A Phase 2, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Surovatamig in Adults With Antibody-mediated Kidney Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 43
- 试验地点
- 24
- 主要终点
- Number of participants with adverse events.
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability, pharmacokinetic, and efficacy of surovatamig administered by subcutaneous injection in adult participants with primary membranous nephropathy.
详细描述
This is a Phase II open-label study to assess the safety, tolerability, Pharmacokinetics, and efficacy of surovatamig in adult participants with pMN, who are positive for anti-PLA2R antibodies and have heavy and persistent proteinuria with a high risk of progressing to end stage kidney disease.
The study will be conducted across approximately 30 to 40 study sites in approximately 10 countries. The study consists of 2 parts (Part A Multiple ascending with sentinel dosing and Part B Multiple ascending doses), with each consisting of 3 periods (ie, screening period, treatment period, and follow-up period; up to 26 months in total).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be 18 (or the legal age of consent in the jurisdiction in which the study is taking place) to 75 years of age inclusive, at the time of signing the informed consent.
- •Diagnosis of anti-PLA2R antibody-positive pMN.
- •All participants must have received SoC therapy with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for ≥ 4 weeks, with exceptions in case of intolerance, contraindications, or low blood pressure, before the screening period.
- •Positive for anti-PLA2R.
- •Up to date with required vaccinations as per institutional guidelines (eg, influenza, pneumococcal, and severe acute respiratory syndrome coronavirus 2) prior to study entry.
- •Male and/or female assigned at birth, inclusive of all gender identities. Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Capable of giving signed informed consent
排除标准
- •Receipt of B cell-depleting therapy including CD19- or CD20-directed monoclonal antibodies < 9 months before screening.
- •Immunomodulatory therapy <3 months before screening.
- •Secondary causes of membranous nephropathy
- •Diabetes mellitus with haemoglobin A1C > 8.5% tested at screening visit.
- •Malignancies
- •History of HLH/MAS. 7 Significant CNS co-morbidity
- •8. History of chronic significant respiratory disease.
- •Significant opportunistic infection in the medical history deemed relevant by the Investigator.
- •10. Abnormal vital sign after 10 minutes sitting at rest.
- •Administration of corticosteroids such as prednisolone at doses exceeding 20 mg or an equivalent agent < 2 months before screening.
研究组 & 干预措施
Surovatamig Arm
Participants will receive Surovatamig
干预措施: Surovatamig (Drug)
结局指标
主要结局
Number of participants with adverse events.
时间窗: Through study completion, an average of 2 years
To assess the safety and tolerability of surovatamig on adverse events, including Adverse events, Serious adverse events, Adverse event of special interests, and Adverse events leading to discontinuation of surovatamig.
Change from baseline in UPCR (from 24-hour urine collection or the intended 24-hour urine collection)
时间窗: At 6 months
To assess the effect of surovatamig on proteinuria
次要结局
- Percentage of participants achieving partial remission of pMN(At 24 months)
- Percentage of participants achieving complete or partial remission of pMN(At 24 months)
- Percentage of participants achieving complete remission of pMN(At 24 months)
- Change from baseline in UPCR (from 24-hour urine collection or the intended 24-hour urine collection)(At 24 months)
- Change from baseline in anti-PLA2R antibody titer(At 24 months)
- Change from baseline in B-cell count in peripheral blood(At 24 months)
- Time to relapse after complete or partial remission(At 24 months)
- Time to a ≥ 3 months sustained reduction of eGFR(From Baseline to 24 months)
- Change from baseline in patient-reported experience of symptoms associated with pMN(Through study completion, an average of 2 years)
- Serum PK parameters of surovatamig, AUC Area under the plasma concentration versus time curve(Through study completion, an average of 2 years)
- Treatment-emergent ADAs(Through study completion, an average of 2 years)
- Serum PK parameters of surovatamig, as Cmax (Peak Plasma Concentration)(Through study completion, an average of 2 years)