A Phase 2, Proof-of-Concept, Randomized, Double-Blinded, Placebo-Controlled Study of ACH-0144471 Treatment for 6 Months in Patients With C3 Glomerulopathy (C3G), With an Open-label Extension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Change From Baseline In Composite Biopsy Score At Week 28
研究概览
简要总结
The primary purpose of this proof-of-concept clinical study was to evaluate the efficacy and safety of the study drug, ACH-0144471 (also known as danicopan and ALXN2040), in participants with C3G who also had significant proteinuria attributable to C3G.
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
- Double (Participant, Investigator)
盲法说明
Investigator and participant blinded; Sponsor open. Participants were randomized 1:1 to receive either danicopan or placebo for a period of 6 months, followed by an open-label extension.
入排标准
- 年龄范围
- 17 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Had biopsy-confirmed primary C3G
- •Had clinical evidence of ongoing disease based on significant proteinuria, attributable to C3G disease in the opinion of the Principal Investigator (PI), and present prior to study entry and confirmed during Screening
- •Was willing to comply with vaccination requirements.
排除标准
- •Had a history or presence of any clinically relevant co-morbidities that would make the participant inappropriate for the study
- •Had ever received danicopan
- •Had more than 50% fibrosis or more than 50% of glomeruli with cellular crescents on the pre-treatment renal biopsy
- •Had an estimated glomerular filtration rate <30 milliliters/minute/1.73 meters squared at the time of screening or at any time over the preceding 4 weeks
- •Was a renal transplant recipient or receiving renal replacement therapy
- •Had a history of a major organ transplant or hematopoietic stem cell/marrow transplant
- •Had evidence of monoclonal gammopathy of unclear significance, infections, malignancy, autoimmune diseases, or other conditions to which C3G is secondary
- •Had other renal diseases that would interfere with interpretation of the study
- •Had been diagnosed with or showed evidence of hepatobiliary cholestasis
- •Females who were pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration
- •Had a 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
- •Had evidence of human immunodeficiency virus, hepatitis B infection, or active hepatitis C infection at Screening
- •Had laboratory abnormalities at screening that, in the opinion of the PI, would make the participant inappropriate for the study
研究组 & 干预措施
Danicopan (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period)
Danicopan was administered at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then dosage was to be increased to 200 mg TID for the remainder of the 6-month treatment period.
All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID.
干预措施: Danicopan (Drug)
Placebo (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period)
Placebo was administered TID during the 6-month treatment period.
All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID.
干预措施: Danicopan (Drug)
Placebo (Double-blind Treatment Period), Followed by Danicopan (Open-label Extension Period)
Placebo was administered TID during the 6-month treatment period.
All participants who completed the double-blind treatment period were enrolled in the open-label extension period and were to receive danicopan 200 mg TID.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline In Composite Biopsy Score At Week 28
时间窗: Baseline, Week 28
The composite biopsy score was based on a score incorporating changes in the activity index, glomerular C3c staining, and glomerular macrophage infiltration at the end of 6 months of treatment. The composite renal biopsy index scoring system ranged from 0 to 21, with higher scores indicating worse outcomes.
Participants With Reduction In Proteinuria At Week 28
时间窗: Week 28
Proteinuria reduction was defined as ≥ 30% decrease from baseline based on 24-hour urine protein (mg/day).
次要结局
- Slope Of Estimated Glomerular Filtration Rate (eGFR) After Open-label Danicopan Treatment(12 months)
- Change From Baseline In eGFR At Week 28(Baseline, Week 28)
- Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To 6 Months(6 months)
- Participants With Significant Improvement In eGFR Relative To Baseline At Week 28(Baseline, Week 28)
- Change From Baseline In Proteinuria At Week 28(Baseline, Week 28)
- Percent Change From Baseline In Proteinuria At Week 28(Baseline, Week 28)
- Participants With Significant Improvement In eGFR Relative To Baseline At Week 52(Baseline, Week 52)