A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Felzartamab in Adults With IgA Nephropathy (PREVAIL)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Biogen
- 入组人数
- 454
- 试验地点
- 369
- 主要终点
- Percent Change From Baseline in Proteinuria as Measured by the Urine Protein: Creatinine Ratio (UPCR)
研究概览
简要总结
In this study, researchers will learn more about the use of felzartamab in participants with immunoglobulin A nephropathy (IgAN). IgAN is a kidney disease caused by the buildup of an antibody called IgA in the kidneys over time. In people with IgAN, abnormal IgA and other antibodies form clusters that build up in the small filters of the kidneys, which leads to inflammation and damage. Felzartamab is designed to target certain immune cells that produce these abnormal antibodies. This study will focus on participants who have protein in their urine (proteinuria) as a result of damaged kidneys.
The main goal of the study is to learn about the effect felzartamab has on proteinuria. The main question that researchers want to answer is:
• How much does the amount of protein in the urine change from the start of the study to Week 36?
Researchers will learn about the effect felzartamab has on the kidneys' ability to filter blood. They will also learn more about the safety of felzartamab and how it is processed by the body.
The study will be done as follows:
- Participants will be screened to check if they can join the study.
- Participants will be randomized to receive either felzartamab or a placebo. A placebo looks like the study drug but contains no real medicine.
- Neither the researchers nor the participants will know what the participants will receive.
- Participants will receive felzartamab or placebo as intravenous (IV) infusions. The treatment period will last 24 weeks.
- Afterwards, participants will enter a follow-up period which will last 80 weeks.
- In total, participants will have 17 study visits. Participants will stay in the study for about 2 years.
详细描述
The primary objective of the study is to evaluate the efficacy of felzartamab compared to placebo on proteinuria in participants with Immunoglobulin A nephropathy (IgAN). The main secondary objective of the study is to evaluate the efficacy of felzartamab compared to placebo on kidney functions in participants with IgAN. The additional secondary objectives are to evaluate the efficacy of felzartamab compared to placebo on additional clinical endpoints and to assess the pharmacokinetics (PK) and immunogenicity of felzartamab.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Biopsy-confirmed diagnosis of IgAN within the past 10 years prior to signature of the informed consent form (ICF). For participants with diabetes mellitus type 2, an IgAN diagnostic biopsy within the past 24 months prior to signing the ICF.
- •An eGFR ≥ 30 mL/min/1.73 m^2 at Screening as calculated using the 2021 chronic kidney disease epidemiology (CKD-EPI) creatinine formula. An eGFR of ≥ 20 and < 30 mL/min/1.73 m^2 is acceptable for the cohorts 3 and
- •Proteinuria of ≥ 1.0 gram per day (g/day) or UPCR ≥0.8 gram per gram (g/g) as assessed by an adequate 24-hour urine collection.
- •Clinically stable on a maximally tolerated dose or maximally approved dose of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) for at least 12 weeks prior to Screening. Participants may also be using sodium-glucose cotransporter-2 inhibitors (SGLT2is); endothelin receptor antagonists (ERAs) or dual endothelin angiotensin receptor antagonist (DEARAs) approved for the treatment of IgAN; and/or mineralocorticoid receptor antagonists (MRAs) as long as the dose is stable for at least 12 weeks prior to Screening. Participants should remain on stable doses of these background medications for the duration of the study. Once the ICF is signed and thereafter, the doses cannot be changed during the study nor the drugs discontinued except if deemed related to an AE. Participants using a DEARA (e.g., sparsentan) will not be permitted to use simultaneous ACEI or ARB medication.
排除标准
- •Any history of secondary forms of IgAN, indicated by the presence of any other systemic disease potentially leading to IgA deposits as determined by the Investigator.
- •History of rapidly progressive variant of IgAN, defined as eGFR loss by > 50% per 3 months and not explained by changes in renin-angiotensin system (RAS) blockade or other factors.
- •IgAN-(MCD) variant.
- •Concomitant other progressive glomerulonephritis or non-immunologic glomerular disease such as diabetic nephropathy.
- •Type 2 diabetes mellitus with Hemoglobin A1c (HbA1c) > 8% at Screening, or evidence of diabetic nephropathy on biopsy, history of diabetic microvascular or macrovascular disease (eg, diabetic retinopathy, peripheral neuropathy).
- •Any diagnosed or suspected immunosuppressed or immunodeficient state such as asplenia, human immunodeficiency virus (HIV), primary immunodeficiencies, organ or bone marrow transplantation, with the exception of corneal transplants.
- •Previously treated with immunosuppressive or other immunomodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), cyclosporine, tacrolimus, sirolimus, everolimus, or systemic glucocorticoid exposure (> 7.5 milligrams per day [mg/d] prednisone-equivalent for indications other than IgAN or any dose if given for the treatment of IgAN) within 4 months prior to Screening. Use of hydroxychloroquine in Mainland China is allowed if the candidate has been on this for at least 6 months prior to Screening with a stable dose for at least 12 weeks prior to Screening. If a potential participant requires systemic glucocorticoids at any dose for IgAN during Screening, this will result in a screen fail. If a potential participant requires systemic glucocorticoids > 7.5 mg/day prednisone-equivalent for indications other than IgAN during Screening, this will result in a screen fail.
- •Participants currently treated with oral budesonide. Participants who have stopped this therapy ≥ 4 months prior to Screening may be eligible.
- •Active clinically significant infections, known history of recurrent clinically significant infection, or Screening laboratory evidence consistent with an active infection, or non-prophylactic treatment with IV anti-infectives (antibacterials, antiviral or antifungals). Participants with a history of opportunistic infections are excluded.
- •Hypogammaglobulinemia: serum Immunoglobin G (IgG) < 6.0 gram per litre (g/L), at Screening.
- •Note: Other protocol-defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Cohort 2
Participants will receive several IV doses of placebo.
干预措施: Placebo (Drug)
Cohort 4
Participants with an eGFR ≥ 20 and <30 mL/min/1.73m^2 will receive several IV doses of placebo.
干预措施: Placebo (Drug)
Cohort 1
Participants will receive several intravenous (IV) doses of felzartamab.
干预措施: Felzartamab (Drug)
Cohort 3
Participants with an estimated glomerular filtration rate (eGFR) ≥ 20 and <30 milliliter per minute per 1.73 square meter (mL/min/1.73m^2) will receive several IV doses of felzartamab.
干预措施: Felzartamab (Drug)
结局指标
主要结局
Percent Change From Baseline in Proteinuria as Measured by the Urine Protein: Creatinine Ratio (UPCR)
时间窗: Baseline up to Week 36
次要结局
- Percentage of Participants Requiring Rescue Therapy(Baseline up to Week 104)
- Percentage of Participants who Progressed to Kidney Malfunction(Baseline up to Week 104)
- Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) Values Calculated Using the Chronic Kidney Disease Epidemiology (CKD-EPI) Creatinine Equation(Baseline up to Week 104)
- Percentage of Participants Achieving Complete Response (CR)(Baseline up to Week 104)
- Change From Baseline in eGFR Values Calculated Using the CKD-EPI Creatinine Equation(Baseline up to Week 52)
- Felzartamab Serum Concentrations Over Time(Predose and at multiple timepoints postdose up to Week 36)
- Number of Participants with Anti-Drug Antibodies (ADAs) Against Felzartamab(Baseline up to Week 104)
- Percentage of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE)(Baseline up to Week 104)
- Number of Participants With Clinically Significant Change From Baseline in Vital Signs Abnormalities(Baseline up to Week 104)
- Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities(Baseline up to Week 104)
- Number of Participants With Clinically Significant Change From Baseline in Electrocardiogram (ECG) Abnormalities(Baseline up to Week 104)
- Number of Participants With Clinically Significant Change From Baseline in Physical Examinations Abnormalities(Baseline up to Week 104)