Safety and Efficacy of Repeated Administrations of NurOwn® in ALS Patients

Study Overview
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Brief Summary
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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

Detailed Description
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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

Official Title
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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

Conditions
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Amyotrophic Lateral Sclerosis (ALS)

Intervention / Treatment
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* Biological: NurOwn® (MSC-NTF cells)
* Other: Placebo
* Other: Bone Marrow aspiration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Double-Blind, Placebo-Controlled Multicenter Study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: NurOwn® (MSC-NTF cells)<br>Three Intrathecal administrations of NurOwn® (MSC-NTF cells) at bi-monthly intervals | Biological: NurOwn® (MSC-NTF cells)<br>* Autologous transplantation of bone marrow derived mesenchymal stem cells propagated ex vivo and induced to secrete neurotrophic factors<br>Other: Bone Marrow aspiration<br>* Bone Marrow aspiration<br>|
| Placebo Comparator: Placebo<br>Three Intrathecal administrations of Placebo at bi-monthly intervals | Other: Placebo<br>* Placebo<br>Other: Bone Marrow aspiration<br>* Bone Marrow aspiration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the efficacy and safety of NurOwn® (autologous MSC-NTF cells) as compared to placebo as measured by the amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) | To determine efficacy and safety of repeat intrathecal injections of NurOwn® as compared to Placebo given three times two months apart to participants with Amyotrophic Lateral Sclerosis | 28 weeks following the first treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers | To evaluate biomarkers (such as cell-secreted neurothrophic factors, inflammatory factors, and cytokines in pg/ml) in the cerebrospinal fluid (CSF) as well as in serum samples throughout the study to evaluate their relationship to treatment with NurOwn® (MSC-NTF cells) | Through selected post-treatment time points up to 20 weeks post transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autologous, MSC, Neurotrophic factors