2024-513744-28-00已完成2 期
Rescue Therapy with the Human Anti-CD38 Antibody MOR202 (felzartamab) in Patients with Membranous Nephropathy who Failed Anti-CD20 Target Therapy (MONET study)
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 2
- 主要终点
- Reduction in 24-hour urinary protein excretion at 12 months after the first MOR202 administration compared to baseline.
研究概览
简要总结
To evaluate the efficacy of MOR202 in reducing and/or abrogating urinary protein excretion in MN patients with nephrotic-range proteinuria who are resistant to or dependent from anti-CD20 antibodies.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Age ≥18 years
- •Biopsy-proven membranous nephropathy with or without detectable circulating anti-PLA2R or anti-THSD7A antibodies
- •Background treatment with RAS blocking agents (ACE inhibitor and/or ARBs), at maximum tolerated doses and adequately controlled blood pressure (BP <140/90 mmHg in at least three consecutive readings at screening).
- •One condition between: • Anti-CD20 Resistance: residual proteinuria ≥3.5 g/day (mean of three consecutive 24-hour urine collections), with less than 50% reduction compared to pre-treatment values at least 12 months after anti-CD20 antibody therapy. • Anti-CD20 Dependence: frequently relapsing NS (nephrotic-range proteinuria for >50% of time in the last five years or since disease onset, whichever is shorter) despite repeated treatments with anti-CD20 antibodies.
- •Estimated GFR >30 ml/min/1.73m2 (CKD-EPI equation) and less than 50% of sclerotic glomeruli in patients receiving renal biopsy.
- •A minimum 12-month wash-out from last anti-CD20 therapy with rituximab and/or other monoclonal antibodies
- •No immunosuppressive therapy with steroid, cyclophosphamide, cyclosporine, mycophenolate mofetil or any other immunosuppressant over the last 6 months; in case of therapies administered for less than 2 weeks, no washout time will be required prior to inclusion.
- •Completed anti SARS Cov 2 Vaccination
- •Written informed consent
排除标准
- •Clinically relevant neutropenia (neutrophils < 1.5 x 109/L), anemia (Hb levels <9.0 g/dL), thrombocytopenia (platelet count < 150.000/mm3), increased liver transaminase or bilirubin levels (total bilirubin, aspartate aminotransferase or alanine aminotransferase >1.5 x ULN, alkaline phosphatase >3.0 x ULN).
- •Participation in other clinical trials within 4 weeks of signing the consent form
- •Expected need of anti SARS Cov 2 vaccination during the study period
- •Pregnancy or breast-feeding
- •Childbearing potential in males and females non using an highly effective method of contraception according to 2020 CTFG Recommendations related to contraception and pregnancy testing in clinical trials
- •Legal incapacity or limited legal capacity
- •Significant uncontrolled cardiovascular disease (including arterial or venous thrombotic or embolic events over the last three months) or cardiac insufficiency (New York Heart Association [NYHA] class IV) as judged by the investigator.
- •Clinically relevant findings on a 12-lead electrocardiogram (ECG) as determined by the investigator at screening
- •History of significant cerebrovascular disease (stroke or transitory ischemic attack over the last three months) or sensory or motor neuropathy of toxicity ≥ grade
- •Any clinical condition that in the investigator judgment could affect the possibility to complete the study or could have a major confounding effect on study findings and data interpretation
- •Known intolerance to the study drug or its excipients
- •Any viral, bacterial or fungal infection without complete symptoms resolution from at least two weeks
- •Serologic or virologic markers positive for HIV, hepatitis C (patients with positive antihepatitis C virus [anti-HCV] antibody but negative HCV RNA polymerase chain reaction [PCR] can enroll) or active or latent hepatitis B (patients with positive hepatitis B surface antigen [HBsAg] are excluded). Patients with isolated positive hepatitis B core antibody [anti-HBc], hepatitis B virus (HBV) DNA test by PCR must be non-detectable to enroll.
- •History of malignancy within the prior 5 years
结局指标
主要结局
Reduction in 24-hour urinary protein excretion at 12 months after the first MOR202 administration compared to baseline.
Reduction in 24-hour urinary protein excretion at 12 months after the first MOR202 administration compared to baseline.
Composite endpoint of complete remission (24-hour urinary protein excretion <0.3 g or urinary protein to creatinine ratio < 300 mg/g, with serum albumin > 3.5 g/dL) or partial remission (24-hour urinary protein excretion <3.5 g or urinary protein to creatinine ratio < 3500 mg/g, with at least 50% reduction compared to baseline) of nephrotic syndrome at 12 months from the first infusion.
Composite endpoint of complete remission (24-hour urinary protein excretion <0.3 g or urinary protein to creatinine ratio < 300 mg/g, with serum albumin > 3.5 g/dL) or partial remission (24-hour urinary protein excretion <3.5 g or urinary protein to creatinine ratio < 3500 mg/g, with at least 50% reduction compared to baseline) of nephrotic syndrome at 12 months from the first infusion.
次要结局
- Reduction in 24-hour urinary protein excretion at 6, 9, 12, 18 and 24 months
- Complete remission at 6, 9, 12, 18 and 24 months
- Composite endpoint of complete or partial remission at 6, 9, 12, 18 and 24 months.
- Depletion of circulating anti-PLA2R (defined as titers < 2 RU/mL by commercially available kits) or anti-THSD7A (defined as negative IIF test) at 6, 9, 12, 18 and 24 months from treatment in patients with PLA2R-related or THSD7A-related MN.
- Time to NS relapse (defined as 24-hour proteinuria increase to >3.5 g in subjects with previous complete or partial remission)
- Time to re-emergence of anti-PLA2R or anti-THSD7A in patients with initial depletion
- Changes at 6, 9, 12, 18 and 24 months compared to baseline values in: body weight, serum albumin, anti-PLA2R or anti-THSD7A antibody levels, triglycerides, cholesterol (total, LDL, HDL)
- Changes at 6, 12, 18 and 24 months compared to baseline values in GFR, RPF, as well as albumin, IgG and sodium fractional clearance and calculated FF, RVR and glomerular resistances
- Changes in the frequency of circulating T- and NK-cell subpopulations and in B-cell subsets including plasmablasts and plasma cells
- Changes in quality of Life (QoL) assessed by the SF-36 questionnaire
- PK profile of MOR202 determined by serum concentrations over time
- MOR202 immunogenicity, i.e. frequency of anti-MOR202 antibodies (ADA) detection after therapy
- Serious and non-serious adverse events
- Frequency, incidence, seriousness, relatedness, and severity of treatment-emergent adverse events (TEAEs), including severe hypersensitivity reactions to MOR202 (acute grade III or IV adverse reactions requiring advanced care, or late reactions including delayed serum sickness syndrome) that, independent of response to treatment, may preclude further exposure to the drug.
研究者
monet@marionegri.it
Scientific
Istituto Di Ricerche Farmacologiche Mario Negri
研究点 (2)
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