An Open-label, Multicenter, Randomized Phase 3 Study Evaluating the Efficacy and Safety of Felzartamab in Participants with Primary Membranous Nephropathy (PMN) [PROMINENT]
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 180
- 试验地点
- 14
- 主要终点
- Percentage of Participants who Achieve Complete Remission (CR) at Week 104
研究概览
简要总结
In this study, researchers will learn more about the use of felzartamab in participants with primary membranous nephropathy, also known as PMN. In people with PMN, autoantibodies build up in the glomeruli of the kidney. Antibodies are proteins that help the body fight off infection. An autoantibody is a type of antibody that mistakenly targets and attacks the body’s own tissues. Glomeruli are the filters of the kidney that remove waste and extra fluid from the body. In PMN, the build-up of autoantibodies in the glomeruli causes damage to the kidneys.
Kidney damage can lead to too much protein and blood leaking into the urine. High levels of protein in the urine, called proteinuria, are common in people with PMN. Symptoms of PMN can include swelling in the legs and body, tiredness, and high blood pressure. If left untreated, PMN can eventually lead to kidney failure.
In this study, researchers will learn more about how a study drug called felzartamab affects people with PMN. Felzartamab is a monoclonal antibody, which means it is an antibody made in a laboratory. Felzartamab can target immune cells that produce autoantibodies, helping to lower their buildup in the kidneys. The main goal of this study is to compare how felzartamab works compared to a drug called tacrolimus. Tacrolimus is another drug given to people with PMN and kidney disease.
The main question that researchers want to answer is:
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How many participants achieve a complete response after 104 weeks of treatment?
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A complete response means that their urine protein levels decrease to a low level and their kidney function remains stable.
Researchers will also learn about:
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How long it takes before the participants’ disease gets worse
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How long the participants’ urine protein levels stay low
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How many participants develop antibodies against felzartamab in the blood?
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How many participants achieve a complete response after 76 weeks of treatment
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How many participants have medical problems during the study
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How felzartamab is processed by the body
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How felzartamab affects participants’ tiredness and overall physical health
The study will be done as follows:
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Participants will be screened to check if they can join the study. This may take up to 42 days.
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Participants will be randomized to receive either felzartamab as intravenous (IV) infusions or tacrolimus, taken orally as tablets.
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If participants have worsening kidney function or worsening proteinuria, or if their PMN relapses, or if they show no signs of improvement in their PMN, they will have a chance to receive rescue treatment.
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If a participant stops treatment early, there will be follow-up visits every 12 weeks until they reach Week 104.
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In total, participants will have up to 23 study visits. Participants who do not need rescue treatment will stay in the study for up to 104 weeks. Participants who need rescue treatment will stay in the study for up to 156 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 80.00 Year(s)（—）
- 性别
- All
入选标准
- •Diagnosed with PMN in need of IST according to the Investigators clinical judgment.
- •The diagnosis of PMN must be documented with the presence of nephrotic syndrome, and hypoalbuminemia, and confirmed with a kidney biopsy either during Screening or within 5 years of signing the informed consent form (ICF) (see kidney biopsy exception below for participants positive for anti-PLA2R antibodies).
- •For these participants, the biopsy report with redacted protected health information must be available to be reviewed by the Sponsor or an independent nephropathologist.
- •If the participant requires a kidney biopsy during Screening, medical monitor approval must be obtained and all other eligibility criteria should be reviewed to ensure that the participant is otherwise eligible prior to performing the kidney biopsy.
- •Kidney biopsy exception for anti-PLA2R antibody positive participants: Participants who are positive for anti-PLA2R antibodies and have not had a kidney biopsy performed within 5 years of signing the ICF, may be eligible for the study without undergoing a kidney biopsy based on medical monitor review confirming normal estimated glomerular filtration rate (eGFR), presence of nephrotic syndrome, hypoalbuminemia, positive anti-PLA2R antibody test (defined as an anti-PLA2R antibody titer greater than 20 RU per mL), and documentation provided by the Investigator that the work-up for secondary causes of membranous nephropathy (MN) was negative with no identifiable secondary causes.
- •Meets one of the following a.
- •Newly diagnosed PMN, defined as having never received IST for PMN in the past.
- •Relapsed PMN defined as documented achievement of CR or partial remission (PR) after treatment with an IST for PMN followed by reappearance of nephrotic range proteinuria (urine protein to creatinine ratio (UPCR) greater than or equal to 3.0 gram per gram from a 24 hour urine collection or proteinuria greater than or equal to 3.5 gram per 24 hour).
- •Participants must be on the maximally approved dose or maximally tolerated dose of angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) for at least 3 months prior to Screening.
- •Participants not on the maximally approved dose of renin angiotensin aldosterone system inhibition may be enrolled provided there is documented intolerance to maximal RAAS inhibition (e.g. angioedema or development of postural hypotension or lightheadedness or hyperkalemia etc)
- •A UPCR of greater than or equal to 3.0 gram per gram (as determined by a 24-hour urine collection) or total proteinuria greater than or equal to 3.5 gram per 24 hour (as determined by a 24-hour urine collection) at Screening after best supportive care for at least 3 months prior to signing the ICF.
排除标准
- •Secondary cause of MN (e.g. malignancies or medications or systemic lupus erythematosus (SLE) or hepatitis B or hepatitis C etc).
- •Severe renal impairment defined as an eGFR less than 30 mL per min per 1.73mx2 at Screening or including the need for dialysis or renal replacement therapy.
- •Note: Other protocol-defined Inclusion/Exclusion criteria may apply.
结局指标
主要结局
Percentage of Participants who Achieve Complete Remission (CR) at Week 104
时间窗: Percentage of Participants who Achieve Complete Remission (CR) at Week 104
次要结局
- Percentage of Participants who Achieve Overall Remission (OR), Defined as CR or Partial Remission (PR) at Week 104(Week 104)
- Percentage of Participants With a Baseline Anti-Phospholipase A2 Receptor (PLA2R) Autoantibody Titer Greater Than 50 Relative Unit per Milliliter (RU/mL) who Achieve an OR at Week 76 and at Week 104(Weeks 76 and 104)
- Percentage of Participants who Achieve CR at Week 76(Week 76)
- Time to Disease Worsening(From Baseline to Week 156)
- Time to a Sustained Reduction in eGFR of greater than or equal to 30 percent From Baseline(From Baseline to week 104)
- Duration of Overall Remission (OR)(From Baseline to week 156)
- Absolute Change in Anti-PLA2R Autoantibody Titer in Participants Positive for Anti-PLA2R at Baseline(From Baseline to week 156)
- Change From Baseline in the Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Scale at Week 104(Week 104)
- Change From Baseline in PROMIS Global Assessment of Physical Health Scale at Week 104(Week 104)
- Number of Participants With Treatment Emergent Adverse Event (TEAE), Serious Adverse Event (SAE) and Adverse Events of Special Interest (AESIs)(From first dose of study drug up to end of follow-up (up to week 156))
- Felzartamab Serum Concentrations Over Time(Predose and at multiple timepoints post dose up to week 156)
- Number of Participants With Anti-Drug Antibodies (ADAs) Against Felzartamab(Predose and at multiple timepoints post dose up to week 156)
研究者
Rashmi Chitgupi
PPD Pharmaceutical Development India Private Limited