A Phase III, Randomized, Open-label, Active-controlled, Multicenter Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamic and Efficacy of Crovalimab Versus Eculizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Currently Treated With Complement Inhibitors
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 190
- 试验地点
- 115
- 主要终点
- Percentage of Participants With Injection-site Reactions, Infusion-related Reactions, Hypersensitivity and Infections (including Meningococcal Meningitis)
研究概览
简要总结
A study designed to evaluate the safety of crovalimab with eculizumab in participants with PNH currently treated with complement inhibitors. This study will enroll approximately 190 participants.
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
- None
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body weight ≥ 40 kg at screening (pediatric participants with body weight < 40 kg)
- •Treated with eculizumab or ravulizumab for PNH for at least 3 months prior to Day 1
- •Lactate Dehydrogenase Levels ≤ 2x the upper limit of normal (ULN) at screening
- •Willingness and ability to comply with all study visits and procedures
- •Documented diagnosis of PNH, confirmed by high sensitivity flow cytometry
- •Vaccination against Neisseria meningitidis serotypes A, C, W, and Y < 3 years prior to initiation of study treatment; or, if not previously done, vaccination administered no later than one week after the first drug administration
- •Women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for 10.5 months after the final dose of crovalimab or for 3 months after the final dose of eculizumab (or longer if required by the local product label)
排除标准
- •History of allogeneic bone marrow transplantation
- •History of myelodysplastic syndrome with Revised International Prognostic Scoring System (IPSS-R) prognostic risk categories of intermediate, high and very high
- •Pregnant or breastfeeding, or intending to become pregnant during the study, within 10.5 months after the final dose of crovalimab, or 3 months after the final dose of eculizumab (or longer if required by the local product label)
- •Participation in another interventional treatment study with an investigational agent or use of any experimental therapy within 28 days of screening or within 5 half-lives of that investigational product, whichever was greater: participants enrolled in an eculizumab or ravulizumab interventional study are eligible provided they fulfill eligibility (e.g., are willing and able to comply with the study assessments) and stop their participation in current trial before randomisation/enrolment
- •Positive for Active Hepatitis B and C infection (HBV/HCV)
- •Concurrent disease, treatment, procedure, or surgery or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose any additional risk for the participant, or would, in the opinion of the investigator, preclude the participant's safe participation in and completion of the study
- •History of or ongoing cryoglobulinemia at screening
研究组 & 干预措施
Arm C (Crovalimab) (Exploratory)
Participants with a body weight ≥ 5 to <12 kilograms (kg) will receive a loading series of crovalimab doses comprised of an IV dose on Day 1 of Week 1, followed by crovalimab SC dose on Day 2 Week 1. Maintenance doses will begin at Week 3 and will be administered Q2W, thereafter. Participants with a body weight ≥ 12 to < 20 kg and ≥ 20 kg will receive a loading series of crovalimab doses comprised of an IV dose on Day 1 of Week 1, followed by weekly crovalimab SC doses for 4 weeks at Week 1 (Day 2) and then at Weeks 2, 3, and 4. Maintenance doses will begin at Week 5 and will be administered Q2W thereafter, for participants with a body weight ≥ 12 to < 20 kg and Q4W thereafter, for participants with a body weight > 20 kg. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab.
干预措施: Crovalimab (Drug)
Arm A (Crovalimab)
Participants will receive a loading series of crovalimab comprised of an intravenous (IV) dose on Day 1, followed by weekly crovalimab subcutaneous (SC) doses for 4 weeks on Week 1 Day 2, then on Weeks 2, 3, and 4. Maintenance SC dosing will begin at Week 5 and will continue every 4 weeks (Q4W) thereafter for a total of 24 weeks of study treatment. After 24 weeks of crovalimab treatment, participants who derive benefit from the drug may continue to receive crovalimab.
干预措施: Crovalimab (Drug)
Arm B (Eculizumab)
Participants will receive an approved maintenance dose of eculizumab starting on Day 1 and every 2 weeks (Q2W) thereafter for a total of 24 weeks of study treatment. After 24 weeks of study eculizumab treatment, participants will have the option to switch to crovalimab or to discontinue from the study after completion of 10 weeks of safety follow-up.
干预措施: Eculizumab (Drug)
结局指标
主要结局
Percentage of Participants With Injection-site Reactions, Infusion-related Reactions, Hypersensitivity and Infections (including Meningococcal Meningitis)
时间窗: Up to approximately 6 years
Percentage of Participants With Adverse Events (AEs) and by Severity
时间窗: Up to approximately 6 years
Severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5 (CTCAE v5).
Percentage of Participants With Adverse Events (AEs) Leading to Study Drug Discontinuation
时间窗: Up to approximately 6 years
Percentage of Participants With Clinical Manifestations of Drug-target-drug Complex (DTDC) Formation Amongst Those Participants Who Switched to Crovalimab Treatment From Eculizumab Treatment or Ravulizumab Treatment
时间窗: Up to approximately 6 years
次要结局
- Absolute Change From Baseline in Free Hemoglobin and Haptoglobin (mg/dL)(Baseline up to Week 25)
- Serum Concentrations of Crovalimab or Eculizumab Over Time(Up to approximately 6 years)
- Serum Concentrations of Ravulizumab at the Time of Crovalimab Initiation(Baseline)
- Percentage of Participants With Anti-crovalimab Antibodies(Up to approximately 6 years)
- Change in Pharmacodynamic (PD) Biomarker Complement Activity (CH50) Over Time(Up to approximately 6 years)
- Change Over Time in Free C5 Concentration in Crovalimab-treated Participants(Up to approximately 6 years)
- Observed Value in Reticulocyte Count (count/milliliters [mL])(Up to approximately 6 years)
- Observed Value in Free Hemoglobin and Haptoglobin (milligrams per deciliter [mg/dL])(Up to approximately 6 years)
- Absolute Change From Baseline in Reticulocyte Count (count/mL)(Baseline up to Week 25)