A Phase 2, Multiple Ascending Dose, Randomized, Double-Blind, Placebo-Controlled Study of ALXN1830 Administered Subcutaneously in Patients With Warm Autoimmune Hemolytic Anemia (WAIHA)
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Proportion Of Participants Achieving A ≥ 2 Grams/Deciliter (g/dL) Increase In Hemoglobin (Hgb) From Baseline To The End Of Primary Treatment
研究概览
简要总结
This is a Phase 2, multiple ascending, dose-finding, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety, health-related quality of life, tolerability, pharmacokinetic, pharmacodynamic, and immunogenicity, of up to 3 dose regimens of ALXN1830 administered subcutaneous(ly) (SC) in the treatment of WAIHA.
This study will include 2 randomized, double-blind, placebo-controlled cohorts (Cohorts 1 and 2) to evaluate an 8-week treatment regimen, and an optional third open-label cohort (Cohort 3) to evaluate an alternative 12-week dosing regimen. Participants may continue participation in this study at the participant's and investigator's discretion in an open-label extension (OLE) period, consisting of monthly visits to observe participants for relapse, which will require going back on active treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Cohorts 1 and 2 will be participant and investigator blinded, Cohort 3 will be open label (if initiated).
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
- •Diagnosed with primary or secondary WAIHA at least 6 weeks prior to Screening.
- •Failed or have not tolerated at least one prior WAIHA treatment regimen, for example, corticosteroids, rituximab, azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil, danazol, or vincristine.
- •Hemoglobin < 10 g/dL and ≥ 6 g/dL at Screening.
- •Positive direct antiglobulin test (Coombs) (IgG positive who are positive or negative for the presence of complement C3) at Screening.
- •Evidence of active hemolysis including any one of the below:
- •LDH > upper limit of normal (ULN) or
- •Haptoglobin < lower limit of normal or
- •Indirect bilirubin > ULN
- •Total IgG > 500 mg/dL at Screening
- •Platelet count ≥ 75 x 10^9/liter (L)
- •Absolute neutrophil count greater than 1.0 x 10^9/L
排除标准
- •Participants with Evan's syndrome.
- •Human immunodeficiency virus (HIV) infection (positive HIV 1 or HIV 2 antibody test).
- •Positive hepatitis B surface antigen or hepatitis C antibody test.
- •Inability to travel to the clinic for specified visits during the Primary Treatment Period or fulfill the logistical requirements of study intervention administration.
研究组 & 干预措施
Cohort 1: ALXN1830/Placebo
Participants will be randomized 3:1 to receive ALXN1830 or placebo. Treatment will be received for 8 weeks followed by a follow-up period (no treatment) for 8 weeks. Once complete, participants may continue participation in the study at the participant's and investigator's discretion during the OLE period for up to 2 years inclusive of primary treatment period.
干预措施: ALXN1830 (Drug)
Cohort 1: ALXN1830/Placebo
Participants will be randomized 3:1 to receive ALXN1830 or placebo. Treatment will be received for 8 weeks followed by a follow-up period (no treatment) for 8 weeks. Once complete, participants may continue participation in the study at the participant's and investigator's discretion during the OLE period for up to 2 years inclusive of primary treatment period.
干预措施: Placebo (Drug)
Cohort 2: ALXN1830/Placebo
Participants will be randomized 3:1 to receive ALXN1830 or placebo. Treatment will be received for 8 weeks followed by a follow-up period (no treatment) for 8 weeks. Once complete, participants may continue participation in the study at the participant's and investigator's discretion during the OLE period for up to 2 years inclusive of primary treatment period.
干预措施: ALXN1830 (Drug)
Cohort 2: ALXN1830/Placebo
Participants will be randomized 3:1 to receive ALXN1830 or placebo. Treatment will be received for 8 weeks followed by a follow-up period (no treatment) for 8 weeks. Once complete, participants may continue participation in the study at the participant's and investigator's discretion during the OLE period for up to 2 years inclusive of primary treatment period.
干预措施: Placebo (Drug)
Cohort 3: ALXN1830
If initiated, participants will receive ALXN1830. Treatment will be received for 12 weeks followed by a follow-up period (no treatment) for 8 weeks. Once complete, participants may continue participation in the study at the participant's and investigator's discretion during the OLE period for up to 2 years inclusive of primary treatment period.
干预措施: ALXN1830 (Drug)
结局指标
主要结局
Proportion Of Participants Achieving A ≥ 2 Grams/Deciliter (g/dL) Increase In Hemoglobin (Hgb) From Baseline To The End Of Primary Treatment
时间窗: Baseline through Week 12
Participants will have to achieve this increase without requiring any increase in the dose of an existing WAIHA medication after Day 1 (baseline) and without packed red blood cells (pRBC) transfusions after Day 14.
次要结局
- Change From Baseline Of IgA By Dose Group And Time Point(Up to 2 years)
- Number Of Days To Reach Corticosteroid Discontinuation From The End Of Primary Treatment To The End Of Follow Up After Primary Treatment(Week 12 through Week 20)
- Incidence And Titers Of Neutralizing Antibodies Against ALXN1830 Over Time(Up to 2 years)
- Change From Baseline Of IgG Subtypes (IgG1 4) By Dose Group And Time Point(Up to 2 years)
- Change From Baseline Of Circulating Immune Complexes By Dose Group And Time Point(Up to 2 years)
- Incidence And Titers Of Anti-drug Antibodies Against ALXN1830 Over Time(Up to 2 years)
- Total Number Of Units Of pRBCs Transfused(Baseline through Week 12)
- Number Of Hgb Measurements ≥ 2 g/dL From Baseline To The End Of Primary Treatment(Baseline, Week 12)
- Change From Baseline To The End Of Primary Treatment In Serum Lactate Dehydrogenase (LDH) Levels(Baseline, Week 12)
- Change From Baseline To The End Of Primary Treatment In Serum Indirect Bilirubin(Baseline, Week 12)
- Proportion Of Participants Who Require Any Increase In Corticosteroid Dose From Baseline To The End Of Follow Up After Primary Treatment(Baseline through Week 20)
- Change In Serum Total Immunoglobulin G (IgG) Levels By Dose Group And Time Point(Up to 2 years)
- Time To Hgb Increase By ≥ 2 g/dL From Baseline(Baseline through Week 12)
- Proportion Of Participants Who Require New WAIHA Rescue Medication Or Any Increase In The Dose Of An Existing WAIHA Medication Or pRBC Transfusions For The Treatment Of Anemia(Day 15 through Week 12)
- Change From Baseline To The End Of Primary Treatment In Absolute Reticulocyte Count(Baseline, Week 12)
- Change From Baseline To The End Of Primary Treatment In Serum Haptoglobin(Baseline, Week 12)
- Change In Corticosteroid Dose From The End Of Primary Treatment To The End Of Follow Up(Week 12, Week 20)
- Serum Trough Concentrations Of ALXN1830 Over Time(Up to 2 years)
- Change From Baseline Of Albumin By Dose Group And Time Point(Up to 2 years)
- Proportion Of Participants Achieving A ≥ 2 g/dL Increase In Hgb From Baseline Through Week 4(Baseline through Week 4)
- Total Corticosteroid Usage From Baseline To The End Of Primary Treatment(Baseline, Week 12)
- Number Of Days To Beginning Of Corticosteroid Taper During Follow Up After Primary Treatment(Baseline through Week 20)
- Number Of Days To Corticosteroid Maintenance Dose During Follow Up After Primary Treatment(Baseline through Week 20)
- Change From Baseline Of IgM By Dose Group And Time Point(Up to 2 years)