Clinical trial NCT04651855: The Evaluation of the Effect of Mesenchymal Stem Cells on the Immune System of Patients With ALS
Official title: The Evaluation of the Effect of Wharton's Jelly Mesenchymal Stem Cells (WJMSCs) on the Immune System of Patients With Amyotrophic Lateral Sclerosis (ALS)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: Amyotrophic Lateral Sclerosis
Stem Cells
Lead sponsor: Polski Bank Komorek Macierzystych JSC (PBKM)
Sponsor class: INDUSTRY
Collaborators: name: National Center for Research and Development, Poland
First posted: 2020-12-03
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)

Eligibility criteria: 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)

Primary outcomes:
measure: The number of (S)AESI [(Serious) Adverse Event of Special Interest]
timeFrame: 3 month FU (follow-up)
Secondary outcomes:
measure: Disease progression
timeFrame: 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
measure: Pulmonary function decline
timeFrame: screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU.
measure: Muscle strength decline
timeFrame: screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU
measure: Upper motor neuron function
timeFrame: screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU
measure: Cognitive function
timeFrame: screening and 12 month FU
measure: Quality of life changes
timeFrame: 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
measure: The change of defined cytokines, chemokines, growth factors and pNFH (phosphorylated neurofilament heavy chain) level in CSF (Cerebrospinal fluid)
timeFrame: run-in visit (-60 day), at baseline and at 1, 2 and 6 month FU (12 month FU optional)
measure: The change of defined cytokines, chemokines level in blood
timeFrame: screening visit, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU.
measure: The change of creatinine and p75ECD level in urine
timeFrame: screening visit, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU.
measure: Muscle function changes
timeFrame: baseline and at 1, 2, 6 and 12 month FU
measure: The change of the brain visualization
timeFrame: run-in visit (-60 day), 6 and 12 month FU
measure: SAE (Serious Adverse Event)/AE (Adverse Event) and (S)AESI
timeFrame: 18 month FU
measure: Survival period to disease progression
timeFrame: 18 month FU
measure: Mortality rate
timeFrame: 18 month FU
Other outcomes:
Locations:
city: Częstochowa
country: Poland
facility: JST sp. z o.o.
Study officials:
References: