A Randomized, Open-Label, Multicenter, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of Oral BCX9930 Monotherapy for the Treatment of Paroxysmal Nocturnal Hemoglobinuria in Subjects With Inadequate Response to C5 Inhibitor Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Part 1: Change From Baseline in Hemoglobin at Week 24
研究概览
简要总结
The purpose of this study was to determine the efficacy and safety of BCX9930 monotherapy for the treatment of PNH compared to continued C5 inhibitor therapy in adult PNH participants with residual anemia despite treatment with a C5 inhibitor.
详细描述
This was a randomized, active comparator-controlled, open-label, parallel-group, 2-part study. Parts 1 and 2 were conducted in the same participants.
Part 1 of the study was designed to evaluate the efficacy, safety, and tolerability of oral BCX9930 monotherapy for 24 weeks versus continuing C5 inhibitor therapy in participants with PNH with inadequate response to their current C5 inhibitor therapy. Participants were randomized to either discontinue C5 inhibitor therapy and start BCX9930 monotherapy or to continue C5 inhibitor therapy for the 24-week randomized treatment period. The primary efficacy and safety analyses were based on Part 1.
Part 2 of the study was designed to evaluate the long-term safety, tolerability, and effectiveness of BCX9930 monotherapy when administered through Week 52. All participants in Part 2 received BCX9930. Participants who were randomized to BCX9930 monotherapy in Part 1 continued to receive BCX9930 in Part 2. Participants who were randomized to C5 inhibitor therapy in Part 1 discontinued that therapy at the Week 24 visit and received BCX9930 in Part 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Male or female, aged ≥ 18 years old
- •Body weight ≥ 40 kg
- •Documented diagnosis of PNH
- •Currently being treated with a stable C5 inhibitor regimen
- •Documentation of current vaccinations against Neisseria meningitidis and Streptococcus pneumoniae or willing to start vaccination series
- •At screening: PNH clone size of ≥ 10% and hemoglobin ≤ 10.5 g/dL
排除标准
- •Known history of or existing diagnosis of hereditary complement deficiency
- •History of hematopoietic cell transplant or solid organ transplant or anticipated candidate for transplantation
- •Myocardial infarction or cerebrovascular accident within 30 days prior to screening, or current and uncontrolled clinically significant cardiovascular or cerebrovascular condition
- •History of malignancy within 5 years prior to the screening visit
- •Active bacterial, viral, or fungal infection or any other serious infection within 14 days prior to screening
- •Treatment with anti-thymocyte globulin within 180 days prior to screening
- •Initiation of treatment with an erythrocyte or platelet growth factor, or danazol within 28 days prior to screening
- •Receiving iron supplementation with an unstable dose in the 28 days prior to screening
研究组 & 干预措施
BCX9930/BCX9930
Participants were randomized to receive BCX9930 during Part 1 and continued to receive the same during Part 2. Per protocol amendment, participants who previously received 500 mg twice daily (BID) and remained on study treatment were dose adjusted to 400 mg BID. For all newly enrolled participants, at the initiation of BCX9930 dosing, participants were administered a dose of 200 mg BID for the first 14 days of treatment before increasing to 400 mg BID. The maximum treatment duration on BCX9930 in Part 1 was 24 weeks. The overall maximum treatment duration on BCX9930 was 377 days.
干预措施: BCX9930 (Drug)
C5-Inhibitor (C5-INH)/BCX9930
Participants randomized to this group continued the existing C5-INH therapy during Part 1. After the sponsor decided to halt enrolment in the study permanently and terminate the study, participants entered Part 2 where they switched to open-label BCX9930 monotherapy prior to Week 24, if earlier. The maximum treatment duration on C5-INH in Part 1 was 24 weeks. The maximum treatment duration on BCX9930 was 197 days.
干预措施: Eculizumab (Drug)
C5-Inhibitor (C5-INH)/BCX9930
Participants randomized to this group continued the existing C5-INH therapy during Part 1. After the sponsor decided to halt enrolment in the study permanently and terminate the study, participants entered Part 2 where they switched to open-label BCX9930 monotherapy prior to Week 24, if earlier. The maximum treatment duration on C5-INH in Part 1 was 24 weeks. The maximum treatment duration on BCX9930 was 197 days.
干预措施: Ravulizumab (Drug)
C5-Inhibitor (C5-INH)/BCX9930
Participants randomized to this group continued the existing C5-INH therapy during Part 1. After the sponsor decided to halt enrolment in the study permanently and terminate the study, participants entered Part 2 where they switched to open-label BCX9930 monotherapy prior to Week 24, if earlier. The maximum treatment duration on C5-INH in Part 1 was 24 weeks. The maximum treatment duration on BCX9930 was 197 days.
干预措施: BCX9930 (Drug)
结局指标
主要结局
Part 1: Change From Baseline in Hemoglobin at Week 24
时间窗: Baseline, Week 24
次要结局
- Part 1: Number of Participants Who Were Transfusion-free(From Week 4 to Week 24)
- Part 1: Number of Units of pRBCs Transfused(From Week 4 to Week 24)
- Part 1: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score(Baseline, Week 24)
- Part 1: Percent Change From Baseline in Lactate Dehydrogenase(Baseline, Week 24)
- Part 1: Percentage (%) Reduction in the Rate of pRBC Units Transfused(Prestudy (12 months prior to screening) and from Week 4 to Week 24)
- Part 1: Number of Participants With Hemoglobin ≥ 12 Grams Per Deciliter (g/dL)(Week 24)
- Part 1: Number of Participants Who Achieved Hemoglobin Stabilization(From Week 4 to Week 24)
- Part 1: Change From Baseline in Complement Component 3 (C3)-Opsonized Red Blood Cells (RBCs)(Baseline, Week 24)
- Part 1: Change From Baseline in Total Paroxysmal Nocturnal Hemoglobinuria (PNH) RBC Clone Size(Baseline, Week 24)
- Part 1: Change From Baseline in Ratio of Total PNH RBC Clone Size to PNH White Blood Cell (WBC) Clone Size(Baseline, Week 24)
- Part 1: Change From Baseline in Absolute Reticulocyte Count (ARC)(Baseline, Week 24)
- Part 1: Number of Participants With ARC in the Normal Range(Week 24)
- Part 1: Change From Baseline in Haptoglobin(Baseline, Week 24)
- Part 1: Number of Participants With Haptoglobin ≥ Lower Limit of Normal (LLN) Reference Range(Week 24)
- Part 1: Change From Baseline in Total Bilirubin(Baseline, Week 24)