NCT05679401终止3 期
A Phase 3 Open-label, Controlled, Randomised, Multi-centre Trial Comparing Imlifidase and Standard-of-care With Standard-of-care Alone in the Treatment of Severe Anti-GBM Antibody Disease (Goodpasture Disease)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 50
- 试验地点
- 84
- 主要终点
- Renal function as evaluated by estimated glomerular filtration rate (eGFR) at 6 months
研究概览
简要总结
An open-label, controlled, randomised, multi-centre Phase 3 trial evaluating renal function in patients with severe anti-GBM disease comparing imlifidase and standard of care (SoC) with SoC alone. All patients will remain in the trial for 24 months.
详细描述
After being informed about the study and potential risks, all patients giving written informed consent will undergo screening to determine eligibility for study entry. Patients will be randomised to treatment in a 1:1 ratio to either imlifidase and SoC or SoC only.
SoC consists of a combination of plasma exchange (PLEX), cyclophosphamide (CYC), and glucocorticoids. For patients randomised to the imlifidase arm the first PLEX immediately after randomisation is replaced by administration of imlifidase.
Kidney function, anti-GBM antibody levels, pulmonary symptoms, safety, pharmacokinetic/pharmacodynamic (PK/PD) and health related quality of life (HRQoL) among others, will be assessed.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Anti-GBM antibodies constituting an indication for PLEX as judged by the Investigator
- •Haematuria on dipstick and/or urinary sediment
- •eGFR(MDRD) <20 mL/min/1.73 m^2
- •Patients aged ≥18 years
- •Willing and able to give written Informed Consent and to comply with the requirements of the study protocol
排除标准
- •Diagnosis of anti-GBM disease more than 14 days prior to randomisation
- •Anuria during the last 24-hour
- •Any constituent of SoC given more than 10 days prior to randomisation
- •IVIg within 4 weeks before randomisation
- •History or presence of any medical condition or disease which, in the opinion of the investigator, may place the patient at unacceptable risk, or jeopardise the purpose of the study
- •Patients previously randomised in the study
- •Unsuitable to participate in the trial for any other reason in the opinion of the investigator
- •Pregnancy or breast feeding
- •Contraception:
- •Men who are not vasectomised or abstinent or with a partner (of child-bearing potential) not willing to use one of the highly effective contraceptives listed below from screening to 6 months following discontinuation of CYC
- •Men who are not willing to refrain from donating sperm from screening to 6 months following discontinuation of CYC
- •Men who are not willing to use a condom during any form of sexual intercourse, regardless of a partner being of child-bearing potential from screening to 6 months following discontinuation of CYC
- •Women of child-bearing potential not willing or not able to use at least one highly effective contraceptive method from screening to 12 months following discontinuation of CYC.
- •In the context of this trial, a highly effective method is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly such as:
- •combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral/intravaginal/transdermal)
- •progestogen-only hormonal contraception associated with inhibition of ovulation (oral/injectable/implantable)
- •intrauterine device (IUD)
- •intrauterine hormone-releasing system (IUS)
- •bilateral tubal occlusion
- •vasectomised partner
- •true abstinence: When this is in line with the preferred and usual lifestyle of the patient. [Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception]
- •Previous imlifidase treatment or known hypersensitivity to any of the excipients
研究组 & 干预措施
Imlifidase and Standard-of-Care (SoC)
Experimental
- Imlifidase is administered IV as one dose of 0.50 mg/kg over 30 minutes.
- SoC consists of a standardized combination of PLEX, CYC, and glucocorticoids.
干预措施: Imlifidase (Drug)
Imlifidase and Standard-of-Care (SoC)
Experimental
- Imlifidase is administered IV as one dose of 0.50 mg/kg over 30 minutes.
- SoC consists of a standardized combination of PLEX, CYC, and glucocorticoids.
干预措施: Plasma exchange (PLEX) (Procedure)
Imlifidase and Standard-of-Care (SoC)
Experimental
- Imlifidase is administered IV as one dose of 0.50 mg/kg over 30 minutes.
- SoC consists of a standardized combination of PLEX, CYC, and glucocorticoids.
干预措施: Cyclophosphamide (CYC) (Drug)
Imlifidase and Standard-of-Care (SoC)
Experimental
- Imlifidase is administered IV as one dose of 0.50 mg/kg over 30 minutes.
- SoC consists of a standardized combination of PLEX, CYC, and glucocorticoids.
干预措施: Glucocorticoids (Drug)
Standard-of-Care (SoC)
Active Comparator
SoC consists of a standardized combination of PLEX, CYC, and glucocorticoids.
干预措施: Plasma exchange (PLEX) (Procedure)
Standard-of-Care (SoC)
Active Comparator
SoC consists of a standardized combination of PLEX, CYC, and glucocorticoids.
干预措施: Cyclophosphamide (CYC) (Drug)
Standard-of-Care (SoC)
Active Comparator
SoC consists of a standardized combination of PLEX, CYC, and glucocorticoids.
干预措施: Glucocorticoids (Drug)
结局指标
主要结局
Renal function as evaluated by estimated glomerular filtration rate (eGFR) at 6 months
时间窗: At 6 months after randomisation
次要结局
- Proportion of patients with functioning kidney at 6 months(At 6 months after randomisation)
- Exposure to toxic level of anti-GBM antibodies(From randomisation up to Day 22 and to Day 29 respectively)
- Time to non-toxic level of anti-GBM antibodies(During the study from screening up to 6 months)
- Renal function as evaluated by eGFR at 3 months(At 3 months after randomisation)
- Proportion of patients with functioning kidney at 3 months,(At 3 months after randomisation)
- Proportion of patients experiencing end stage renal disease (ESRD) within 6 months(During the study from randomisation up to 6 months)
- Proportion of patients experiencing death due to anti-GBM disease within 6 months(During the study from randomisation up to 6 months)
- Change in urine creatinine clearance (CrCl) from randomisation to 3 and 6 months(At randomisation and at 3 and 6 months)
- Number of PLEX sessions within 3 months from randomisation(During the study from randomisation up to 3 months)
- U-albumin/creatinine ratio at 3 and 6 months (24h collection)(At screening and at 3 and 6 months)
- U-albumin/creatinine ratio at screening and during study (morning urine void)(During the study from screening up to 6 months)
- Renal function as evaluated by eGFR at screening and during study(During the study from screening up to 6 months)
- Number of days with mechanical ventilation due to anti-GBM disease within 3 months from randomisation(During the study from randomisation to 3 months)
- Number of days at intensive care unit (ICU) and number of days in hospitalisation from randomisation to 3 months(During the study from randomisation to 3 months)
- Number of days on dialysis within 3 and 6 months from randomisation(During the study from randomisation to 3 months and 6 months)
- Proportion of patients being negative during study for anti-GBM antibodies/anti-neutrophilic cytoplasmic autoantibodies (ANCA)/anti-GBM antibodies+ANCA(During the study from screening up to 6 months)
- Change in health related quality of life (HRQoL) from screening to 6 months(At screening and at 6 months)
- Change in health status from screening to 6 months(At screening and at 6 months)
- Pharmacokinetic (PK) data (Cmax) from start of treatment to Day 15(During the study from before administration of imlifidase up to Day 15)
- Imlifidase pharmacodynamic (PD) profile (IgG levels in serum) from start of treatment to Day 15(During the study from before administration of imlifidase up to Day 15)
- Imlifidase pharmacodynamic (PD) profile (composition of different IgG fractions) from start of treatment to Day 15(During the study from before administration of imlifidase up to Day 15)
- Anti-imlifidase antibody levels from start of imlifidase treatment to 6 months(During the study from before administration of imlifidase up to 6 months)
研究者
研究点 (84)
Loading locations...
相似试验
已完成
3 期
Renal Function in Highly Sensitized Patients 1 Year After Desensitization With Imlifidase Prior to DD Kidney TxKidney Transplantation in Highly Sensitized PatientsNCT04935177Hansa Biopharma AB64
已完成
3 期
A Phase 3 Study in Patients With Chronic Kidney Disease and Hyperphosphatemia on Peritoneal DialysisRenal DialysisChronic Kidney DiseaseRenal InsufficiencyNCT01017276Astellas Pharma Inc35
已完成
3 期
PAlbociclib and Circulating Tumor DNA for ESR1 Mutation DetectionMetastatic Breast CancerNCT03079011UNICANCER1,017
已完成
3 期
Efficacy and Safety of Actilyse 2 mg/ 2 ml in Comparison to Saline Solution in Patients With Central Venous Access Device OcclusionCatheter ObstructionVascular Access DevicesNCT01958164Boehringer Ingelheim16
进行中（未招募）
3 期
A Study Comparing BL-B01D1 With Topotecan in Patients With Recurrent Small Cell Lung Cancer(PANKU-Lung03)Small Cell Lung CancerNCT06500026Sichuan Baili Pharmaceutical Co., Ltd.722