A Phase 3, Randomized Double-Blind, Placebo-Controlled Multicenter Study to Evaluate Efficacy and Safety of Repeated Administration of NurOwn® (Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors) in Participants With ALS
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 196
- 试验地点
- 12
- 主要终点
- The Proportion of NurOwn® Treated Participants With a ≥1.25 Points/Month Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score at 28 Weeks Following the First Treatment as Compared to Placebo
研究概览
简要总结
This study will evaluate the safety and efficacy of repeated administration of NurOwn® (MSC-NTF cells) therapy, which is based on transplantation of autologous bone marrow derived mesenchymal stromal cells (MSC), which are enriched from the patient's own bone marrow, propagated ex vivo and induced to secrete Neurotrophic factors (NTFs).
The autologous NurOwn® (MSC-NTF cells) are back-transplanted into the patient intrathecally by standard lumbar puncture where neurons and glial cells are expected to take up the neurotrophic factors secreted by the transplanted cells
详细描述
Neurotrophic factors (NTFs) are potent survival factors for embryonic, neonatal, and adult neurons and are considered potential therapeutic candidates for ALS. Delivery of multiple NTFs to the immediate environment of afflicted neurons in ALS patients is expected to improve their survival and thus slow down disease progression and alleviate symptoms. NTF-secreting mesenchymal stromal cells (MSC-NTF cells) are a novel cell-therapeutic approach aimed at effectively delivering NTFs directly to the site of damage in ALS patients.
Participants meeting the inclusion and exclusion criteria will be randomized and will undergo bone-marrow aspiration. MSC of the participants randomized to the treatment group will be induced into MSC-NTF cells. Participants will undergo a total of three intrathecal (IT) transplantations with NurOwn® (MSC-NTF cells) or matching placebo at three bi-monthly intervals
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)
盲法说明
This is a double-blind study where the investigators, participants and all sponsor and CRO personnel involved in the conduct, data management or analysis of the study will remain blinded to the treatment assignments
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •ALS diagnosed as possible, laboratory-supported probable, probable, or definite as defined by revised El Escorial criteria.
- •Having onset of ALS disease symptoms, including limb weakness within 24 months at the Screening Visit.
- •ALSFRS-R ≥ 25 at the screening Visit.
- •Upright slow vital capacity (SVC) measure ≥ 65% of predicted for gender, height, and age at the screening Visit.
- •Rapid progressors
- •Participants taking a stable dose of Riluzole are permitted in the study
- •Citizen or permanent resident of the United States or Canadian citizen able to travel to a US site for all follow-up study visits
排除标准
- •Prior stem cell therapy of any kind
- •History of autoimmune or other serious disease (including malignancy and immune deficiency) that may confound study results
- •Current use of immunosuppressant medication or anticoagulants (per Investigator discretion)
- •Exposure to any other experimental agent or participation in an ALS clinical trial within 30 days prior to Screening Visit
- •Use of RADICAVA (edaravone injection) within 30 days of screening or intent to use edaravone at any time during the course of the study including the follow up period
- •Use of non-invasive ventilation (BIPAP), diaphragm pacing system or invasive ventilation (tracheostomy)
- •Feeding tube
- •Pregnant women or women currently breastfeeding
结局指标
主要结局
The Proportion of NurOwn® Treated Participants With a ≥1.25 Points/Month Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score at 28 Weeks Following the First Treatment as Compared to Placebo
时间窗: 28 weeks following the first intrathecal injection
The ALSFRS-R is a quickly administered (10 minutes) ordinal, validated rating scale (ratings 0-4) used to determine participants' assessment of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS. Initial validity was established by documenting that in ALS patients, change in ALSFRS-R scores correlated with change in strength over time, as measured by quantitative neuromuscular strength testing, and with quality of life measures, and predicted survival. The total score of ALSFRS-R ranges from 0-48, with higher score being better.
次要结局
- NurOwn® (MSC-NTF Cells) Treated Patients vs. Placebo Treated Patients as Measured by the Combined Assessment of Function and Survival at 28 Weeks(28 weeks following the first intrathecal injection)
- Number of Participants Whose Disease Progression is Halted or Improved as Measured by a 100% or Greater Improvement in Post-treatment Slope vs. Pre-treatment Slope in ALSFRS-R Score of NurOwn® Treatment vs. Placebo(28 weeks following the first intrathecal injection)
- Score of NurOwn® (MSC-NTF Cells) Treated Patients vs. Placebo Treated Patients as Measured by Change From Baseline in ALSFRS-R Score at Week 28(28 weeks following the first intrathecal injection)