NCT03157037已完成2 期
Open-Label Phase II Study in Anti-GBM Disease (Goodpasture's Disease) With Adverse Renal Prognosis to Evaluate the Efficacy and Safety of IdeS - GOOD-IDES
Mårten Segelmark19 个研究点 分布在 5 个国家目标入组 15 人开始时间: 2017年6月16日最近更新:
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 19
- 主要终点
- Number of Patients With Independent Renal Function at 6 Months
研究概览
简要总结
This study will evaluate the safety and tolerability of IdeS in patients with severe anti-glomerular basement membrane (anti-GBM) disease receiving standard of care consisting of pulse-methylprednisolone, oral prednisolone and intravenous cyclophosphamide combined with plasma exchange (PLEX).
详细描述
This is an Open-Label Phase 2 Study to Evaluate the Efficacy and Safety of IdeS in anti-GBM disease (Goodpasture's disease, i.e. GP) with Adverse Renal Prognosis. The primary efficacy objective is to evaluate the efficacy of an IdeS based regimen to salvage independent renal function measured as no need for dialysis at 6 months after IdeS treatment. The primary safety objective of this study is to evaluate the safety and tolerability of IdeS in patients with severe anti-GBM disease on background of standard care consisting of pulse-methylprednisolone, oral prednisolone and intravenous cyclophosphamide (CYC) combined with plasma exchange (PLEX). The patients will be followed during 6 months according to the study visit plan.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 detected by ELISA above a level that is considered toxic by the investigator using local laboratory. Patients double-positive for anti-GBM and anti-neutrophil cytoplasmic antibodies (ANCAs) may be entered in the trial, but only if their level of anti-GBM antibodies fulfil the criteria listed above.
- •Estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m^2 (by modification of diet in renal disease (MDRD) equation) or if the patient is non-responsive to standard treatment, and has lost >15 ml/min/1.73 m^2 after start of treatment
- •Haematuria on dipstick and/or urinary sediment
- •Male or female patients aged at least 18 years; Female patients of childbearing potential may participate if highly effective contraception is used during the study, according to Clinical Trials Facilitation and Coordination Group (CTFG) guidance [18], see also section 4.9 (pregnancy test should be performed before inclusion).
- •Willing and able to give written Informed Consent and to comply with the requirements of the study protocol; and
- •Judged to be otherwise healthy by the Investigator, based on medical history, physical examination, and clinical laboratory assessments. Patients with clinical laboratory values that are outside of normal limits (other than those specified in the
排除标准
- •) and/or with other abnormal clinical findings that are judged by the Investigator not to be of clinical significance, may be entered into the study.
- •Exclusion Criteria:
- •Anuria for more than 2 days (less than 200 ml during last 48 hours);
- •Dialysis dependency for more than 5 days (maximum 3 sessions before signing informed consent);
- •Ongoing moderate to severe pulmonary haemorrhage (or having ceased within the last two weeks), defined as requiring assisted ventilation, oxygen or blood transfusions.
- •Symptomatic congestive heart failure (NYHA class 2-4) and requiring prescription medication or clinically evident peripheral edema of cardiac origin;
- •Myocardial infarction, unstable angina or stroke within 3 months prior to screening;
- •Ongoing bacterial infection requiring antibiotic therapy or viral infection with Hepatitis B, C or HIV (up to 3 months old negative test results are accepted); or active tuberculosis as indicated by chest x-ray.
- •Patients should not have received investigational drugs within 30 days prior to screening or within 4 half-lives (whichever is longer); and
- •History or presence of any medical condition or disease which, in the opinion of the Investigator, may place the subject at unacceptable risk for study participation.
结局指标
主要结局
Number of Patients With Independent Renal Function at 6 Months
时间窗: 6 months after dosing
Number of patients without need for dialysis at 6 months. A patient with independent renal function is defined as a patient without need for dialysis.
次要结局
- Renal Function at 3 and 6 Months(3 and 6 months after imlifidase dosing)
- Number of Patients With Haematuria (Blood in Urine)(At 6 months after dosing)
- Pharmacokinetics of Imlifidase (AUC)(Pre-dose, 45min, 2h, 6h, 24h, Day3, Day 7, Day 10, and Day15)
- Renal Histology(Before administration of imlifidase (0-33 days) and after administration of imlifidase (3-6 days))
- Number of Patients With Anti-GBM Antibodies Above a Toxic Level Stratified by Number of Study Visits(Predose up to 6 months after dosing)
- Number of Patients With Renal Function Over Time Stratified by Ranges of eGFR(Pre-imlifidase, 1, 3 and 6 months after imlifidase dosing)
- Pharmacokinetics of Imlifidase (t1/2)(Pre-dose, 45min, 2h, 6h, 24h, Day3, Day 7, Day 10, and Day15)
- Pharmacokinetics of Imlifidase (CL)(Pre-dose, 45min, 2h, 6h, 24h, Day3, Day 7, Day 10, and Day15)
- Number of Patients With Independent Renal Function at 3 Months(3 months after dosing)
- Number of PLEXs Needed Over Time(Pre-screening and up to Day 93 after imlifidase dosing)
- Change in Proteinuria During the Study(Pre-imlifidase, 3 and 6 months after imlifidase dosing)
- Pharmacokinetics of Imlifidase (Cmax)(Pre-dose, 45min, 2h, 6h, 24h, Day3, Day 7, Day 10, and Day15)
- Anti-imlifidase Antibodies (ADA)(Up to 6 months after dosing)
- Pharmacokinetics of Imlifidase (Vz)(Pre-dose, 45min, 2h, 6h, 24h, Day3, Day 7, Day 10, and Day15)
- Pharmacodynamics (IgG Degradation Measured as Remaining Concentration of Intact and Single Cleaved IgG)(Pre-dose up to 6 months after imlifidase administration)
研究者
Mårten Segelmark
MD, PhD and Professor Department of Drug Research, Department of Medical and Health Sciences
Linkoeping University
研究点 (19)
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