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

Phase 1

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Drug: Mesenchymal stem cells isolated from Wharton's jelly

• Registration Number: NCT04651855
• Lead Sponsor: Polski Bank Komorek Macierzystych JSC (PBKM)

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)

Study Timeline

• Study First Submitted: 2020-09-30
• Study Start: 2020-12-02
• Study First Submitted QC: 2020-12-02
• Study First Posted: 2020-12-03
• Primary Completion: 2022-03-08
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-27
• Last Update Posted: 2022-05-03
• Study Completion: 2023-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment arm	Mesenchymal stem cells isolated from Wharton's jelly	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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)
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
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.
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)
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
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
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
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
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
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)
Mortality rate	18 month FU	Percentage of deaths in the entire study population.

Trial Locations

Locations (1)

JST sp. z o.o.; 🇵🇱 Częstochowa, Poland