A Phase 2 Open-label Study of ACH-0144471 in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Who Have an Inadequate Response to Eculizumab Monotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Change From Baseline In Hemoglobin At Week 24
研究概览
简要总结
To determine the effectiveness of ACH-0144471 (also known as danicopan and ALXN2040) in improving anemia when given with eculizumab for 24 weeks in participants with PNH. Danicopan dose may be increased within each participant, to a maximum of 200 milligrams (mg) three times daily (TID) based on safety and efficacy at protocol-specified time points.
详细描述
The purpose of this study is to determine the effectiveness of danicopan in improving anemia, as measured by increased blood hemoglobin, when given with eculizumab (a drug commonly used for treatment of PNH) for 24 weeks in participants with PNH.
The 24-week treatment period was followed by a long-term extension phase. In the extension phase, participants received the same danicopan dose plus eculizumab as they were receiving at the end of 24-week treatment phase.
Results are reported for the 24-week treatment period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with PNH
- •Have received at least one red blood cell transfusion within last 12 weeks
- •Anemia with adequate reticulocytosis
- •Must be on a stable regimen of eculizumab
- •Platelet count ≥ 40,000/microliter without the need for platelet transfusions
- •Documentation of vaccination for Neisseria meningitidis, Haemophilus influenza, and Streptococcus pneumoniae or willingness to receive vaccinations based on local guidelines
- •Willingness to receive antibiotic prophylaxis
- •Female participants must use highly effective birth control to prevent pregnancy during the clinical trial and for 30 days after their last dose of study drug
- •Male participants must use a highly effective birth control with a female partner to prevent pregnancy during the clinical trial and for 90 days after the last dose of study drug
排除标准
- •Current evidence of bone marrow failure or aplastic anemia requiring treatment
- •History of a major organ transplant or hematopoietic stem cell/marrow transplant
- •Received another investigational agent within 30 days or 5 half-lives of the investigational agent prior to study entry, whichever is greater
- •Documented C5 complement protein mutations
- •Known or suspected complement deficiency
- •Contraindication to any of the required vaccinations
- •Active bacterial infection or clinically significant active viral infection, a body temperature >38°C, or other evidence of infection
- •History of meningococcal infection, or a first-degree relative or household contact with a history of meningococcal infection
- •History of hypersensitivity reactions to commonly used antibacterial agents
- •Note: Additional inclusion/exclusion criteria may apply, per protocol.
研究组 & 干预措施
Group 1: 100 mg Danicopan TID + Eculizumab
Starting dose of 100 mg danicopan TID in combination with eculizumab.
干预措施: Danicopan (Drug)
Group 1: 100 mg Danicopan TID + Eculizumab
Starting dose of 100 mg danicopan TID in combination with eculizumab.
干预措施: Eculizumab (Drug)
Group 2: Initial dose 100 or 150 mg Danicopan TID + Eculizumab
Starting dose of 100 or 150 mg danicopan TID in combination with eculizumab.
干预措施: Danicopan (Drug)
Group 2: Initial dose 100 or 150 mg Danicopan TID + Eculizumab
Starting dose of 100 or 150 mg danicopan TID in combination with eculizumab.
干预措施: Eculizumab (Drug)
Group 3: Initial dose of 100, 150, or 200 mg Danicopan TID + Eculizumab
Starting dose of 100, 150, or 200 mg danicopan TID in combination with eculizumab.
干预措施: Danicopan (Drug)
Group 3: Initial dose of 100, 150, or 200 mg Danicopan TID + Eculizumab
Starting dose of 100, 150, or 200 mg danicopan TID in combination with eculizumab.
干预措施: Eculizumab (Drug)
Group 4: Optimal Dose of Danicopan TID + Eculizumab
Optimal dose (starting dose of either 100, 150, or 200 mg, as determined from Groups 1-3) of danicopan TID in combination with eculizumab.
干预措施: Danicopan (Drug)
Group 4: Optimal Dose of Danicopan TID + Eculizumab
Optimal dose (starting dose of either 100, 150, or 200 mg, as determined from Groups 1-3) of danicopan TID in combination with eculizumab.
干预措施: Eculizumab (Drug)
结局指标
主要结局
Change From Baseline In Hemoglobin At Week 24
时间窗: Baseline, Week 24
次要结局
- Number Of Units Of Red Blood Cells (RBCs) Transfused During 24 Weeks Of Treatment(Within 24 weeks prior to first dose and during 24-week treatment period)
- Change From Baseline In Lactate Dehydrogenase At Week 24(Baseline, Week 24)
- Number Of Participants Without RBC Transfusions During 24 Weeks Of Treatment(Within 24 weeks prior to first dose and during 24-week treatment period)
- Number Of Participants With Serious Adverse Events (SAEs), Grade 3 And Grade 4 Adverse Events (AEs), And Events Leading To Discontinuation Of Study Drug(Day 1 (after dosing) through end of study (maximum exposure: 1631 days))