Phase 4, Single-Arm Study of Ravulizumab in Adult Participants With Paroxysmal Nocturnal Hemoglobinuria Currently Treated With High-Dose Eculizumab
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- Percentage of Participants Who Experienced Free C5-associated BTH
研究概览
简要总结
The primary purpose of this study is to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of ravulizumab in participants who are prescribed and are receiving a higher than approved dose of eculizumab to treat paroxysmal nocturnal hemoglobinuria (PNH).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented diagnosis of PNH, confirmed by high-sensitivity flow cytometry evaluation of red blood cells and white blood cells, with granulocyte or monocyte clone size of ≥ 5%.
- •Received 1200 mg eculizumab every 12 to 16 days (every 2 weeks) for at least 3 months prior to Screening.
- •LDH ≤ 2 x upper limit of normal (ULN) according to central laboratory, at Screening.
- •To reduce the risk of meningococcal infection (Neisseria meningitidis), all participants must be vaccinated against meningococcal infections within 3 years prior to initiating study drug.
- •Body weight ≥ 40 kilograms.
排除标准
- •History of major adverse vascular events within 6 months of Day
- •History of bone marrow transplantation.
- •Lymphoma, leukemia, myelodysplastic syndrome, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
- •Concomitant use of anticoagulants is prohibited if not on a stable regimen for at least 2 weeks prior to Day
- •Concomitant use of any of the following medications and not on a stable regimen (as judged by the Investigator) for the time period indicated prior to Screening:
- •Erythropoietin or immunosuppressants for at least 8 weeks
- •Systemic corticosteroids for at least 4 weeks
- •Vitamin K antagonists (for example, warfarin) with a stable international normalized ratio level for at least 4 weeks
- •Iron supplements or folic acid for 4 weeks
- •Live vaccine(s) within 1 month prior to Screening or plans to receive such vaccines during the study.
- •More than 1 LDH value > 2 × ULN within the 6 months prior to Day
- •Platelet count < 30,000/cubic millimeter (30 × 10^9/Liter [L]) at Screening.
- •Absolute neutrophil count < 500/microliter (0.5 × 10^9/L) at Screening.
研究组 & 干预措施
Ravulizumab
Participants will receive eculizumab during the 3-month Screening Period. Participants will then switch over to and receive weight-based doses of ravulizumab for the duration of the study Treatment Period (351 days).
干预措施: Eculizumab (Biological)
Ravulizumab
Participants will receive eculizumab during the 3-month Screening Period. Participants will then switch over to and receive weight-based doses of ravulizumab for the duration of the study Treatment Period (351 days).
干预措施: Ravulizumab (Biological)
结局指标
主要结局
Percentage of Participants Who Experienced Free C5-associated BTH
时间窗: Baseline through Day 351
Free C5-associated BTH was defined as BTH concurrent with free C5 concentrations ≥0.5 micrograms (μg)/milliliter (mL). BTH was defined as at least one new or worsening symptom or sign of intravascular hemolysis (fatigue, hemoglobinuria, abdominal pain, shortness of breath \[dyspnea\], anemia \[hemoglobin \<10 grams {g}/deciliter {dL}\], major adverse vascular event \[MAVE\], including thrombosis, dysphagia, or erectile dysfunction) in the presence of elevated lactate dehydrogenase (LDH) ≥2 \* upper limit of normal (ULN).
次要结局
- Percentage of Participants Who Experienced BTH(Baseline through Day 351)
- Percentage of Participants With Stabilized Hemoglobin(Baseline through Day 351)
- Percent Change From Baseline in LDH at Day 351(Baseline, Day 351)
- Percentage of Participants Who Received a Red Blood Cell (RBC) Transfusion(Baseline through Day 351)