Amyotrophic Lateral Sclerosis
Conditions
Keywords
Amyotrophic Lateral Sclerosis, Stem Cells
Brief summary
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
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)
Interventions
DRUGMesenchymal stem cells isolated from Wharton's jelly
Intrathecal administration of mesenchymal stem cells
Sponsors
National Center for Research and Development, Poland
Polski Bank Komorek Macierzystych JSC (PBKM)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult patients (at least 18 years old) 2. The minimum patient's weight is not less than 40 kg 3. Diagnosis of sporadic ALS, definite or probable, as defined by El Escorial World Federation of Neurology criteria 4. History of ALS symptoms less than 2 years duration from the first symptoms of the disease 5. More than 6 months from diagnosis of the disease 6. Disease progression at 6 past months at least 3 points during this period of time assessed in ALSFRS-R scale 7. ALSFRS-R scale of at least 30 at screening appointment 8. Forced vital capacity \>70% of predicted value for age, gender and height 9. Treatment with stable dose of riluzole(2x 50mg per 24h) before baseline visit (for at least 1 month) 10. Capable of providing written informed consent 11. Able to comply with study requirements and willing to follow all study procedures and follow-up visits 12. 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 13. Women of child-bearing age must undergo pregnancy test 14. Polish-language native speakers or patients who are proficient in the Polish language
Exclusion criteria
1. Pregnancy or breastfeeding 2. Tracheostomy 3. Ventilator dependence 4. Renal disease with creatinine \>2mg/dl 5. Liver disease with ALT, AST or GGTP 2-fold higher than upper normal limit 6. Positive test for HBV, HCV, HIV with NAT method 7. Positive tests for syphilis 8. Any other clinically significant abnormalities on laboratory evaluation 9. Any condition that would compromise ability of undergoing lumbar puncture 10. Active systemic disease 11. Autoimmune disease (Hashimoto disease under control is allowed) 12. Uncontrolled diabetes (HbA1c \> 8%) 13. Pulmonary disease that could affect interpretation of spirometry 14. Neurological concomitant disease 15. Unstable psychiatric concomitant disease 16. High risk of suicide 17. History of substance abuse within past year 18. History of malignancy, within the previous 5 years, including melanoma with exception of localized skin cancers 19. Any other clinically significant medical condition that can compromise patient's safety in the opinion of the investigator 20. Treatment with immunomodulatory drugs (for example immunoglobulins, corticosteroids or other immunosuppressant) in last 6 months 21. Participation in another clinical trial in last 6 months 22. Previous cellular therapy of any kind 23. Hypersensitivity to any component used in the cell culture 24. Nuchal rigidity and other signs of meningitis 25. Patients on chronic anticoagulation treatment (heparin/ warfarin/acenocoumarol/(N)OAC)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The number of (S)AESI [(Serious) Adverse Event of Special Interest] | 3 month FU (follow-up) | (S)AESI are defined as: 1. Meningitis and encephalitis. 2. Toxic encephalopathy. 3. High fever \>39⁰C. 4. Epileptic seizures that are not connected to conditions above (meningitis, encephalitis, toxic encephalopathy, high fever). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease progression | 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 | 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 |
| Pulmonary function decline | screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU. | Pulmonary function decline assessed in spirometry (forced vital capacity) |
| 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 | Muscle strength decline |
| Upper motor neuron function | 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 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 |
| Cognitive function | screening and 12 month FU | Cognitive function assessed in ECAS (The Edinburgh Cognitive and Behavioural ALS Screen). Higher scores mean a better outcome. Minimum: 0 points Maximum: 136 points |
| Quality of life changes | 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 | Quality of life changes, assessed by EQ-5D questionnaire - standardized instrument for measuring generic health status. Higher scores mean a better outcome. |
| The change of defined cytokines, chemokines level in blood | 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 defined cytokines, chemokines level assessed in the samples of blood serum |
| The change of creatinine and p75ECD level in urine | 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 |
| Muscle function changes | baseline and at 1, 2, 6 and 12 month FU | Muscle function changes, assessed based on EMG examination (Electrophysiological examination of the muscle - MUNIX - motor unit number estimation) |
| The change of the brain visualization | run-in visit (-60 day), 6 and 12 month FU | The change of the brain visualization in MRI (T1, T2 and DTI) |
| SAE (Serious Adverse Event)/AE (Adverse Event) and (S)AESI | 18 month FU | The number of SAE/AE and (S)AESI - defined as in Outcome 1 |
| Survival period to disease progression | 18 month FU | 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 |
| Mortality rate | 18 month FU | Percentage of deaths in the entire study population. |
| The change of defined cytokines, chemokines, growth factors and pNFH (phosphorylated neurofilament heavy chain) level in CSF (Cerebrospinal fluid) | 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, growth factors and pNFH level assessed in the samples of CSF |
Countries
Poland
Outcome results
None listed