NCT02598583已完成1 期
An Open-Label, Intrapatient, Dose-Escalation Study to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of ALXN1210 Administered Intravenously to Patients With Paroxysmal Nocturnal Hemoglobinuria
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 8
- 主要终点
- Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169
研究概览
简要总结
This study evaluated the safety, tolerability, efficacy, pharmacokinetics, pharmacodynamics, and immunogenicity of multiple intravenous (IV) doses of ALXN1210 administered to participants with PNH who have not previously been treated with complement inhibitor.
详细描述
The data presented is up to the Primary Completion date of the study and is for the 24-week Primary Evaluation period. The study also includes an Extension Period of up to 5 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Male or female ≥18 years of age
- •PNH diagnosis confirmed by documented high-sensitivity flow cytometry
- •Documented meningococcal vaccination not more than 3 years prior to dosing
- •Female participants of childbearing potential used highly effective contraception starting at screening and continuing until at least 24-weeks after the last dose of ALXN1210
- •Willing and able to give written informed consent and comply with the study visit schedule
排除标准
- •Treatment with a complement inhibitor at any time
- •Females who were pregnant, breastfeeding or who had a positive pregnancy test at screening or Day 1
- •Participation in an interventional clinical study within 30 days before initiation of dosing on Day 1, or use of any experimental therapy within 30 days prior to dosing on Day 1, or within 5 half-lives of the product, whichever is greater
- •History of allergy to excipients of ALXN1210 or known allergy to Chinese hamster ovary cell proteins
- •Inability to comply with study requirements
- •History of any clinically significant cardiac, hepatic, immunologic, pulmonary, or rheumatoid disease that, in the Investigator's judgment, would preclude participation
- •Other unspecified reasons that, in the opinion of the Investigator or Sponsor, made the participant unsuitable for enrollment
研究组 & 干预措施
Cohort 2
Experimental
Participants were administered ALXN1210 1800 mg.
In the Extension period participants continued at the same dose and frequency as the Primary Evaluation Period.
干预措施: ALXN1210 (Biological)
Cohort 1
Experimental
Participants were administered ALXN1210 900 mg.
In the Extension period participants continued at the same dose and frequency as the Primary Evaluation Period.
干预措施: ALXN1210 (Biological)
结局指标
主要结局
Percent Change In Lactate Dehydrogenase (LDH) Levels From Baseline To Day 169
时间窗: Baseline, Day 169
Baseline was defined as the average of all available assessments prior to first ALXN1210 infusion.
次要结局
- Cmax/D At Day 1 And Day 141(Day 1 and Day 141)
- AUCt/ Dose-normalized (D) At Day 1(Day 1)
- Percent Change In Haptoglobin Levels From Baseline To Day 169 And Day 1821(Baseline, Day 169, Day 1821)
- Maximum Observed Serum Concentration (Cmax) At Day 1 And Day 141(Day 1 and Day 141)
- Concentration At The End Of The Dosage Interval (Ctrough) At Day 1 And At Day 141(Day 1 and Day 141)
- Percent Change In Free Hemoglobin Levels From Baseline To Day 169 And Day 1821(Baseline, Day 169, Day 1821)
- Time To Maximum Observed Serum Concentration (Tmax) At Day 1 And Day 141(Day 1 and Day 141)
- Percent Change In Chicken Red Blood Cell (cRBC) Hemolysis From Baseline To Day 1709(Baseline, Day 1709)
- Percent Change In Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clones From Baseline To Day 169 And Day 1933(Baseline, Day 169, Day 1933)
- Percent Change In Free Complement Component 5 (C5) Concentration From Baseline To Day 1709(Baseline, Day 1709)
- Percent Change In Total C5 Concentration From Baseline To Day 1709(Baseline, Day 1709)
- Percent Change In Reticulocyte/Erythrocyte Count From Baseline To Day 169 And Day 1821(Baseline, Day 169, Day 1821)
- Percent Change In D-dimer Levels From Baseline To Day 169 And Day 1821(Baseline, Day 169, Day 1821)
- Change In Clinical Manifestations Of PNH From Baseline To Day 169 And Day 1821(Baseline, Day 169, Day 1821)
- Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The Last Quantifiable Concentration (AUCt) At Day 1(Day 1)
- Area Under The Serum Concentration-versus-time-curve From Time 0 (Dosing) To The End Of The Dosing Interval (AUCtau) At Day 141(Day 141)
- AUCtau/D At Day 141(Day 141)
- Participants Experiencing Antidrug Antibodies (ADAs)(Day 1821)
研究者
研究点 (8)
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