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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Drug: Mesenchymal stem cells isolated from Wharton's jelly

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 Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Poland
  • Częstochowa, Poland, 42-202
    • JST sp. z o.o.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment arm; 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; Intrathecal administration of mesenchymal stem cells

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Polski Bank Komorek Macierzystych JSC (PBKM)
• Collaborators: National Center for Research and Development, Poland

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 2, 2020
• Primary Completion (ACTUAL): March 8, 2022
• Study Completion (ANTICIPATED): April 1, 2023

Study Registration Dates

• First Submitted: September 30, 2020
• First Submitted That Met QC Criteria: December 2, 2020
• First Posted (ACTUAL): December 3, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 3, 2022
• Last Update Submitted That Met QC Criteria: April 27, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Amyotrophic Lateral Sclerosis; Stem Cells
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: ALSTEM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No