A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Sutimlimab in Patients With Primary Cold Agglutinin Disease Without a Recent History of Blood Transfusion
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 42
- 试验地点
- 53
- 主要终点
- Part B: Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)
研究概览
简要总结
The purpose of Part A was to determine whether sutimlimab administration resulted in a greater than or equal to (>=)1.5 grams per deciliter (g/dL) increase in hemoglobin (Hgb) level and avoidance of transfusion in participants with primary cold agglutinin disease (CAD) without a recent history of blood transfusion. The purpose of Part B was to evaluate the long-term safety and tolerability of sutimlimab in participants with primary CAD.
详细描述
The planned total study duration per participant was approximately 1.5 to 2.5 years.
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
- Double (Participant, Investigator)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
BIVV009/BIVV009
Participants with primary CAD and without a recent history of blood transfusion during the last 6 months prior to enrollment in this study, received an intravenous (IV) infusion of BIVV009 6.5 g (for participants less than [<]75 kilograms [kg]) or 7.5 g dose (for participants greater than or equal to [>=]75 kg) on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26), received placebo on Week 26 and continued to receive BIVV009 6.5 or 7.5 g in Part B, every 2 weeks starting at Week 27 for up to an additional 149 weeks (for 6.5 g) or 121 weeks (for 7.5 g). All participants who completed Part A elected to continue in Part B.
干预措施: sutimlimab (BIVV009) (Drug)
Placebo/BIVV009
Participants with primary CAD and without a recent history of blood transfusion during the last 6 months prior to enrollment in this study, received an IV infusion of placebo matched to BIVV009 on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) received BIVV009 6.5 (if <75 kg) or 7.5 g (if >=75 kg) in Part B, on Week 26 and Week 27 and every 2 weeks thereafter for up to an additional 123 weeks (for 6.5 g) or 137 weeks (for 7.5 g). All participants who completed Part A elected to continue in Part B.
干预措施: sutimlimab (BIVV009) (Drug)
Placebo/BIVV009
Participants with primary CAD and without a recent history of blood transfusion during the last 6 months prior to enrollment in this study, received an IV infusion of placebo matched to BIVV009 on Day 0 and Day 7 and every 14 days thereafter in Part A up to Week 25. Participants who completed Part A per protocol through the end of treatment visit (Week 26) received BIVV009 6.5 (if <75 kg) or 7.5 g (if >=75 kg) in Part B, on Week 26 and Week 27 and every 2 weeks thereafter for up to an additional 123 weeks (for 6.5 g) or 137 weeks (for 7.5 g). All participants who completed Part A elected to continue in Part B.
干预措施: placebo (Drug)
结局指标
主要结局
Part B: Number of Participants With Treatment-emergent Adverse Events (AEs) and Serious AEs (SAEs)
时间窗: Part B, 6.5 g cohort: From first dose (Week 26) up to 149 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 184); Part B, 7.5 g cohort: From first dose (Week 26) up to 137 weeks of treatment + 9 weeks of follow-up (i.e., up to Week 172)
Adverse Event (AE): any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Treatment emergent serious adverse events (TESAEs) was defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect, was medically important event. Treatment emergent adverse events (TEAEs): AEs that developed, worsened or became serious during the treatment-emergent (TE) period (from first investigational medicinal product \[IMP\] administration in Part B to last IMP administration + 9 weeks follow-up period).
Part A: Percentage of Participants With Response to Treatment
时间窗: From Week 5 through Week 26
A participant was considered a responder: if he or she did not receive blood transfusion from Week 5 through Week 26 (end of treatment) and did not receive treatment for CAD beyond what was permitted per protocol. Additionally, participant's hemoglobin (Hgb) level must have increased to \>=1.5 grams per deciliter (g/dL) from baseline (defined as last Hgb value before administration of first dose of study drug) at treatment assessment timepoint (defined as average of values from the Week 23, 25, and 26 visits). Percentage of responders was calculated together with 95% exact Clopper-Pearson confidence interval (CI).
次要结局
- Part A: Percentage of Participants With Solicited Symptomatic Anemia at Week 26(Week 26)
- Part B: Change From Baseline in Hemoglobin (Hgb) Level at Each Specified Time Points(Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184))
- Part B: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score (Quality of Life) at Each Specified Time Points(Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 184))
- Part A: Mean Change From Baseline in Lactate Dehydrogenase (LDH) at the Treatment Assessment Timepoint(Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26))
- Part B: Change From Baseline in Total Bilirubin Levels at Each Specified Time Points(Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184))
- Part B: Mean Change From Baseline in Haptoglobin Values at Each Specified Time Points(Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184))
- Part A: Mean Change From Baseline in Hemoglobin (Hgb) Level at the Treatment Assessment Timepoint(Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26))
- Part A: Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score at the Treatment Assessment Timepoint(Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26))
- Part B: Change From Baseline in 12-Item Short-Form Survey (SF-12) Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Each Specified Time Points(Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 184))
- Part B: Mean Change From Baseline in Lactate Dehydrogenase (LDH) Level at Each Specified Time Points(Baseline (Week 0), every 2 weeks starting from Week 27 till Week 175 and at ET/SFU visit (i.e., up to Week 184))
- Part B: Number of Blood Transfusions Per Participant(From Week 27 up to 149 weeks of treatment (i.e., up to Week 176))
- Part B: Number of Healthcare Visits by Type(From Week 27 up to 149 weeks of treatment (i.e., up to Week 176))
- Part B: Change From Baseline in 5-level European Quality of Life 5- Dimensions 5-Level Questionnaire (EQ-5D-5L) Health State Utility Index and VAS Scores at Each Specified Time Points(Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 184))
- Part A: Mean Change From Baseline in Total Bilirubin Levels at the Treatment Assessment Timepoint(Baseline (Week 0), treatment assessment timepoint (i.e., average of Week 23, 25 and 26))
- Part B: Number of Participants With Response to Participant's Global Impression of (Fatigue) Severity (PGIS) Questionnaire at Each Specified Time Points(Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 184))
- Part B: Number of Participants With Response to Participant's Global Impression of Change (PGIC) Questionnaire at Each Specified Time Points(Baseline (Week 0), Weeks 39, 51, 63, 75, 87, 99, 111, 123, 135, 147, 159, 171 and ET Visit/SFU visit (i.e., up to Week 184))