NCT05039099已完成2 期
A Phase 2a, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety, Tolerability, Pharmacodynamic Markers, and Pharmacokinetics of AP-101 in Patients With Familial Amyotrophic Lateral Sclerosis (fALS) and Sporadic Amyotrophic Lateral Sclerosis (sALS)
AL-S Pharma13 个研究点 分布在 6 个国家目标入组 73 人开始时间: 2021年9月2日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 73
- 试验地点
- 13
- 主要终点
- Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, PK, and PD of AP-101 in participants with fALS and sALS.
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
- •All participants must adhere to contraception restrictions
- •Female participants of childbearing potential must adhere to contraception restrictions
- •Have possible, clinically probable, clinically probable-laboratory supported or definite familial or sporadic ALS in accordance with the El-Escorial criteria or who have a diagnosis of ALS as defined by the Gold Coast Criteria; progressive motor impairment documented by history or repeated clinical examination, preceded by normal motor development, and presence of upper and lower motor neuron dysfunction in at least 1 body region or lower motor neuron dysfunction in at least 2 body regions and investigations excluding other conditions
- •In familial ALS participants, a confirmed pathogenic superoxide dismutase 1 (SOD1) mutation
- •Onset of symptoms (i.e, weakness) within past 24 months prior to screening, at the time of obtaining informed consent
- •Have slow vital capacity (SVC) of greater than or equal to (> or =) 50 percentage (%) of predicted values. Participants with SVC of <50% of predicted values may be permitted to enter the open-label extension, based on the opinion of the investigator
- •Absence of bilevel positive airway pressure (BiPAP)/proportional assist ventilation (PAV) > 4 hours for symptoms attributable to ALS. Use of a CPAP for pre-existing conditions will be allowed
- •If on riluzole, must be on a stable dose.
- •If on edaravone, must have completed 2 cycles and are expected to remain on the same dose throughout the study
- •Able to provide informed consent which includes compliance with the requirements and restrictions
- •Have venous access sufficient to allow for blood sampling
- •Have clinical laboratory test results within the normal reference range for the population or study site, or results with acceptable deviations that are judged to be not clinically significant by the investigator
排除标准
- •Have participated or currently participating in another clinical trial within 12 weeks of baseline (Day 1)
- •Have undergone a tracheostomy for ALS symptoms
- •Are on nasal intermittent positive pressure ventilation (NIPPV) >4 hours per day for the treatment of ALS related symptoms
- •Have other causes of neuromuscular weakness
- •Have cognitive impairment, severe disease in the cardiovascular, hematological, renal system, neurodegenerative disease, pulmonary disorder, or psychiatric illness
- •Pregnant or nursing women
- •Have been exposed to any antisense treatment targeting SOD1 within 6 months of the baseline visit
- •Have undergone stem cell therapy
研究组 & 干预措施
AP-101
Experimental
AP-101 is administered by IV.
干预措施: AP-101 (Drug)
Placebo
Placebo Comparator
Placebo is administered by IV.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
时间窗: From start of the study up to Week 51
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with the study intervention. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, other situations.
Number of Participants with Abnormalities in Vital Signs, Clinical Laboratory Assessments, Physical and Neurological Examinations, Electrocardiograms (ECGs)
时间窗: From start of the study up to Week 51
次要结局
- Change From Baseline in Neurofilament Light Chain and Phospho-Neurofilament Heavy Chain Levels in Plasma up to Week 51(Baseline, up to Week 51)
- Elimination half-life (t1/2) of AP-101 in Serum(Predose up to Week 51)
- Area Under the Drug Concentration-Time Curve (AUC)(Predose up to Week 51)
- Concentration at End of Infusion (Cat EOI)(Week 24)
- Change From Baseline in AP-101 Levels in the Cerebrospinal Fluid (CSF) up to Week 24(Baseline, up to Week 24)
- Change From Baseline in Neurofilament Light Chain and Phospho-Neurofilament Heavy Chain Levels in the Cerebrospinal Fluid (CSF) up to Week 51(Baseline, up to Week 51)
研究者
研究点 (13)
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相关资讯
AL-S Pharma's AP-101 Shows Clinically Meaningful Disease Modification and Prolonged Survival in ALS Phase 2 Trial- AL-S Pharma's Phase 2 trial of AP-101, a human-derived antibody targeting misfolded SOD1, met its primary safety endpoint and demonstrated clinically meaningful disease modification in ALS patients.
- The treatment showed prolonged survival and delayed ventilatory support with significant effects in both sporadic ALS (p = 0.013) and SOD1 mutation carrier cohorts (p = 0.036).
- Biomarker analysis revealed reductions in key neuroaxonal injury markers including serum neurofilament light chain and cerebrospinal fluid phosphorylated neurofilament heavy chain after six months of treatment.
- The company is preparing for a confirmatory Phase 3 clinical trial aimed to initiate by the end of 2026, with AP-101 having received Orphan Drug designations from major regulatory agencies.6 months agoAL-S Pharma Reports Positive Phase 2 Results for AP-101 in ALS Treatment- AL-S Pharma announced positive topline results from its Phase 2 study of AP-101, a first-in-class monoclonal antibody targeting misfolded SOD1 protein in amyotrophic lateral sclerosis patients.
- The multicenter, randomized, double-blind, placebo-controlled study met its primary safety and tolerability endpoint in both sporadic ALS (N=52) and mutant SOD1-ALS (N=21) patients over 12 months of treatment.
- Clinically meaningful changes in exploratory outcome measures related to survival and non-invasive ventilation were observed, along with stabilization of clinical disease-staging and neurofilament biomarkers.
- This represents the first Phase 2 study to assess a SOD1-targeted therapeutic in both sporadic ALS and genetically determined SOD1-ALS patients, supporting the hypothesis that misfolded SOD1 protein plays a broader role in ALS pathogenesis.last year