An Open-label, Single-arm, Multicenter, Phase 3 Study to Assess Pharmacokinetics, Safety and Tolerability of Iptacopan in Pediatric PNH Patients 2 to <18 Years of Age
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 17
- 主要终点
- Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The purpose of this open-label, single arm, multicenter, phase 3 study is to assess the pharmacokinetics of iptacopan in pediatric patients and to assess whether iptacopan is safe and well tolerated when used for the treatment of pediatric paroxysmal nocturnal hemoglobinuria (PNH) patients 2 to < 18 years of age.
详细描述
This is a multicenter, open-label, single arm study comprised of an up to a 8-week Screening Period, and a 26-week Treatment Period followed by a 26-week Extension Treatment Period.
This study will enroll a minimum of 12 pediatric patients 2 to < 18 years of age in a staggered manner into 3 cohorts: Cohort 1 (adolescents 12 to < 18 years of age, approximately 6 patients), Cohort 2a (6 to < 12 years of age, approximately 4 patients), and Cohort 2b (2 to < 6 years of age, approximately 2 patients).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female participants 2 to < 18 years of age with a diagnosis of PNH confirmed by high-sensitivity flow cytometry with red blood cells (RBCs) and with white blood cells granulocytes/monocytes clone size ≥ 10%. The minimum body weight for patients in Cohort 1 is 35 kg.
- •Patients being treated with anti-C5 therapy and who have been on a stable regimen (dose and interval) for at least 6 months prior to enrollment, may be screened and enrolled in the study and switched to iptacopan irrespective of their anemia and hemolysis status, at the discretion of the Principal Investigator.
- •Patients who are anti-C5 treatment naive: mean hemoglobin level < 10 g/dL confirmed by central laboratory assessment during screening.
- •Patients who are anti-C5 treatment naive: lactate dehydrogenase (LDH) > 1.5 × upper limit of normal (ULN) documented by at least 2 laboratory measurements 2 to 6 weeks apart during the screening period, one of which is to be done by the central lab.
- •Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infection is required prior to the start of study treatment. If the participant has not been previously vaccinated, or if a booster is required, vaccine should be given according to local guidelines at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post-vaccination, prophylactic antibiotic treatment should be initiated.
- •Vaccination against Haemophilus influenzae is recommended, according to local guidelines, at least 2 weeks before iptacopan.
排除标准
- •History of hypersensitivity to the study drug or its excipients or to drugs of similar chemical classes.
- •Known or suspected hereditary complement deficiency at screening.
- •History of hematopoietic stem cell transplantation (HSCT) or scheduled for HSCT within 52 weeks from enrollment into the study (Day 1).
- •Patients with laboratory evidence of bone marrow failure (reticulocytes < 100 x 10 to the ninth/L; platelets < 30 × 10 to the ninth/L; neutrophils < 0.5 × 10 to the ninth/L).
- •Active systemic bacterial, viral (including COVID-19), or fungal infection within 14 days prior to study drug administration.
- •Presence of fever ≥ 38 °C (100.4 °F) within 7 days prior to study drug administration.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
LNP023-Cohort 1 (12 < 18 years old)
Participants (12 to < 18 years old) will take iptacopan at the dose of 200 mg twice per day (in the morning and in the evening).
干预措施: LNP023 (Drug)
LNP023 -Cohort 2 (2 to < 12 years old)
Participants (2 to < 12 years old) will be dosed based on weight at the Day 1 visit, initially. The study medication dose will be reassessed and re-adjusted as needed based on their weight at Week 12, 26, and 38.
干预措施: LNP023 (Drug)
结局指标
主要结局
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: 26 weeks
Incidence and severity of AEs and SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs) and laboratory results qualifying and reported as AEs.
PK parameter (Cmax)
时间窗: Week 2
Cmax is defined as the maximum (peak) observed concentration following a dose.
PK parameter (AUClast)
时间窗: Week 2
AUClast is the area under the plasma concentration-time curve from time zero to the time of last quantifiable concentration (tlast).
PK parameter (AUCtau)
时间窗: Week 2
AUCtau describes the area under the curve limited to the end of a dosing interval.
PK parameter (Ctrough)
时间窗: Weeks 2, 4, 12 and 26
Ctrough is the observed plasma concentration that is just prior to the beginning of, or at the end of a dosing interval.
次要结局
- Change in hemoglobin (Hb) from baseline ≥1 g/dL (in the absence of RBC transfusions from Day 14).(Baseline, Week 26, Week 52)
- Change in Hb from baseline ≥2 g/dL (in the absence of RBC transfusions from Day 14).(Baseline, Week 26, Week 52)
- Normal Hb in the absence of red blood cell (RBC) transfusions from Day 14.(Week 26 and Week 52)
- Absence of packed-RBC transfusions and not meeting transfusion criteria from Day 14 at Week 26 and Week 52(Week 26 and Week 52)
- Change from baseline in hemoglobin(Baseline, Week 26, Week 52)
- Change from baseline in lactate dehydrogenase (LDH)(Baseline, Week 26, Week 52)