A Multicenter, Single-arm, Open Label Trial to Evaluate Efficacy and Safety of Oral, Twice Daily LNP023 in Adult aHUS 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
- 34
- 试验地点
- 54
- 主要终点
- Percentage of participants with complete TMA response without the use of PE/PI and anti-C5 antibody
研究概览
简要总结
The purpose of this Phase 3 study is to determine whether iptacopan (LNP023) is efficacious and safe for the treatment of aHUS in adult patients who are treatment naive to complement inhibitor therapy.
详细描述
The study is designed as a multicenter, single-arm, open label study to demonstrate the efficacy and safety of LNP023 (iptacopan) at a dose of 200 mg b.i.d. in adult patients with aHUS who are treatment naive to complement inhibitor therapy (including anti-C5 antibody). The study will enroll approximately 50 participants and assess the effects of iptacopan on a range of efficacy assessments relevant to aHUS including hematological and kidney parameters, dialysis requirement, changes in chronic kidney disease (CKD) stage, as well as patient reported outcomes (PRO) for fatigue and quality of life.
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
盲法说明
Open label single arm study
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
- •Main Inclusion Criteria:
- •Adult patients with evidence of active thrombotic microangiopathy (TMA), including thrombocytopenia, evidence of hemolysis, and acute kidney injury
- •Vaccinations against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections are required prior to the start of study treatment. If the patient has not been previously vaccinated, or if a booster is required, vaccine should be given according to local regulations, at least 2 weeks prior to first study drug administration. If study treatment has to start earlier than 2 weeks post vaccination or before vaccination is given, prophylactic antibiotic treatment must be administered at the start of study treatment and for at least 2 weeks after vaccination
排除标准
- •Treatment with complement inhibitors, including anti-C5 antibody
- •ADAMTS13 deficiency (<10% activity or <0.1U/ml), and/or Shiga toxin-related hemolytic uremic syndrome (STx-HUS), and/or Positive direct Coombs test
- •Identified drug exposure-related HUS or HUS related to known genetic defects of cobalamin C metabolism or known diacylglycerol kinase ε (DGKE) mediated aHUS
- •Receiving PE/PI, for 14 days or longer, prior to the start of screening for the current TMA
- •Bone marrow transplantation (BMT)/hematopoietic stem cell transplantation (HSCT), heart, lung, small bowel, pancreas, or liver transplantation
- •Patients with sepsis or active severe systemic bacterial, viral (including COVID-19) or fungal infection, systemic infection which confounds an accurate diagnosis of aHUS or impedes the ability to manage the aHUS disease, active infection (or history of recurrent invasive infections) caused by encapsulated bacteria
- •Kidney disease suggestive of other disease than aHUS or of chronic kidney failure or family history of non-complement mediated genetic kidney disease
- •Liver disease or liver injury at screening
- •Systemic sclerosis (scleroderma), systemic lupus erythematosus (SLE), or antiphospholipid antibody positivity or syndrome
- •Chronic hemo- or peritoneal dialysis
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Iptacopan 200 mg b.i.d
Single arm open-label with 50 adult patients receiving 200mg oral twice daily doses of iptacopan
干预措施: Iptacopan (Drug)
结局指标
主要结局
Percentage of participants with complete TMA response without the use of PE/PI and anti-C5 antibody
时间窗: 26 weeks of study treatment
The number/percentage of participants treated with iptacopan achieving complete thrombotic microangiopathy (TMA) response during 26 weeks of study treatment. Complete TMA Response is defined as (1) hematological normalization in platelet count (platelet count ≥150 x 10\^9/L) and LDH (below ULN), and (2) improvement in kidney function (≥ 25% serum creatinine reduction from baseline), maintained for two measurements obtained at least four weeks apart, and any measurement in between
Long term safety and efficacy evaluations
时间窗: 52 weeks of study treatment
Long term (one year) safety, tolerability and efficacy of iptacopan via 1) safety evaluations including adverse events/serious adverse events, safety laboratory parameters, vital signs etc. after 52 weeks of study treatment, and 2) efficacy evaluations including complete TMA response, hematological parameters (platelets, LDH, hemoglobin), eGFR, PROs after 52 weeks of study treatment
次要结局
- Time to achieve complete TMA response(26 weeks of study treatment)
- Percentage of participants with increase from baseline in hemoglobin levels ≥ 2 g/dL(26 weeks of study treatment)
- Change from baseline on hematologic parameters(At week 26)
- Change from baseline on estimated glomerular filtration rate(At week 26)
- Change from baseline in chronic kidney disease (CKD) stage(At week 26)
- Change from baseline in patient-reported outcomes score as measured by the Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Questionnaire(At week 26)
- Change from baseline in patient-reported outcomes score as measured by the EuroQol 5-level EQ-5D version (EQ-5D-5L) Questionnaire(At Week 26)
- Change from baseline in patient-reported outcomes score as measured by the Patient Global Impression of Severity (PGIS) questionnaire(At Week 26)
- Percentage of participants on dialysis(26 weeks of study treatment)
- Change from baseline in patient-reported outcomes score as measured by the Short-form 36 health survey questionnaire version 2 (SF-36 v2)(At Week 26)