NCT03124368已完成2 期
A Phase 2a Proof-of-Mechanism, Open-Label Study to Determine the Effect of ACH-0144471 on C3 Levels in Participants With Low C3 Levels Due to Either C3 Glomerulopathy (C3G) or Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15
研究概览
简要总结
The primary objective of this study was to determine whether ACH-0144471 (also known as danicopan and ALXN2040) increases blood C3 complement protein (C3) levels in participants with low C3 levels due to either C3G or IC-MPGN.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have had clinical diagnosis of C3G (C3 glomerulonephritis or dense deposit disease, the 2 types of C3G) or idiopathic IC-MPGN by renal biopsy for at least 3 months prior to dosing, with the pathologic diagnosis verified by a review of the renal biopsy by the study central pathologist
- •C3 must have been <50% of the lower limit of normal
- •C4 complement protein (C4) must have been >90% of the lower limit of normal
- •Must have been willing to comply with study-specific vaccination requirements for Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis strains A, C, W, and Y
- •Negative pregnancy test for females prior to dosing and throughout the study
排除标准
- •History of a major organ transplant (for example, heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant. Individuals receiving renal replacement therapy were also excluded
- •Evidence of monoclonal gammopathy of unclear significance, infections, malignancy, autoimmune diseases, or other conditions to which C3G or IC-MPGN may have been secondary
- •Estimated glomerular filtration rate (using Modification of Diet in Renal Disease equation) <45 milliliters/minute/1.73 square meters at the time of Screening or at any time over the preceding 4 weeks
- •Receipt of eculizumab at any dose or interval within the past 75 days prior to dosing
- •Use of tacrolimus or cyclosporine within 2 weeks of the first dose of danicopan
- •History of febrile illness, a body temperature >38°Celsius, or other evidence of a clinically significant active infection, within 14 days prior to study drug administration
- •History of meningococcal infection, or a first-degree relative or household contact with a history of meningococcal infection
- •Females who were pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration or participants with a female partner who was pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration
研究组 & 干预措施
Group 1: Danicopan 100 mg TID (Sentinel)
Experimental
All participants received 100 milligrams (mg) of danicopan three times per day (TID) during the Treatment Period.
干预措施: Danicopan (Drug)
Group 2: Danicopan up to 200 mg TID
Experimental
All participants received not more than 200 mg of danicopan TID depending on the available safety, pharmacokinetic, and pharmacodynamic data from Group 1 (Sentinel) during the Treatment Period.
干预措施: Danicopan (Drug)
结局指标
主要结局
Change From Baseline In Serum C3 Complement Protein (C3) Levels On Day 15
时间窗: Baseline, Day 15
Serum C3 levels were measured by conventional Roche immunoturbidimetric assay method. Change from Baseline = Serum C3 levels on Day 15 - Baseline Serum C3 levels
Change From Baseline In Plasma Intact C3 Level On Day 15
时间窗: Baseline, Day 15
Plasma Intact C3 level were measured by a novel multiplex assay method. Change from Baseline = Plasma Intact C3 levels on Day 15 - Baseline Plasma Intact C3 levels
次要结局
- Change From Baseline In Total Complement Classical Pathway (CP) Activity On Day 14(Baseline, Day 14)
- Change From Baseline In Total Complement Alternative Pathway (AP) Functional Activity (AP Wieslab) On Day 15(Baseline, Day 15)
- Time To Achieving Peak Serum C3 Levels(From The First Day Of Dosing through Day 14)
- Number Of Participants With Serious Adverse Events (SAEs), Grade 3 And Grade 4 Treatment-emergent Adverse Events (TEAEs), And Adverse Events (AEs) Leading To Discontinuation(Up to Day 49)
- Pharmacokinetics (PK): Area Under The Plasma Concentration-time Curve From Time Of Administration To 8 Hours Postdose (AUC0-8)(Days 1 and 7)
- PK: Maximum Plasma Concentration (Cmax)(Days 1 and 7)
- PK: Time To Maximum Concentration (Tmax)(Days 1 and 7)
- Change From Baseline In Bb Fragment Of Complement Factor B (Bb) At Day 15(Baseline, Day 15)
- Change From Baseline In Soluble Terminal Complement Complex (sC5b-9) At Day 15(Baseline, Day 15)
研究者
研究点 (1)
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