A Multicenter, Single Arm, Open-label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily Iptacopan in Adult PNH Patients Who Have Hb≥10 g/dL in Response to Anti-C5 Antibody and Switch to Iptacopan
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 30
- 主要终点
- Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Non-inferiority
研究概览
简要总结
The purpose of the study was to find out if iptacopan is effective and safe in adult patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) who switched from their current standard of care treatment (eculizumab or ravulizumab) to study treatment, iptacopan/LNP023.
详细描述
This was a multicenter, single-arm, open label trial, with iptacopan treatment for 24 weeks in adult PNH patients.
This study was comprised of two periods:
- A Screening period lasting up to 8 weeks.
- A 24-week open-label, iptacopan Treatment period.
After completion of the treatment period, participants who continued to benefit from the iptacopan treatment based on the study doctor's evaluation were able to join the Roll-over extension study (CLNP023C12001B).
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent must be obtained prior to participation in the study.
- •Male and female participants ≥ 18 years of age, at the time of ICF signatures and with a diagnosis of PNH confirmed by treating physician.
- •Stable regimen (dose and intervals) of anti-C5 antibody treatment (either eculizumab or ravulizumab) for at least 6 months prior to screening
- •Mean hemoglobin level ≥10 g/dL
- •Vaccination against Neisseria meningitidis and S. pneumoniae infection are required prior to the start of iptacopan treatment.
- •If not received previously, vaccination against Haemophilus influenzae infections is recommended, if available and according to local regulations.
- •Ability to communicate well with the investigator, to understand and comply with the requirements of the study
- •Other protocol -defined inclusion criteria may apply at the end.
排除标准
- •Participation in any other investigational drug trial or use of other investigational drugs at the time of enrollment
- •Patients requiring red blood cell transfusion in the 6 months prior to screening or during screening
- •History of stem cell transplantation or any solid organ transplantation
- •Active systemic bacterial, viral (incl. COVID-19) or fungal infection within 14 days prior to study drug administration
- •Presence of fever ≥ 38.0 °C (100.4 °F) within 7 days prior to study drug administration
- •Human immunodeficiency virus (HIV) infection (known history of HIV or test positive for HIV antibody at Screening)
- •A history of recurrent invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus
- •Unstable medical condition including, but not limited to, myocardial ischemia, active gastrointestinal bleeding, coexisting chronic anemia unrelated to PNH, or unstable thrombotic event not amenable to active treatment as judged by the investigator at Screening.
- •History of cancer of any part of the body within the past 5 years,
- •Ongoing drug or alcohol abuse that could interfere with patient's participation in the trial.
- •Any medical condition deemed likely to interfere with the patient's participation in the study
- •Female patients who are pregnant or breastfeeding, or intending to conceive during the course of the study
研究组 & 干预措施
LNP023 200mg b.i.d.
Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally
干预措施: Iptacopan (Drug)
结局指标
主要结局
Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Non-inferiority
时间窗: Baseline, Day 126 to Day 168
Change in hemoglobin (Hb) levels as mean of visits between Day 126 and Day 168 compared to baseline. Baseline is defined as as the mean of three Hb assessments conducted at the central laboratory: two during screening and the third on Day 1. The estimation of change from baseline in Hb levels was handled by the hypothetical strategy where participants were assumed as if they did not receive RBC transfusions while on treatment (RBC transfusions were expected to be rare). Assuming that participants had stable Hb levels at study entry, the mean change from baseline in Hb level between Day 126 and Day 168 was expected to be unchanged should participants have continued on anti-C5 treatment. Non-inferiority of iptacopan was therefore tested by the null hypothesis (H0) against the alternate hypothesis (H1) comparing the mean change from baseline in Hb level in iptacopan between Day 126 and Day 168 (μ) to -1 g/dL: H0: μ \<= -1, H1: μ \> -1.
次要结局
- Change in Hb Levels as Mean of Visits Between Day 126 and Day 168 Compared to Baseline Tested for Superiority(Baseline, Day 126 to Day 168)
- Proportion of Hematological Responders to Iptacopan Treatment(Day 126 to Day 168)
- Proportion of Participants Who Remain Free From Transfusions(Day 1 to Day 168)
- Change From Baseline in Absolute Reticulocytes Count (ARC) Levels(Baseline, Day 126 to Day 168)
- Percentage Change From Baseline in Lactate Dehydrogenase (LDH) Levels(Baseline, Day 126 to Day 168)
- Change From Baseline in Treatment Satisfaction Score Using TSQM-9 Questionnaire(Baseline, Day 84 and Day 168)
- Change From Baseline in Fatigue Score Using FACIT-F Questionnaire(Baseline, Day 84 and Day 168)
- Percentage of Patients Who Had Major Adverse Vascular Events (MAVEs)(Up to 168 Days)
- Percentage of Patients Who Had Breakthrough Hemolysis (BTH) Event(Up to 168 Days)