A Double Blind, Randomized, Placebo-Controlled, Multicenter Phase IIa, Clinical Trial to Assess Efficacy and Safety of the Human Anti-CD38 Antibody Felzartamab in IgA Nephropathy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 106
- 主要终点
- Efficacy: Relative change in Proteinuria value
研究概览
简要总结
Randomized, placebo-controlled, multi-center, double-blind, proof of concept phase IIa trial and dose evaluation trial of felzartamab in IgAN
详细描述
Study Sponsor, originally HI-Bio, Inc., is now HI-Bio, A Biogen Company.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients ≥ 18 to ≤ 80 years (at date of signing the informed consent form [ICF]), but at least of legal age in the given country
- •Biopsy confirmed diagnosis of IgAN within the past 8 years prior to signature of the ICF
- •Proteinuria at screening visit ≥ 1.0 g/d.
- •Treatment with an angiotensin-converting enzyme inhibitor (ACEi) and/or angiotensin receptor blocker (ARB) at maximum doses or maximally tolerated doses for ≥ 3 months prior to date of informed consent and adequate blood pressure (BP) control.
- •A female of childbearing potential (FCBP), is only eligible to participate if she is not pregnant, not breast feeding, and agrees to follow the contraceptive guidance during the treatment period and for at least 3 months after the last dose of IMP
排除标准
- •Hemoglobin < 90 g/L
- •Thrombocytopenia: Platelets < 100.0 x 10^9/L.
- •Neutropenia: Neutrophils < 1.5 x 10^9/L.
- •Leukopenia: Leukocytes < 3.0 x 10^9/L
- •Diabetes mellitus type 1
- •Aspartate aminotransferase or alanine aminotransferase >1.5 x ULN, alkaline phosphatase >3.0 x ULN
研究组 & 干预措施
Part 2: Japan Cohort
Japanese participants were administered felzartamab as an IV infusion based on their body weight on Days 1,8,15, 22, 29, 57, 85, 113 and 141.
干预措施: Felzartamab (Drug)
Part 1: Felzartamab Dosing Arm M3
Participants were administered felzartamab as an IV infusion based on their body weight on Days 1,8,15, 22, 29, 57, 85, 113 and 141.
干预措施: Felzartamab (Drug)
Part 1: Placebo
Participants were administered felzartamab matching placebo as an intravenous (IV) infusion on Days 1, 8, 15, 22, 29, 57, 85, 113 and 141.
干预措施: Placebo (Other)
Part 1: Felzartamab Dosing Arm M1
Participants were administered felzartamab as an IV infusion based on their body weight on Days 1 and 15, and felzartamab matching placebo on Days 8, 22, 29, 57, 85, 113 and 141.
干预措施: Felzartamab (Drug)
Part 1: Felzartamab Dosing Arm M1
Participants were administered felzartamab as an IV infusion based on their body weight on Days 1 and 15, and felzartamab matching placebo on Days 8, 22, 29, 57, 85, 113 and 141.
干预措施: Placebo (Other)
Part 1: Felzartamab Dosing Arm M2
Participants were administered felzartamab as an IV infusion based on their body weight on Days 1, 8,15, 29, and 57, and felzartamab matching placebo on Days 22, 85, 113 and 141.
干预措施: Felzartamab (Drug)
Part 1: Felzartamab Dosing Arm M2
Participants were administered felzartamab as an IV infusion based on their body weight on Days 1, 8,15, 29, and 57, and felzartamab matching placebo on Days 22, 85, 113 and 141.
干预措施: Placebo (Other)
结局指标
主要结局
Efficacy: Relative change in Proteinuria value
时间窗: 9 months compared to baseline
Part 1: Relative Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) in 24-hour Urine at Month 9
时间窗: Baseline, Month 9
Proteinuria is high levels of protein in the urine and is measured by UPCR. Relative change in UPCR was estimated based on mixed effects model for repeated measure (MMRM) model. Least squares (LS) mean and standard error (SE) were reported. The reference proteinuria value before start of treatment is defined as the mean of the values determined at screening and prior to baseline (visit 2) predose (UPCR from 24h urine). Negative change from baseline indicates less proteinuria.
次要结局
- Pharmacokinetic: serum concentrations of Felzartamab over time(Ongoing through treatment completion, up to 2 years)
- Safety: determined by the frequency, incidence and severity of TEAEs(Ongoing through study completion, up to 2 years)
- Efficacy: Relative change in proteinuria value(Ongoing through treatment completion, an average every 3 months per treatment period, up to 2 years)
- Efficacy: complete response in patients with IgAN(Ongoing through treatment completion, an average every 3 months per treatment period, up to 2 years)
- Integrative Analysis of Several Endpoints: Percent Change From Baseline in Immunoglobulin A (IgA) Concentration by Predose Serum Concentration (Ctrough) Group(Up to 9 months)
- Integrative Analysis of Several Endpoints: Maximum Serum Concentrations (Cmax) as Per the Infusion-Related Reactions (IRRs) After the First Dose(Up to 1 week)
- Part 1: Time to Response(Up to 2 years)
- Part 1: Relative Change From Baseline in UPCR in 24-hour Urine at Months 3, 6, 12, 18 and 24(Baseline, Months 3,6,12,18 and 24)
- Part 1: Number of Participants With Complete Response (CR) at Months 3, 6, 9, 12, 18 and 24(Months 3,6,9,12,18 and 24)
- Part 1: Percentage of Participants With Response at Months 3, 6, 9, 12, 18 and 24(Months 3,6,9,12,18 and 24)
- Part 1: Albumin-Creatinine Ratio (ACR) at Months 6, 9, 12, 18 and 24(Months 6, 9,12,18 and 24)
- Part 1: Duration of Response(Up to 2 years)
- Change From Baseline in eGFR Over Time(Baseline, Months 3,6,9,12,15,18, and 24)
- Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE)(From the first dose until 28 days after last dose of study drug (up to 191 days))
- Serum Concentrations of Felzartamab Over Time(Predose and 30 minutes post-dose on Days 1, 15, 29; predose on Days 8, 57, 85, 113, 141; Post Treatment Days 169 and 267)
- Percentage of Participants With Anti- Felzartamab Antibodies(From the first dose up to the end of the study (up to 2 years))