A Two-Part Phase 3b Randomized, Double-Blind, Placebo-Controlled, Followed by Open-Label Extension, Multicenter Study of the Efficacy and Safety of MSC-NTF (NurOwn) in Participants With With Early Symptomatic and Moderate Disease Presentation in Amyotrophic Lateral Sclerosis (ALS)
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 200
- 试验地点
- 14
- 主要终点
- Change in the ALSFRS-R total score from baseline to Week 24
研究概览
简要总结
The goal of this two-part clinical trial is:
- to evaluate the safety and efficacy of Debamestrocel - MSC-NTF (NurOwn) compared to placebo in participants with early symptomatic ALS and moderate disease presentation in ALS; followed by 2) further evaluation by providing NurOwn to all participants in an open label extension period.
Researchers will compare NurOwn to a placebo (a look-alike substance that contains no drug) to evaluate the efficacy of NurOwn compared to placebo in the treatment of participants with ALS.
Participants will:
Receive NurOwn or a placebo every 8 weeks for 24 weeks. After that, every participant will receive NurOwn every 8 weeks for an additional 24 weeks.
They will visit the clinic approximately every 8 weeks for checkups and tests.
详细描述
This is a multicenter, Phase 3b study to assess the efficacy and safety of NurOwn in participants with early symptomatic ALS and moderate disease presentation in ALS. The study comprises two parts: a 24-week randomized, double blind placebo controlled period (Part A) followed by a 24-week open label expansion period (Part B).
Up to approximately 200 participants are planned to be enrolled and randomized 1:1 to the NurOwn and placebo groups in Part A. All eligible participants who complete Part A will have the option of entering Part B.
The trial includes a 9-week screening period. After the first screening visit (Screening Visit 1), there will be a Screening Visit 2, during which randomization 1:1 to the NurOwn and placebo groups will occur after confirming that all entry criteria are met. Following randomization, bone marrow aspiration will be scheduled. Stem cells from the bone marrow of all participants will be isolated, and then cryopreserved. Prior to each intrathecal (IT) dose administration, cells will be thawed, propagated, and induced into MSC-NTF cells (NurOwn).
In Part A, participants will receive NurOwn or placebo via IT injection every eight weeks at Weeks 0, 8, and 16.
In Part B, participants will receive NurOwn via IT injection every eight weeks at Weeks 24, 32, and 40.
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
Sponsor, CRO, vendors
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female participants 18 to 75 years old (inclusive) at Screening Visit
- •ALS diagnosed as laboratory-supported probable, clinically probable, or definite as defined by the revised El Escorial criteria.
- •Having onset of ALS symptoms, including muscle weakness, within 24 months from Screening Visit
- •≥2 points on each item of the ALSFRS-R at the Screening Visit
- •≤45 points on ALSFRS-R total score at Screening Visit
- •Upright slow vital capacity (SVC) measure ≥65% of predicted for gender, height, and age at Screening Visit
- •Participants must adhere to highly effective methods of contraception as specified in the study protocol.
排除标准
- •Prior stem cell therapy of any kind.
- •Active participation in any other ALS interventional study.
- •Inability to lie flat for the duration of IT cell treatment and/or bone marrow biopsy, or inability to tolerate study procedures for any other reason.
- •Any unstable clinically significant medical condition other than ALS
- •Any history of malignancy, within the previous 5 years, with the exception of localized skin cancers, cervical cancer in-situ or prostate cancer in-situ (with no evidence of metastasis, significant invasion, or reoccurrence within 3 years of baseline).
- •Primary brain cancer or cancer with CNS involvement is exclusionary.
- •Other types of motor neuron disease such as primary lateral sclerosis, progressive muscular atrophy, and progressive bulbar palsy.
- •Usage of a feeding tube at Screening Visit 1 or Screening Visit
- •Pregnant women or women currently breastfeeding.
研究组 & 干预措施
Debamestrocel - MSC-NTF (NurOwn)
NTF-secreting mesenchymal stem cells (MSC-NTF cells) are a novel cell-therapeutic approach aimed at effectively delivering NTFs directly to the site of damage in ALS patients
干预措施: Debamestrocel - MSC-NTF (NurOwn) (Biological)
Placebo
Placebo is comprised of Dulbecco Modified Eagle Medium (DMEM)
干预措施: Placebo (Biological)
结局指标
主要结局
Change in the ALSFRS-R total score from baseline to Week 24
时间窗: From baseline to Week 24
To evaluate the efficacy of NurOwn compared to placebo in the treatment of participants with ALS based on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) which is a 12-item clinician-administered questionnaire. Each item is scored between 0 and 4, with the total ALSFRS-R score between 0 and 48 where a higher score reflects a better outcome.
Frequency and severity of adverse events including treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), death, abnormalities in laboratory evaluations, physical examinations, vital signs and electrocardiogram (ECG) assessments
时间窗: From baseline to Week 48
To evaluate the safety and tolerability of NurOwn in the treatment of participants with ALS throughout the study including the DBPC period (Part A) to Week 24 and the Open Label Extension (Part B).
次要结局
- Change in SVC (%predicted) from baseline to Week 24(From baseline to Week 24)
- Change in HHD from baseline to Week 24(From baseline to Week 24)