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

Amyotrophic Lateral Sclerosis Clinical Trial

— ALSTEM  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04651855
• Other study ID #: ALSTEM
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: December 2, 2020
• Est. completion date: April 2023

Study information

• Verified date: April 2022
• Source: Polski Bank Komorek Macierzystych JSC (PBKM)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 20
• Est. completion date: April 2023
• Est. primary completion date: March 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• Mesenchymal stem cells isolated from Wharton's jelly
Intrathecal administration of mesenchymal stem cells

Locations

Country	Name	City	State
Poland	JST sp. z o.o.	Czestochowa

Sponsors (2)

Lead Sponsor	Collaborator
Polski Bank Komorek Macierzystych JSC (PBKM)	National Center for Research and Development, Poland

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of (S)AESI [(Serious) Adverse Event of Special Interest]	(S)AESI are defined as: Meningitis and encephalitis.; Toxic encephalopathy.; High fever >39°C.; Epileptic seizures that are not connected to conditions above (meningitis, encephalitis, toxic encephalopathy, high fever).	3 month FU (follow-up)
Secondary	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
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Mortality rate	Percentage of deaths in the entire study population.	18 month FU