A Multicenter, Single-arm, Open-label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily Iptacopan in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Marginal Proportion (Expressed as Percentage) of Participants With Sustained Increase in Hemoglobin Levels From Baseline of ≥ 2 g/dL in the Absence of Red Blood Cell Transfusions
研究概览
简要总结
The purpose of this Phase 3 study was to determine whether iptacopan is efficacious and safe for the treatment of Paroxysmal nocturnal hemoglobinuria (PNH) patients who were naïve to complement inhibitor therapy.
详细描述
This study was a multicenter, single-arm, open-label trial which was comprised of 8 weeks screening period, 24-week core treatment period and 24-week extension treatment period.
Eligible PNH patients with hemolysis (LDH > 1.5 ULN) and anemia (hemoglobin <10 g/dL), who were naive to complement inhibitor therapy, including anti-C5 antibody treatment, received iptacopan monotherapy at a dose 200 mg orally b.i.d.
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
- •Male and female participants ≥ 18 years of age with a diagnosis of PNH confirmed by high-sensitivity flow cytometry with RBCs and WBCs clone size ≥ 10%
- •Mean hemoglobin level <10 g/dL
- •LDH > 1.5 x Upper Limit of Normal (ULN)
- •Vaccination against Neisseria meningitidis infection is required prior to the start of study treatment
- •If not received previously, vaccination against Streptococcus pneumoniae and Haemophilus influenzae infections should be given
排除标准
- •Prior treatment with a complement inhibitor, including anti-C5 antibody
- •Known or suspected hereditary complement deficiency
- •History of hematopoietic stem cell transplantation
- •Patients with laboratory evidence of bone marrow failure (reticulocytes <100x109/L; platelets <30x109/L; neutrophils <0.5x109/L).
- •Active systemic bacterial, viral (incl. COVID-19)or fungal infection within 14 days prior to study drug administration.
- •History of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus.
- •Major concurrent comorbidities including but not limited to severe kidney disease (e.g., dialysis), advanced cardiac disease (e.g., NYHA class IV heart failure), severe pulmonary disease (e.g., severe pulmonary hypertension (WHO class IV)), or hepatic disease (e.g., active hepatitis) that in the opinion of the investigator precludes participant's participation in the study.
研究组 & 干预措施
LNP023
Participants receive LNP023 at a dose of 200 mg orally b.i.d
干预措施: Iptacopan (LNP023) (Drug)
结局指标
主要结局
Marginal Proportion (Expressed as Percentage) of Participants With Sustained Increase in Hemoglobin Levels From Baseline of ≥ 2 g/dL in the Absence of Red Blood Cell Transfusions
时间窗: Baseline, hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168
Sustained increase in hemoglobin levels (responder) is defined as an increase from baseline in hemoglobin levels of ≥ 2 g/dL on three out of four measurements between Day 126 and 168 of the core treatment period, without requiring red blood cell (RBC) transfusions between Day 14 and Day 168. Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). The term 'marginal proportion' can be interpreted as the population average probability of being a responder. Results incorporated a method to handle missing data using multiple imputation. Hence, all 40 patients enrolled contributed to the primary analysis.
次要结局
- Marginal Proportion (Expressed as Percentage) With Sustained Hemoglobin Levels of ≥ 12 g/dL in the Absence of Red Blood Cell Transfusions(Hemoglobin between Day 126 and Day 168 and absence of transfusions between Day 14 and Day 168)
- Marginal Proportion (Expressed as Percentage) of Participants Who Remain Free From Transfusions(Between Day 14 and Day 168)
- Change From Baseline in Hemoglobin Levels in the Core Treatment Period(Baseline, Day 126 to 168)
- Percent Change From Baseline in LDH(Baseline, Day 126 to 168)
- Change From Baseline in FACIT-Fatigue Score(Baseline and mean of visits between Day 126 and Day 168)
- Adjusted Annualized Clinical BTH Rate in the Core Treatment Period(Between Day 1 and Day 168)
- Change From Baseline in Absolute Reticulocyte Count(Baseline and mean of visits between Day 126 and 168)
- Adjusted Annualized Major Adverse Vascular Events Rate in the Core Treatment Period(Between Day 1 and Day 168)