A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Subjects With Amyotrophic Lateral Sclerosis (ALS)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 249
- 试验地点
- 60
- 主要终点
- RTP: Combined Assessment of Function and Survival (CAFS) Rank Score (Joint-Rank Score) at Week 52
研究概览
简要总结
This is a 24-month, Phase 2, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of pegcetacoplan in subjects with amyotrophic lateral sclerosis (ALS)
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
- 否
入选标准
- •At least 18 years of age
- •Sporadic ALS diagnosed as definite, probable, or laboratory-supported probable as defined by the revised El Escorial criteria
- •Slow vital capacity (SVC) ≥60% of the predicted value at screening
- •Onset of ALS symptoms within 72 weeks (18 months) prior to screening
- •Total ALSFRS-R score of ≥30 at screening
- •Have vaccination within 5 years against Streptococcus pneumoniae, Neisseria meningitidis (types A, C, W, Y, and B), and Haemophilus influenzae (type B) or agree to receive vaccination
排除标准
- •Confirmed or suspected other causes of neuromuscular weakness
- •Diagnosed with another neurodegenerative disease (examples include Parkinson's disease and Huntington's disease)
- •Significant pulmonary disorder not attributed to ALS (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, cystic fibrosis, pulmonary arterial hypertension)
- •If taking riluzole, participant must be on a stable dose for 30 days prior to the start of the screening period. Use of riluzole is not required for participation.
- •If taking edaravone, participant must be on a stable dose for 60 days prior to the start of the screening period. Use of edaravone is not required for participation.
- •Participation in any other investigational drug trial or exposure to other investigational agent, device, or procedure within 30 days or within 5-half lives of the treatment (whichever is longer) prior to the start of the screening period or during study participation
- •Use of any other complement inhibitor within 30 days or within 5-half lives of the treatment (whichever is longer) prior to the start of the screening period or during study participation
研究组 & 干预措施
1,080 mg pegcetacoplan (APL-2)
administered subcutaneously twice weekly
干预措施: Pegcetacoplan (APL-2) (Drug)
Placebo administered subcutaneously twice weekly
干预措施: Placebo (Other)
结局指标
主要结局
RTP: Combined Assessment of Function and Survival (CAFS) Rank Score (Joint-Rank Score) at Week 52
时间窗: Week 52
The CAFS scale is a combined endpoint ranking subjects' clinical outcomes based on ALS Functional Rating Scale-Revised (ALSFRS-R-described below) and survival time. For ALSFRS-R, 12 functions were rated on 5-point ordinal rating scales (0 to 4) with a total score range of 0-48 (sum of all 12 items); higher score indicated better functioning. For survival time, longer the subject survives indicated better outcome. Each subject's outcome was compared to every other subject outcome in trial in series of pairwise comparisons, summed scores (sum of comparisons \[+1 {better}, 0 {tie}, -1 {worse}\]) were ranked and ranged from 001-247 (number of subjects in modified \[m\]ITT population).Reported values are the least squares mean rank scores in each group for the composite endpoint. Higher rank indicated better outcome.
RTP: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
时间窗: From first dose of study drug (Day 1) up to 56 days post last dose of study drug, approximately 60 weeks
An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An SAE was any AE or suspected adverse reaction that, in the view of the investigator, resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or was a congenital anomaly or birth defect. TEAEs were AEs that started on or after first dose of study drug or started before first dose of study drug but increased in severity on or after the first dose of study drug up to 56 days post last dose of study drug.
OLP: Number of Participants With Treatment-emergent Adverse Events and Treatment-emergent Serious Adverse Events
时间窗: From first dose of study drug (Week 52) up to 56 days post last dose of study drug, approximately 60 weeks
An AE was any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug related. An SAE was any AE or suspected adverse reaction that, in the view of the investigator, resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or was a congenital anomaly or birth defect. TEAEs were AEs that started on or after first dose of study drug or started before first dose of study drug but increased in severity on or after the first dose of study drug up to 56 days post last dose of study drug.
RTP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale (C-SSRS) up to Week 52
时间窗: Baseline (Day 1) up to Week 52
The C-SSRS is a measure used to identify and assess individuals at risk for suicide and included "yes" or "no" responses for assessment of suicidal ideation (SI) and suicidal behavior (SB).C-SSRS SI items are classified on 5-item scale:1 (wish to be dead),2 (non-specific active suicidal thoughts),3 (active SI with any methods without intent to act),4 (active SI with some intent to act, without specific plan) and 5 (active SI with a specific plan and intent).C-SSRS SB items are classified on 5-item scale: 1 (preparatory acts or behavior), 2 (aborted attempt), 3 (interrupted attempt), 4 (actual attempt \[non-fatal\]) and 5 (completed suicide). Numeric ratings were provided for SI (1 to 5) and SB (1 to 5) with 5 being more severe for each. Number of subjects with a response of 'yes' to SI only, SB only \& SI and SB are reported. Baseline: last available, non-missing observation prior to first study drug administration.
OLP: Number of Subjects With Positive Response to Columbia-Suicide Severity Rating Scale up to Week 104
时间窗: From Baseline (Week 52) up to Week 104
The C-SSRS is a measure used to identify and assess individuals at risk for suicide and included "yes" or "no" responses for assessment of SI and SB.C-SSRS SI items are classified on 5-item scale:1 (wish to be dead),2 (non-specific active suicidal thoughts),3 (active SI with any methods without intent to act),4 (active SI with some intent to act, without specific plan) and 5 (active SI with a specific plan and intent).C-SSRS SB items are classified on 5-item scale:1 (preparatory acts or behavior),2 (aborted attempt), 3 (interrupted attempt), 4 (actual attempt \[non-fatal\]) and 5 (completed suicide). Numeric ratings were provided for SI (1 to 5) and SB (1 to 5) with 5 being more severe for each. Number of subjects with a response of 'yes' to SI only, SB only \& SI and SB are reported. Baseline: last available, non-missing observation prior to first study drug administration in OLP.
次要结局
- RTP: Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) Score at Week 52(Baseline (Day 1) and Week 52)
- RTP: Change From Baseline in Percent Predicted Slow Vital Capacity (%SVC) at Week 52(Baseline (Day 1) and Week 52)
- RTP: Change From Baseline in Muscle Strength at Week 52(Baseline (Day 1) and Week 52)
- RTP: Number of Subjects With an Event of Death or Permanent Tracheostomy or Permanent Assisted Ventilation at Week 52(Baseline (Day 1) up to Week 52)
- RTP: Change From Baseline in ALS Assessment Questionnaire (ALSAQ)-40 at Week 52(Baseline (Day 1) and Week 52)
- OLP: Change From Baseline in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised Score at Week 104(Baseline (Week 52) and Week 104)
- OLP: Change From Baseline in Percent Predicted Slow Vital Capacity at Week 104(Baseline (Week 52) and Week 104)
- OLP: Change From Baseline in Muscle Strength at Week 104(Baseline (Week 52) and Week 104)
- OLP: Number of Subjects With an Event of Death or Permanent Tracheostomy or Permanent Assisted Ventilation at Week 104(Baseline (Week 52) and Week 104)
- OLP: Change From Baseline in ALS Assessment Questionnaire-40 at Week 104(Baseline (Week 52) and Week 104)
- Number of Subjects With an Event of Death During the Study(RTP: Baseline (Day 1) up to Week 52; OLP: Baseline (Week 52) up to Week 104)