks prior to Day 1
- •Previous treatment with gemfibrozil or strong CYP2C8 inhibitors such as clopidogrel within 7 days prior to Day 1
- •Use of other investigational drugs within 30 days (e.g. small molecules) or 5 half-lives of screening or until the expected pharmacodynamic effect has returned to baseline (e.g. biologics), whichever is longer; or longer if required by local regulations
- •History of malignancy of any organ system (other than localised basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years prior to screening start, regardless of whether there is evidence of local recurrence or metastases
- •History of clinically significant ECG abnormalities, or any of the following ECG abnormalities at screening or baseline visit: a.
- •QTcF more than 450 msec (males) b.
- •QTcF more than 460 msec (females) History of familial long QT syndrome or known family history of Torsades de Pointes Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of the study
- •Presence or suspicion (based on judgment of the investigator) of active infection within 30 days prior to Day 1, or history of severe recurrent bacterial infections
- •Pregnancy or nursing (lactation), where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human Chrorionic Gonadotropin (hCG) laboratory test
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using basic contraception during dosing and for 1 week after stopping of LNP023 or for 12 months after stopping rituximab.
- •Basic contraception methods include: a.
- •Barrier methods of contraception: Condom or Occlusive cap.
结局指标
主要结局
All arms: To assess the efficacy of the LNP023 regimen B compared with rituximab
时间窗: Ratio between baseline UPCR and UPCR at 24 weeks of treatment (from 24h urine collection)
次要结局
- LNP023 arms: To assess the safety and tolerability of regimen A and regimen B of LNP023(ECG parameters, vital signs, safety laboratory data, physical exam and collection of AEs assessed from baseline until the end of the study visit.)
- LNP023 arms: To assess the relationship between LNP023 systemic drug exposure and pharmacodynamics, mode-of-action markers and clinical efficacy(a. Plasma levels of Bb and sC5b-9)
- LNP023 arms: To assess the difference in response between the low (regimen A) and high (regimen B) dose of LNP023(Ratio between baseline UPCR and UPCR at 24 weeks of treatment (from 24h urine collection))
- All arms: To assess the effect of LNP023 compared with rituximab on proteinuria remission and renal function(a. Proportion of subjects with a complete remission, defined as proteinuria less than or equal to 0.3 g per day at 24 weeks of treatment, derived from 24h urine collection)
- LNP023 arms: To assess the(pharmacokinetics of LNP023)
研究者
研究点 (5)
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