A Phase 2 Open-Label Proof of Concept Study to Assess the Efficacy, Safety, and Pharmacokinetics of the Oral Factor D (FD) Inhibitor ALXN2050 (ACH-0145228) in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients as Monotherapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 29
- 试验地点
- 1
- 主要终点
- Change From Baseline in Hgb at Week 12
研究概览
简要总结
The study will evaluate the efficacy and safety of the oral Factor D (FD) inhibitor ALXN2050 (ACH-0145228) monotherapy in patients with PNH that are treatment naïve, or patients currently treated with eculizumab who still experience anemia and reticulocytosis, or patients currently treated with ALXN2040 (danicopan) as monotherapy. After signing consent, participants will have periodic visits through Week 12, at which time the primary endpoint and key secondary assessments will be analyzed. Participants will continue on treatment past 12 weeks into a long-term extension portion of the trial.
详细描述
Experimental: Open-label ALXN2050 Monotherapy orally
Group 1: Patients with PNH who are treatment naïve
Group 2: Patients with PNH who have received complement component 5 (C5) inhibition with eculizumab for at least 6 months, who continue to experience anemia and reticulocytes above the upper limit of normal (ULN) who will switch to ALXN2050 monotherapy
Group 3: Patients with PNH receiving danicopan monotherapy in study ACH471-103 will switch to ALXN2050 monotherapy
After signing the informed consent form, participants will enter the screening period. During the Screening Period, eligibility and screening assessments will be performed. Screening assessments may be spread over more than one visit if necessary. At the baseline visit, screened participants who continue to meet eligibility criteria will enter the Treatment Period.
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
- •Diagnosis of PNH.
- •Male or female, ≥ 18 years of age
- •Eligibility Criteria:
- •Eligibility Criteria Specific for Group 1:
- •PNH Patients who have no history of treatment with any complement inhibitor at any dose.
- •PNH Type III erythrocyte or granulocyte clone size ≥10%
- •Absolute reticulocyte count ≥100×10^9/liter [L].
- •Anemia (Hgb <10.5 grams/deciliter [g/dL]).
- •LDH ≥1.5× upper limit of normal.
- •Platelet count ≥30,000/microliter (µL)
- •Absolute neutrophil count (ANC) ≥750/ µL.
- •Eligibility Criteria Specific for Group 2:
- •Stable background regimen of at least 24 weeks for eculizumab without change in dose or interval for at least the past 8 weeks
- •Anemia (Hgb <10 g/dL)
- •Absolute reticulocyte count ≥100×10^9/L
- •Platelet count ≥30,000/µL
- •Absolute neurophil count (ANC) ≥750/ µL
- •Eligibility Criteria Specific for Group 3:
- •Patient received danicopan during Study ACH471-103
排除标准
- •History of a major organ transplant or hematopoietic stem cell/marrow transplant .
- •Known aplastic anemia or other bone marrow failure that requires HSCT, or if these patients are on immunosuppressive agents for less than 24 weeks.
- •Known underlying bleeding disorders or any other conditions leading to anemia not primarily associated with PNH.
- •Estimated glomerular filtration rate <30 milliliters/minute/1.73 meters squared and/or are on dialysis.
研究组 & 干预措施
Open-label ALXN2050 Monotherapy
Experimental: Open-label ALXN2050 Monotherapy ALXN2050 orally administered
Group 1: Patients with PNH who are treatment naïve
Group 2: Patient with PNH who have received complement component 5 (C5) inhibition with eculizumab for at least 6 months, who continue to experience anemia and reticulocytes above the upper limit of normal (ULN)
Group 3: Patients with PNH who have received danicopan monotherapy during study ACH471-103
干预措施: ALXN2050 (Drug)
结局指标
主要结局
Change From Baseline in Hgb at Week 12
时间窗: Baseline, Week 12
Hgb baseline was defined as the lowest Hgb value observed between and including screening and first dose date. To address the impact of transfusion, Hgb values collected within 4 weeks after transfusion were not included in the primary efficacy analysis. Change from Baseline = Hgb at Week 12 - Baseline Hgb.
次要结局
- Number of Participants Who Had Transfusion Avoidance During 12 Weeks of Treatment With ALXN2050(Baseline up to Week 12)
- Number of Red Blood Cell (RBC) Units Transfused During 12 Weeks of Treatment(Baseline up to Week 12)
- Number of Transfusion Instances During 12 Weeks of Treatment(Baseline up to Week 12)
- Change From Baseline in Lactate Dehydrogenase (LDH) at Week 12(Baseline, Week 12)
- Change From Baseline in Absolute Reticulocyte Count at Week 12(Baseline, Week 12)
- Change From Baseline in Direct and Total Bilirubin at Week 12(Baseline, Week 12)
- Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clone Size at Week 12(Baseline, Week 12)
- Change From Baseline in Component 3 (C3) Fragment Deposition on PNH RBCs at Week 12(Baseline, Week 12)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Events Leading to Discontinuation of Study Medication(From first dose of study drug up to Week 217)
- Change From Baseline in Hgb at the End of Treatment (EOT) During the LTE Period(Baseline, EOT visit (Maximum exposure: 213.4 weeks))
- Change From Baseline in LDH at the EOT During the LTE Period(Baseline, EOT visit (Maximum exposure: 213.4 weeks))
- Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Scale (Version 4) Total Score at Week 12(Baseline, Week 12)
- Change From Baseline in FACIT-Fatigue Scale (Version 4) Total Score at the EOT During the LTE Period(Baseline, EOT visit (Maximum exposure: 213.4 weeks))