The Evaluation of the Effect of Mesenchymal Stem Cells on the Immune System of Patients With ALS

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety of intrathecal administration of Wharton's Jelly Mesenchymal Stem Cells (WJMSC) and the impact on the immune system of patients with Amyotrophic Lateral Sclerosis.

Detailed Description
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Clinical Phase: I/II Population: Patients with Amyotrophic Lateral Sclerosis. Project Design: One arm, non-blinded, open label study Planned Sample Size: 20 patients Investigational Medicinal Product: active IMP - mesenchymal stem cells isolated from Wharton's jelly Screening: Three visits on site to check the eligibility criteria (around 90, 60 and 30 days before first IMP administration) Treatment (IMP administration): Each patient will receive IMP three times: on baseline (day 0), 30 and 60 days after baseline (+/- 7 days). Administration route: intrathecal Follow up: Duration: 18 months after first IMP administration Four on-site visits (3, 6, 9, 12 months after first IMP administration) and seven phone visits (4, 5, 7, 8, 10, 11 and 18 months after first IMP administration)

Official Title
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The Evaluation of the Effect of Wharton's Jelly Mesenchymal Stem Cells (WJMSCs) on the Immune System of Patients With Amyotrophic Lateral Sclerosis (ALS)

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: Mesenchymal stem cells isolated from Wharton's jelly


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (at least 18 years old) The minimum patient's weight is not less than 40 kg Diagnosis of sporadic ALS, definite or probable, as defined by El Escorial World Federation of Neurology criteria History of ALS symptoms less than 2 years duration from the first symptoms of the disease More than 6 months from diagnosis of the disease Disease progression at 6 past months at least 3 points during this period of time assessed in ALSFRS-R scale ALSFRS-R scale of at least 30 at screening appointment Forced vital capacity >70% of predicted value for age, gender and height Treatment with stable dose of riluzole(2x 50mg per 24h) before baseline visit (for at least 1 month) Capable of providing written informed consent Able to comply with study requirements and willing to follow all study procedures and follow-up visits Women of child-bearing age and men with partners of child-bearing potential must agree to use two forms of contraceptive therapy throughout the course of the trial Women of child-bearing age must undergo pregnancy test Polish-language native speakers or patients who are proficient in the Polish language Exclusion Criteria: Pregnancy or breastfeeding Tracheostomy Ventilator dependence Renal disease with creatinine >2mg/dl Liver disease with ALT, AST or GGTP 2-fold higher than upper normal limit Positive test for HBV, HCV, HIV with NAT method Positive tests for syphilis Any other clinically significant abnormalities on laboratory evaluation Any condition that would compromise ability of undergoing lumbar puncture Active systemic disease Autoimmune disease (Hashimoto disease under control is allowed) Uncontrolled diabetes (HbA1c > 8%) Pulmonary disease that could affect interpretation of spirometry Neurological concomitant disease Unstable psychiatric concomitant disease High risk of suicide History of substance abuse within past year History of malignancy, within the previous 5 years, including melanoma with exception of localized skin cancers Any other clinically significant medical condition that can compromise patient's safety in the opinion of the investigator Treatment with immunomodulatory drugs (for example immunoglobulins, corticosteroids or other immunosuppressant) in last 6 months Participation in another clinical trial in last 6 months Previous cellular therapy of any kind Hypersensitivity to any component used in the cell culture Nuchal rigidity and other signs of meningitis Patients on chronic anticoagulation treatment (heparin/ warfarin/acenocoumarol/(N)OAC)

Ages Eligible for Study
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Minimum Age: 18 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment arm<br>It is planned that IMP administration will be performed three times for each enrolled patient. IMP administration could be performed only if the patients does not have any contraindications for lumbar puncture. | Drug: Mesenchymal stem cells isolated from Wharton's jelly<br>* Intrathecal administration of mesenchymal stem cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The number of (S)AESI [(Serious) Adverse Event of Special Interest] | (S)AESI are defined as: Meningitis and encephalitis. Toxic encephalopathy. High fever >39⁰C. Epileptic seizures that are not connected to conditions above (meningitis, encephalitis, toxic encephalopathy, high fever). | 3 month FU (follow-up) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease progression | Disease progression assessed in ALSFRS-R scale (Revised Amyotrophic Lateral Sclerosis Functional Rating Scale). Higher scores mean a better outcome. Minimum: 0 points Maximum: 48 points | screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 18 month FU | 
| Pulmonary function decline | Pulmonary function decline assessed in spirometry (forced vital capacity) | screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU. | 
| Muscle strength decline | Muscle strength decline | screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU | 
| Upper motor neuron function | Upper motor neuron function assessed in UMNS scale (Upper Motor Neuron Scale). Best outcome 16 points, worst outcomes: 0 points and 48 points Minimum: 0 points Maximum: 48 points | screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU | 
| Cognitive function | Cognitive function assessed in ECAS (The Edinburgh Cognitive and Behavioural ALS Screen). Higher scores mean a better outcome. Minimum: 0 points Maximum: 136 points | screening and 12 month FU | 
| Quality of life changes | Quality of life changes, assessed by EQ-5D questionnaire - standardized instrument for measuring generic health status. Higher scores mean a better outcome. | screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 18 month FU | 
| The change of defined cytokines, chemokines, growth factors and pNFH (phosphorylated neurofilament heavy chain) level in CSF (Cerebrospinal fluid) | The change of defined cytokines, chemokines, growth factors and pNFH level assessed in the samples of CSF | run-in visit (-60 day), at baseline and at 1, 2 and 6 month FU (12 month FU optional) | 
| The change of defined cytokines, chemokines level in blood | The change of defined cytokines, chemokines level assessed in the samples of blood serum | screening visit, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU. | 
| The change of creatinine and p75ECD level in urine | The change of creatinine and p75ECD level | screening visit, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU. | 
| Muscle function changes | Muscle function changes, assessed based on EMG examination (Electrophysiological examination of the muscle - MUNIX - motor unit number estimation) | baseline and at 1, 2, 6 and 12 month FU | 
| The change of the brain visualization | The change of the brain visualization in MRI (T1, T2 and DTI) | run-in visit (-60 day), 6 and 12 month FU | 
| SAE (Serious Adverse Event)/AE (Adverse Event) and (S)AESI | The number of SAE/AE and (S)AESI - defined as in Outcome 1 | 18 month FU | 
| Survival period to disease progression | The number of days from patients randomization to the end of the patients participation in the trial or to the one of the following: PAV (permanent assisted ventilation) Tracheostomy Death | 18 month FU | 
| Mortality rate | Percentage of deaths in the entire study population. | 18 month FU | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyotrophic Lateral Sclerosis, Stem Cells