A Phase 2/3, Multicenter, Randomized, Double-blinded, Placebo-controlled, Repeat-dose Study to Evaluate the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 24
- 主要终点
- Combination Spleen Endpoint: Component 1: Spleen Volume (in MN) at Baseline
研究概览
简要总结
Primary Objective:
The primary objective of this phase 2/3 study was to evaluate the efficacy of olipudase alfa (recombinant human acid sphingomyelinase) administered intravenously once every 2 weeks for 52 weeks in adult participants with acid sphingomyelinase deficiency (ASMD) by assessing changes in: 1) spleen volume as measured by abdominal magnetic resonance imaging (MRI) (and, for the United States [US] only, in association with participant perception related to spleen volume as measured by splenomegaly-related score [SRS]); and 2) infiltrative lung disease as measured by the pulmonary function test, diffusing capacity of the lung for carbon monoxide (DLCO).
Secondary Objectives:
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To confirm the safety of olipudase alfa administered intravenously once every 2 weeks for 52 weeks.
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To characterize the effect of olipudase alfa on the participant perception related to spleen volume as measured by the SRS after 52 weeks of study drug administration. (For the US, the effect of olipudase alfa on the SRS is part of the primary objective).
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To characterize the effect of olipudase alfa after 52 weeks of study drug administration on the following outcome measures assessed sequentially:
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The effect of olipudase alfa on liver volume;
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The effect of olipudase alfa on platelet count;
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The effect of olipudase alfa on fatigue;
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The effect of olipudase alfa on pain;
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The effect of olipudase alfa on dyspnea.
详细描述
The planned total duration per participant was for at least 3 years and up to 5 years and 3 months. This included up to approximately two month of screening, 52 weeks of primary analysis period, up to 4 years and 3 months of extension treatment period, an end-of- study visit within 2 weeks of the last treatment, and a safety follow-up 30 to 37 days after the last treatment.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Placebo
Placebo (saline) administered intravenously once every 2 weeks during the 52 weeks of the primary analysis period for patients randomized to placebo.
干预措施: placebo (saline) (Drug)
Olipudase alfa
Olipudase alfa dose (3 mg/kg body weight) in saline administered intravenously once every 2 weeks during the 52 weeks of the primary analysis period for patients randomized to olipudase alfa, and during the extension treatment period for all patients.
干预措施: Olipudase alfa (Drug)
结局指标
主要结局
Combination Spleen Endpoint: Component 1: Spleen Volume (in MN) at Baseline
时间窗: Baseline (Day 1)
Spleen volume was assessed by abdominal magnetic resonance imaging (MRI) to quantitate the degree of splenomegaly in multiples of normal (MN).
Combination Spleen Endpoint: Component 1: Percent Change From Baseline in Spleen Volume (in MN) at Week 52
时间窗: Baseline, Week 52
Spleen volume was assessed by abdominal MRI to quantitate the degree of splenomegaly in MN.
Percent Change From Baseline in Percent Predicted (% Predicted) Hemoglobin (Hb) and Altitude-Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) at Week 52
时间窗: Baseline, Week 52
Percent predicted Hb and Altitude-adjusted DLco was calculated as: 100\*Adjusted DLco/Predicted DLco in unit of mL CO/min/mmHg where, adjusted DLco = Observed DLco (in mL CO/min/mmHg) times Hemoglobin-adjusted factor times Altitude-adjustment factor.
Combination Spleen Endpoint (Primary for US Only): Component 2: Splenomegaly-Related Score (SRS) at Baseline
时间窗: Baseline (Day 1)
The SRS rates 5 items: abdominal pain, abdominal discomfort, early satiety, dissatisfaction with abdominal body image, and difficulty to bend down using a numerical rating scale of 0 (absent) to 10 (worst imaginable). The total score of SRS ranges from 0 to 50, with higher scores (50) indicated worst imaginable rating. It was pre-specified as secondary endpoint for countries outside of US.
Percent Predicted (% Predicted) Hemoglobin (Hb) and Altitude-Adjusted Diffusing Capacity of the Lung for Carbon Monoxide (DLco) at Baseline
时间窗: Baseline (Day 1)
Percent predicted Hb and Altitude-adjusted DLco was calculated as: 100\*Adjusted DLco/Predicted DLco in unit of mL CO/min/mmHg where, adjusted DLco = Observed DLco (in mL CO/min/mmHg) times Hemoglobin-adjusted factor times Altitude-adjustment factor.
Combination Spleen Endpoint (Primary for US Only): Component 2: Change From Baseline in Splenomegaly-Related Score (SRS) at Week 52
时间窗: Baseline, Week 52
The SRS rates 5 items: abdominal pain, abdominal discomfort, early satiety, dissatisfaction with abdominal body image, and difficulty to bend down using a numerical rating scale of 0 (absent) to 10 (worst imaginable). The total score of SRS ranges from 0 to 50, with higher scores (50) indicated worst imaginable rating. It was pre-specified as secondary endpoint for countries outside of US.
次要结局
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) up to Week 52(From the first infusion of investigational medicinal product (IMP) up to 52 weeks)
- Number of Participants With Adverse Events of Special Interest (AESIs) up to Week 52(From the first infusion of IMP up to 52 weeks)
- Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Liver Function Tests up to Week 52(From Baseline (Day 1) up to 52 weeks)
- Number of Participants Who Developed Anti-Drug Antibodies (ADA) to Olipudase Alfa up to Week 52(Baseline (Day 1) and Week 52)
- Percent Change From Baseline in Liver Volume (in MN) at Week 52(Baseline, Week 52)
- Percent Change From Baseline in Platelet Counts at Week 52(Baseline, Week 52)
- Change From Baseline in Fatigue Severity as Measured by Brief Fatigue Inventory (BFI)-Item 3 Scale Score at Week 52(Baseline, Week 52)
- Change From Baseline in Pain Severity as Measured by Brief Pain Inventory-Short Form (BPI-SF)-Item 3 Scale Score at Week 52(Baseline, Week 52)
- Change From Baseline in Dyspnea Severity as Measured by Functional Assessment of Chronic Illness Therapy (FACIT) Dyspnea Scale at Week 52(Baseline, Week 52)