A Study to Evaluate Transplantation of Astrocytes Derived From Human Embryonic Stem Cells, in Patients With Amyotrophic Lateral Sclerosis (ALS)

Study Overview
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Brief Summary
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This is a study of transplantation of Astrocytes derived from human embryonic stem cells, in patients with Amyotrophic Lateral Sclerosis (ALS). There will be no change in the routine ALS treatment of the patients enrolled into the study. Treatment will be administered in addition to the appropriate standard of care treatment. The study hypothesis is that transplantation of Astrocyte(AstroRx) cells can compensate for the malfunctioning of patients' own astrocytes by restoring physiological capabilities like the reuptake of excessive glutamate, reducing oxidative stress, reducing other toxic compounds, as well as by secreting different neuroprotective factors

Official Title
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A Phase I/IIa, Open Label, Dose-escalating Clinical Study to Evaluate the Safety, Tolerability and Theraputic Effects of Transplantation of Astrocytes Derived From Human Embryonic Stem Cells (hESC), in Patients With Amyotrophic Lateral Sclerosis (ALS)

Conditions
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ALS (Amyotrophic Lateral Sclerosis)

Intervention / Treatment
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* Biological: AstroRx


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: El Escorial criteria for probable or definite ALS Males and and non pregnant females between 18 and 70 years of age Patients with an ALS-FRS-R score of at least 30 with an ALS diagnosis of two years or less No history of active psychiatric disorder. Patients receiving antidepressants as a preventive treatment, with no history of active psychiatric disorder may be included. Patient has a good understanding of the study and nature of the procedure Patient provides written informed consent prior to any study procedure Patients should either be on a stable dose of Riluzole and/or Radicava® (if applicable) for at least 30 days, or not be treated with Riluzole and/or Radicava® Patient is medically able to tolerate immunosuppression regimen Presence of a willing and able caregiver who understands the need to attend all follow-up visits, even if mobility declines Main Exclusion Criteria: Patient has a past infection or a positive test for HBV,HCV or HIV Patient is in need of respiratory support Patient has a lower than 10/12 in ALS-FRS-R respiratory parameters or below 70% of predicted slow vital capacity (SVC) Patient has renal failure Patient has impaired hepatic function Patient has a Body Mass Index (BMI) of <18.5 or > 30 Patient suffers from significant cardiac disease, diabetes, autoimmune diseases, chronic severe infection, malignant disease or any other disease or condition that may risk the patient or interfere with the ability to interpret the study results Patient has systemic inflammation or active infections Patient has been treated previously with any stem cell therapy Current use of immunosuppressant medication or use of such medication within 6 weeks of Screening visit (Visit 0) Patient has participated in another clinical treatment trial or received other experimental medications outside of a clinical trial within 1 month prior to start of this study Any known immunodeficiency syndrome Any concomitant disease or condition limiting patient safety to participate

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Intervention Model: Sequential Assignment
Interventional Model Description: Dose-escalating, four subject-groups clinical study; a single treatment administration of AstroRx, administered in an escalating low, medium and high dose or two consecutive administrations of the medium dose separated by an interval. AstroRx will be administered by intrathecal (spinal) injection to subjects with ALS at the early disease stage.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AstroRx<br> | Biological: AstroRx<br>* Astrocytes derived from human embryonic stem cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment emergent adverse events as assessed by CTCAE Version 4.03 | Safety and tolerability assessment will be based on treatment emerged adverse events | 11 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the ALS functional rating scale | Preliminary efficacy assessment to measure response to treatment or progression of disease. Scale includes 12 questions related to tasks. Each task rated on a five-point scale from 0 = unable to do the task, to 4 = normal ability. Individual item scores are summed to produce a reported score of between 0 = worst and 48 = best. | 11 Months | 
| Change in predicted slow vital capacity (%SVC) | Preliminary efficacy assessment to measure respiratory muscle strength | 11 Months | 
| Change in muscle strength grading by JAMAR grip strength | Preliminary efficacy assessment to measure hand grip strength | 11 Months | 
| Change in muscle strength grading by hand held dynamometer (HHD) | Preliminary efficacy assessment to measure muscle strength in limb muscles | 11 Months | 
| Change in Quality of Life questionnaire (ALSAQ-40) | Preliminary efficacy assessment to measure the subjective well-being of patients | 11 Months |