NCT05067127已完成3 期
A Phase 3, Randomized, Placebo-Controlled, Double-Blinded, Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With C3 Glomerulopathy or Immune-Complex Membranoproliferative Glomerulonephritis
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 124
- 试验地点
- 123
- 主要终点
- Randomized Controlled Period: Change From Baseline in Log-Transformed Urine Protein-to-Creatinine Ratio (uPCR) at Week 26
研究概览
简要总结
This is a Phase 3 study to assess the efficacy and safety of twice-weekly subcutaneous (SC) doses of pegcetacoplan compared to placebo in patients with C3 glomerulopathy (C3G) or immune-complex membranoproliferative glomerulonephritis (IC-MPGN) on the basis of a reduction in proteinuria.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged at least 18 years; where approved, adolescents (aged 12-17 years) weighing at least 30 kg may also be enrolled.
- •A diagnosis of primary C3G or IC-MPGN (with or without previous renal transplant).
- •Evidence of active renal disease, based on one or more of the following:
- •In adults or adolescents with a baseline renal biopsy (either one collected during screening or a historic biopsy collected within 28 weeks prior to randomization), at least 2+ C3c staining on the baseline renal biopsy.
- •In adolescents not providing a baseline renal biopsy, at least one of the following:
- •Plasma sC5b-9 level above the upper limit of normal during screening
- •Serum C3 below the LLN during screening
- •Presence of an active urine sediment during screening, as evidenced by hematuria with at least 5 red blood cells (RBCs) per high-power field (HPF) and/or red blood cell casts on local or central microscopic analysis of urine.
- •Presence of C3 nephritic factor within 6 months of screening, based on central laboratory results or medical history.
- •No more than 50% global glomerulosclerosis or interstitial fibrosis on the baseline biopsy for adult participants or adolescent participants providing a baseline biopsy.
- •At least 1 g/day of proteinuria on a screening 24-hour urine collection and a uPCR of at least 1000 mg/g in at least 2 first-morning spot urine samples collected during screening.
- •eGFR ≥30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease-Epidemiology Collaboration creatinine equation for adults or the Bedside Schwartz equation for adolescents.
- •Stable regimen for C3G/IC-MPGN treatment, as described below:
- •Angiotensin-converting enzyme inhibitor/, angiotensin receptor blocker, and/or sodium-glucose cotransporter-2 inhibitor therapy that is stable and optimized, in the opinion of the investigator, for at least 12 weeks prior to randomization
- •Stable doses of other medications that can affect proteinuria (eg, steroids, mycophenolate mofetil, and/or other allowed immunosuppressants that the participant is receiving for treatment of C3G or IC-MPGN) for at least 12 weeks prior to the baseline renal biopsy and randomization.
- •If a participant is on prednisone (or other systemic corticosteroid) for C3G or IC-MPGN treatment, the dosage is stable and no higher than 20 mg/day (or equivalent dosage of a corticosteroid other than prednisone) for at least 12 weeks prior to randomization.
- •Have received vaccinations against S pneumoniae, N meningitidis (types A, C, W, Y, and B), and H influenzae (type B) within 5 years prior to randomization or agree to receive vaccinations during screening.
排除标准
- •Previous exposure to pegcetacoplan.
- •C3G/IC-MPGN secondary to another condition (eg, infection, malignancy, monoclonal gammopathy, a systemic autoimmune disease such as systemic lupus erythematosus, chronic antibody-mediated rejection, or a medication), in the opinion of the investigator.
- •Current or prior diagnosis of human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV) infection or positive serology during screening that is indicative of infection with any of these viruses.
- •Body weight greater than 100 kg at screening.
- •Hypersensitivity to pegcetacoplan or to any of the excipients.
- •History of meningococcal disease.
- •Malignancy, except for the following:
- •Cured basal or squamous cell skin cancer
- •Curatively treated in situ disease
- •Malignancy-free and off treatment for ≥5 years
- •Severe infection (eg, requiring IV antibiotic therapy) within 14 days prior to the first dose of pegcetacoplan.
- •An absolute neutrophil count <1000 cells/mm3 at screening.
- •Use of rituximab, belimumab, or any approved or investigational anticomplement therapy other than pegcetacoplan within 5 half-lives of that product prior to the screening period.
- •Female participants who are pregnant or who are currently breastfeeding and are unwilling to discontinue for the duration of the study and for at least 90 days after the final dose of study drug.
- •Presence or suspicion of severe infection during the screening period (including but not limited to recurrent or chronic infections) that, in the opinion of the investigator, may place the participant at unacceptable risk by study participation.
- •Known or suspected hereditary fructose intolerance.
研究组 & 干预措施
Group 1: Pegcetacoplan administration
Experimental
Subcutaneous infusion of 20mL (1080 mg), twice weekly (for adults or adolescents >50kg), and the three other weight-based doses either of 10mL (540mg), 12mL (648mg), or 15mL (810mg)
干预措施: Pegcetacoplan (Drug)
Group 2: Placebo administration
Placebo Comparator
Subcutaneous infusion of either 10mL, 12mL, 15mL, or 20mL, twice weekly
干预措施: Placebo (Other)
结局指标
主要结局
Randomized Controlled Period: Change From Baseline in Log-Transformed Urine Protein-to-Creatinine Ratio (uPCR) at Week 26
时间窗: Baseline (Day -70 to Day 1) to Week 26
Baseline uPCR value was calculated as the average of the uPCR measurements from at least 6 of the 9 first-morning spot urine (FMU) samples collected between the start of screening and Day 1, inclusive. The uPCR values used to calculate baseline included those from the samples collected on Day -2, Day -1, and before dosing on Day 1. In situations where less than 6 samples or more than 9 samples were collected, the average of all collected samples was used for baseline derivation. The difference between treatment groups using a composite contrast of equal-weighted average over Weeks 24, 25, and 26 was estimated.
次要结局
- Randomized Controlled Period: Percentage of Subjects Who Achieved the Composite Renal Endpoint at Week 26(Week 26)
- Randomized Controlled Period: Change From Baseline in the C3 Glomerulopathy (C3G) Histologic Index Activity Score at Week 26(Baseline (Day 1) and Week 26)
- Randomized Controlled Period: Percentage of Subjects With a Reduction of At Least 50% From Baseline in Urine Protein-to-Creatinine Ratio at Week 26(Baseline (Day -70 to Day 1) and Week 26)
- Randomized Controlled Period: Percentage of Subjects Who Showed Decrease in C3c Staining on Renal Biopsy From Baseline at Week 26(Baseline (Day 1) and Week 26)
- Randomized Controlled Period: Change From Baseline in the Kidney Disease Quality of Life (KDQOL) Score at Week 26(Baseline (Day 1) and Week 26)
- Randomized Controlled Period: Change From Baseline in Estimated Glomerular Filtration Rate at Week 26(Baseline (Day 1) and Week 26)
- Randomized Controlled Period: Percentage of Subjects Who Achieved Proteinuria <1 Gram (g)/Day at Week 24(Week 24)
- Randomized Controlled Period: Percentage of Subjects With Normalization of Serum Albumin Levels at Week 26(Week 26)
- Randomized Controlled Period: Percentage of Subjects With Serum C3 Levels Above the Lower Limit of Normal at Week 26(Week 26)
- Randomized Controlled Period: Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 26(Baseline (Day 1) and Week 26)
研究者
研究点 (123)
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相关资讯
Pegcetacoplan Shows Strong Efficacy in C3G and IC-MPGN Patients: VALIANT Trial Results• Pegcetacoplan demonstrated a statistically significant 68% reduction in proteinuria compared to placebo in patients with C3G and IC-MPGN.
• The VALIANT trial showed pegcetacoplan stabilized eGFR, a key measure of kidney function, with a significant difference compared to placebo.
• A substantial proportion of patients treated with pegcetacoplan achieved complete clearance of C3c deposits, a key marker of disease activity.
• Pegcetacoplan exhibited a favorable safety profile, with similar rates of adverse events compared to the placebo group in the VALIANT trial.last yearPegcetacoplan Shows Promise in Treating Rare Kidney Diseases C3G and IC-MPGN• Phase 3 VALIANT study reveals pegcetacoplan significantly reduces proteinuria by 68% in patients with C3G and IC-MPGN compared to placebo.
• Pegcetacoplan stabilizes eGFR, a key measure of kidney function, and substantially reduces C3c deposits, a marker of disease activity.
• The treatment demonstrates a favorable safety profile, with adverse event rates similar between the pegcetacoplan and placebo groups.
• Apellis plans to submit regulatory applications to the FDA and EMA for pegcetacoplan as a treatment for C3G and IC-MPGN in early 2025.last year