A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Evaluate the Efficacy and Safety of VIS649 in Participants With Immunoglobulin A (IgA) Nephropathy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 155
- 试验地点
- 93
- 主要终点
- Number of Participants With Adverse Events Graded by Severity
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of VIS649 in participants with immunoglobulin A (IgA) Nephropathy (IgAN)
详细描述
This is a Phase 2, double-blind, randomized, placebo-controlled study in patients aged 18 years and above with biopsy confirmed diagnosis of IgAN. The study is designed to test the safety and effectiveness of multiple doses of VIS649. The main objectives are to evaluate the safety and tolerability of VIS649 and to evaluate the dose response of different doses of VIS649 by measuring proteinuria.
The study is comprised of three main periods, Screening, Treatment (12 months) and Follow-Up (4 months). Approximately 144 patients will be enrolled. The findings from this study will form the basis for subsequent clinical development of VIS649.
VIS649 is a humanized immunoglobulin G (IgG2) monoclonal antibody that binds to and blocks the biological actions of the cytokine A PRoliferation Inducing Ligand (APRIL), a key factor in the production of aberrantly glycosylated IgA1 (a-g- IgA1), which is critical to the pathogenesis of IgAN.
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)
盲法说明
Patient, Investigator, Care Provider, 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
- •Participants are eligible to be included in the study only if all of the following criteria apply:
- •Participant is a male or female ≥ 18 years of age at the time of signing the informed consent.
- •Participant must have biopsy-confirmed IgAN.
- •Participant has medical records showing they have been on stable and maximally tolerated doses of either ACEI or ARB, as per local SOC and applicable guidelines, for at least 3 months preceding screening. Participants should optimally be on at least 50% of the maximum recommended dose of these agents; however, if a participant is on their maximally tolerated dose (and this is < 50% of the maximum recommended dose) and has been on this dose for at least 3 months, they may be enrolled. Participants who are unable to tolerate ACEI/ARB therapy may be eligible for participation in the study if their overall management of IgAN, including BP control, is as per local SOC and applicable guidelines.
- •Participants must have screening uPCR ≥ 0.75 g/g measured from a 24-hour urine or 24-hour urine protein ≥ 1.0 g/d, as measured from 24-hour urine collection. The proteinuria should be assessed when the participant is considered to be in a steady state with no recent heavy exercise, fever, or other potential issues that could impact the result.
- •Participants must have eGFR ≥ 45 mL/min/1.73 m² using the CKD-EPI formula.
- •Participant's serum Ig values must meet specified criteria
- •Female participants of childbearing potential must have a negative serum pregnancy test prior to the first dose.
- •Participant is willing to adhere to contraceptive requirements.
- •Participant or a legally authorized representative is able and is willing to give voluntary written informed consent
排除标准
- •Participants are excluded from the study if they meet any of the following criteria:
- •Participant has secondary forms of IgAN as defined by the treating physician.
- •Participant has co-existing CKD, other than IgAN.
- •Participant has evidence of additional pathological findings in the kidney biopsy (eg, diabetic kidney disease, membranous nephropathy, or lupus nephritis). However, hypertensive vascular changes are acceptable.
- •Participant has kidney biopsy MEST or MEST-C score as defined in the protocol.
- •Participant has nephrotic syndrome.
- •Participant has received a solid organ transplant, including kidney.
- •Participant has received bone marrow or hematologic stem cell transplantation.
- •Participant is currently receiving systemic immunosuppression (excluding topical, ophthalmic, per rectum, or inhaled corticosteroids).
- •Participant has received treatment with systemic corticosteroid therapy within 16 weeks of initial screening.
- •Participant has received treatment with a systemic immunosuppressive agents within 16 weeks of initial screening.
- •Participant has any chronic infectious disease.
- •Participant has acute infectious disease at the time of screening.
- •Participant has Type 1 diabetes.
- •Participant has uncontrolled Type 2 diabetes, as evidenced by a screening hemoglobin A1c value > 8%.
- •Participant has uncontrolled BP (> 140 mm Hg systolic or > 90 mm Hg diastolic)
- •Participant has a history of chronic autoimmune neurodegenerative disorder such as multiple sclerosis.
- •Participant has a known allergy or intolerance to any component of the study intervention.
- •Participant is breastfeeding.
- •Participant has poorly compensated or controlled ischemic heart disease or cardiomyopathy, as judged by the Investigator.
- •Participant has chronic obstructive pulmonary disease (COPD) or asthma that has required systemic steroid therapy during the prior year.
- •Participant has known cirrhosis or liver dysfunction, defined as presence of coagulopathy, platelet count < 100,000/μL or alanine aminotransferase > 3× upper limit of normal.
- •Participant has active malignancy or is receiving chemotherapy for malignancy, except for nonmelanoma skin cancers and cervical carcinoma in situ. Participants with prior malignancy who have been documented to be cancer-free for ≥ 5 years may be enrolled.
- •Participant is planning or scheduled to undergo a tonsillectomy. Prior tonsillectomy is acceptable (if greater than 6 months prior to screening).
- •Participant enrolled in another investigational drug or device study within 3 months prior to initial screening.
- •Participant with a pre-existing illness other than those listed above that, in the opinion of the Investigator, would place the participant at increased risk through participation in this study.
- •Participant is unable to comply with study protocol procedures and/or study visit schedules.
- •Participant with known or suspected alcohol or drug abuse that would compromise their safety or study participation of the participant, in the opinion of the Investigator.
研究组 & 干预措施
Placebo
Placebo, normal saline (0.9% NaCl) will be administered IV
干预措施: Dose-Placebo (Drug)
Low Dose - VIS649
Low dose of VIS649 administered IV
干预措施: Low Dose-VIS649 (Drug)
Medium Dose - VIS649
Medium dose of VIS649 administered IV
干预措施: Medium Dose-VIS649 (Drug)
High Dose - VIS649
High dose of VIS649 administered IV
干预措施: High Dose-VIS649 (Drug)
结局指标
主要结局
Number of Participants With Adverse Events Graded by Severity
时间窗: Baseline to End of Study (16 months)
The number of participants who experienced adverse events, graded by maximum severity, are presented.
Changes From Baseline in Clinical Laboratory Tests
时间窗: Baseline to End of Study (16 months)
The number of participants who experience a shift from normal at baseline to Grade 3/4 (moderate/sever) at a postbaseline time point are presented.
Clinically Meaningful Changes From Baseline in Vital Signs
时间窗: Baseline to End of Study (16 months)
The number of participants who experienced clinically meaningful changes from baseline in vital signs (body mass index, diastolic blood pressure, height, heart rate, mean arterial pressure, respiratory rate, systolic blood pressure, temperature, and weight) are presented.
Clinically Significant Physical Examinations
时间窗: Baseline to End of Study (16 months)
Clinically significant physical examination findings are presented.
Change From Baseline in uPCR: Month 12
时间窗: 12 months
Natural Log 24-Hour uPCR (Schedule A Urine Collection) Change from Baseline at Month 12: mixed model with repeated measurements
次要结局
- Change From Baseline in uPCR: Months 9 and 16(Baseline to 9 months and 16 months (16 months total))
- Change in 24-hour Urine Protein Excretion: Months 12 and 16(16 months)
- Participants Achieving a Greater Than or Equal to 30% Decline From Baseline in uPCR at Months 9, 12, and 16(Baseline to 9,12, and 16 months (16 months total))
- Participants in Each Group Achieving Clinical Remission(Baseline to End of Study (16 months))
- Change From Baseline in eGFR at Months 9, 12, and 16(Baseline to 12 and 16 months)
- Percent Change From Baseline in Total Serum IgA, IgG, and IgM Concentrations at Months 12 and 16(Baseline to 12 and 16 months)
- Mean Serum PK Parameters at Month 0 and Month 11: Cmax(Months 0 and 11)
- Median Serum PK Parameters at Month 0 and Month 11: Tmax(Month 0 and Month 11)
- Mean Serum PK Parameters at Month 0: AUC0-inf and AUC0-30(Month 0)
- Mean Serum PK Parameters at Month 0 and Month 11: t1/2z(Month 0 and Month 11)
- Median Serum PK Parameters at Month 0: CL(Month 0)
- Mean Serum PK Parameters at Month 0: Vz(Month 0)
- Mean Serum PK Parameters at Month 11: AUCτ(Month 11)
- Mean Serum PK Parameters at Month 11: Vss(Month 11)
- Mean Serum PK Parameters at Month 11: CLss(Month 11)
- Mean Serum PK Parameters at Month 11: Rac[AUC0-30](Month 11)