A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Felzartamab in Adults with IgA Nephropathy
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 454
- 试验地点
- 18
- 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). 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.
• Afterwards, participants will enter a follow-up period.
• In total, participants will have 17 study visits. Participants will stay in the study for about 2 years.
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
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研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
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, biopsy confirmation of IgAN diagnosis must be done within the past 24 months prior to signing the ICF.There is no upper limit of age
- •An eGFR greater than or equal to 30 milliliters per minute per 1.73 square meters at Screening as calculated using the 2021 chronic kidney disease epidemiology (CKD-EPI) creatinine formula.
- •An eGFR of greater than or equal to 20 and less than 30 milliliters per minute per 1.73 square meters is acceptable for the cohorts 3 and
- •Proteinuria of greater than or equal to 1.0 gram per day or UPCR greater than or equal to 0.8 gram per gram 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, or intolerant of ACEI or ARB.
- •If intolerant, this must be discussed with the Medical Monitor prior to randomization.
- •Participants may also be using sodium-glucose cotransporter-2 inhibitors (SGLT2is), endothelin receptor antagonists (ERAs) 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 sparsentan will not be permitted to use simultaneous ACEI or ARB medication.
排除标准
- •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 greater than 50% per 3 months and not explained by changes in renin-angiotensin system (RAS) blockade or other factors.
- •Nephrotic syndrome presumed to be due to minimal change disease (MCD) variant.
- •Concomitant other progressive glomerulonephritis or non-immunologic glomerular disease such as diabetic nephropathy.
- •5 Type 2 diabetes mellitus with Hemoglobin A1c (HbA1c) greater than 8% at Screening, or evidence of diabetic nephropathy on biopsy, history of diabetic microvascular or macrovascular disease (eg, diabetic retinopathy, peripheral neuropathy).
- •6 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.
- •7 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 corticosteroids exposure (greater than 7.5 milligrams per deciliter [mg/d] prednisone/prednisolone equivalent) within 4 months (or 12 months for rituximab) prior to Screening.
- •8 Participants currently treated with oral budesonide.
- •Participants who have stopped this therapy greater than or equals to 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 IV anti-infectives (antibacterials, antiviral or antifungals).
- •Participants with a history of opportunistic infections are excluded.
- •10 Hypogammaglobulinemia: Serum Immunoglobin G (IgG) less than 6.0 gram per litre, at Screening.
- •Note: Other protocol-defined Inclusion/Exclusion criteria may apply.
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
- 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)(CR is defined as a UPCR value (based on 24-hour urine collection) of greater than 0.5 gram per gram (g/g), a reduction in UPCR of greater than and equals to 50%, and a stable eGFR (decrease from baseline in eGFR of less than and equals to 25%). Baseline up to Week 104)
- Percentage of Participants who Progressed to Kidney Malfunction.(The percentage of participants progressing to kidney malfunction will be reported based on one of the following, 1. greather than or equals to 40% Reduction in eGFR Sustained for greaterthan or equals to 30 Days, 2. eGFR less than 15 mL/min/1.73m^2 for greater than or equals to 30 Days, 3. Undergoing Dialysis for greater than or equals to 30 Days, 4. Undergoing Kidney Transplantation, 5. Died From Kidney Failure)
- Percentage of Participants Requiring Rescue Therapy(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)
研究者
Rashmi Chitgupi
PPD Pharmaceutical Development India Private Limited, part of Thermo Fisher Scientific