A Phase Ib/IIa, Open-Label, Multicenter Clinical Trial to Assess Safety and Efficacy of the Human Anti-CD38 Antibody MOR202 in Anti-PLA2R Antibody Positive Membranous Nephropathy (aMN)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 45
- 主要终点
- Number of Participants With Adverse Events
研究概览
简要总结
This is an open-label, multicentre study to characterize the safety and efficacy of the human anti-CD38 antibody MOR202 in adult subjects with in Anti-PLA2R Antibody Positive Membranous Nephropathy (newly diagnosed/relapsed/refractory)
详细描述
After treatment subjects will be observed for up to 1 year.
Study Sponsor, originally HI-Bio, Inc., is now HI-Bio, A Biogen Company.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
The study is open label as all patients receive the same Investigational Medicinal Product (IMP) and same dose
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •> 18 to < 80 years (at date of signing informed consent form [ICF]).
- •Urine protein to creatinine ratio (UPCR) of ≥ 3.000 g/g OR proteinuria ≥ 3.500 g/24 h from 24-h urine at screening
- •Active anti-PLA2R antibody positive MN in need of immunosuppressive therapy (IST) according to investigator judgement and diagnosed on the basis of a biopsy, archival biopsy acquired within 5 years prior to screening is acceptable.
- •Estimated glomerular filtration rate ≥ 50 ml/min/1.73m² or ≥ 30 and <50 ml/min/1.73m², and interstitial fibrosis and tubular atrophy score of less than 25% on a renal biopsy obtained within the last 6 months prior to start of screening.
- •Not in spontaneous remission despite proper treatment with ACEIs, ARBs (sufficient dose and treatment duration) as per clinical practice and scientific guidelines. If the subject is intolerant to an ACEI or ARB, the reason must be documented and approval obtained prior to enrolment.
- •Systolic blood pressure BP ≤150 mmHg and diastolic BP ≤100 mmHg after 5 minutes of rest
- •Vaccinated against Pneumococcus within the last 5 years prior to date of signing informed consent (subjects may be vaccinated during screening to meet this criterion; interval to first dose of MOR202 must be at least 14 days).
- •Cohort 1 comprises newly diagnosed or relapsed subjects: Serum anti-PLA2R antibodies ≥50.0 RU/mL
- •Cohort 2 comprises therapy refractory subjects: a Subject did not achieve immunological remission after prior IST(s) as documented by the investigator AND b Subject is without promising standard therapeutic options as documented by the investigator (i.e. investigator expects efficacy or safety issues with remaining IST options) AND c Serum anti-PLA2R antibodies ≥ 20.0 RU/mL measured at screening
- •Note: France will only enroll patients in Cohort
排除标准
- •Hemoglobin < 80 g/L.
- •Thrombocytopenia: Platelets < 100.0 x 109/L.
- •Neutropenia: Neutrophils < 1.5 x 109/L.
- •Leukopenia: Leukocytes < 3.0 x 109/L.
- •Hypogammaglobulinemia: Serum immunoglobulins ≤ 4.0 g/L.
- •Subjects may receive supportive therapies to meet the above criteria
- •B-cells < 5 x 106/L.
- •Secondary cause of MN (e.g. Systemic lupus erythematosus, medications, malignancies)
- •Concomitant renal disease other than MN (e.g., diabetic renal disease, lupus nephritis, IgA nephropathy).
研究组 & 干预措施
Cohort 1 (newly diagnosed or relapsed participants)
Participants with newly diagnosed or relapsed membranous nephropathy received MOR202 as an intravenous infusion over 6 treatment cycles of 28-days each. Dosing occurred weekly in Cycle 1 and every 4 weeks in Cycles 2 to 6.
干预措施: MOR202 (Drug)
Cohort 2 (refractory participants)
Participants with membranous nephropathy refractory to immunosuppressive treatment received MOR202 as an intravenous infusion over 6 treatment cycles of 28-days each. Dosing occurred weekly in Cycle 1 and every 4 weeks in Cycles 2 to 6.
干预措施: MOR202 (Drug)
结局指标
主要结局
Number of Participants With Adverse Events
时间窗: Week 1 to Week 24
An adverse event (AE) was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Percentage of Participants With Adverse Events
时间窗: Week 1 to Week 24
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAEs were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
次要结局
- Best Immunological Response Rate (BIRR)(Up to 52 weeks)
- Number of Participants Tested Positive for Anti-felzartamab Antibodies(Baseline; Up to 52 weeks)
- Percentage of Participants Tested Positive for Anti-felzartamab Antibodies(Baseline; Up to 52 weeks)
- Antibody Titers of Participants Tested Positive for Anti-felzartamab Antibodies(Baseline; Up to 52 weeks)
- Felzartamab Serum Concentrations After Multiple Intravenous Administrations(Pre Dose and Post Dose on Cycle 1 Day 1 (C1D1), C1D8, C1D15, C1D22, C2D1, C3D1, C4D1, C5D1, C6D1, End of Treatment (week 24), Follow-up visit (week 38), End of Study (up to 52 weeks))
- Number of Participants With AEs During the Follow-up Period(Week 25 to Week 52)
- Percentage of Participants With AEs During the Follow-up Period(Week 25 to Week 52)