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

Primary Purpose

Amyotrophic Lateral Sclerosis

Status

Active

Phase

Phase 1

Locations

Poland

Study Type

Interventional

Intervention

Mesenchymal stem cells isolated from Wharton's jelly

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring Amyotrophic Lateral Sclerosis, Stem Cells

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Adult patients (at least 18 years old)
The minimum patient's weight is not less than 40 kg
Diagnosis of sporadic ALS, definite or probable, as defined by El Escorial World Federation of Neurology criteria
History of ALS symptoms less than 2 years duration from the first symptoms of the disease
More than 6 months from diagnosis of the disease
Disease progression at 6 past months at least 3 points during this period of time assessed in ALSFRS-R scale
ALSFRS-R scale of at least 30 at screening appointment
Forced vital capacity >70% of predicted value for age, gender and height
Treatment with stable dose of riluzole(2x 50mg per 24h) before baseline visit (for at least 1 month)
Capable of providing written informed consent
Able to comply with study requirements and willing to follow all study procedures and follow-up visits
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
Women of child-bearing age must undergo pregnancy test
Polish-language native speakers or patients who are proficient in the Polish language

Exclusion Criteria:

Pregnancy or breastfeeding
Tracheostomy
Ventilator dependence
Renal disease with creatinine >2mg/dl
Liver disease with ALT, AST or GGTP 2-fold higher than upper normal limit
Positive test for HBV, HCV, HIV with NAT method
Positive tests for syphilis
Any other clinically significant abnormalities on laboratory evaluation
Any condition that would compromise ability of undergoing lumbar puncture
Active systemic disease
Autoimmune disease (Hashimoto disease under control is allowed)
Uncontrolled diabetes (HbA1c > 8%)
Pulmonary disease that could affect interpretation of spirometry
Neurological concomitant disease
Unstable psychiatric concomitant disease
High risk of suicide
History of substance abuse within past year
History of malignancy, within the previous 5 years, including melanoma with exception of localized skin cancers
Any other clinically significant medical condition that can compromise patient's safety in the opinion of the investigator
Treatment with immunomodulatory drugs (for example immunoglobulins, corticosteroids or other immunosuppressant) in last 6 months
Participation in another clinical trial in last 6 months
Previous cellular therapy of any kind
Hypersensitivity to any component used in the cell culture
Nuchal rigidity and other signs of meningitis
Patients on chronic anticoagulation treatment (heparin/ warfarin/acenocoumarol/(N)OAC)

Sites / Locations

JST sp. z o.o.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment arm

Arm Description

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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

Pulmonary function decline

Pulmonary function decline assessed in spirometry (forced vital capacity)

Muscle strength decline

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

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

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.

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

The change of defined cytokines, chemokines level in blood

The change of defined cytokines, chemokines level assessed in the samples of blood serum

The change of creatinine and p75ECD level in urine

The change of creatinine and p75ECD level

Muscle function changes

Muscle function changes, assessed based on EMG examination (Electrophysiological examination of the muscle - MUNIX - motor unit number estimation)

The change of the brain visualization

The change of the brain visualization in MRI (T1, T2 and DTI)

SAE (Serious Adverse Event)/AE (Adverse Event) and (S)AESI

The number of SAE/AE and (S)AESI - defined as in Outcome 1

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

Mortality rate

Percentage of deaths in the entire study population.

Full Information

NCT ID

NCT04651855

First Posted

September 30, 2020

Last Updated

April 27, 2022

Sponsor

Polski Bank Komorek Macierzystych JSC (PBKM)

Collaborators

National Center for Research and Development, Poland

1. Study Identification

Unique Protocol Identification Number

NCT04651855

Brief Title

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

Acronym

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)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

December 2, 2020 (Actual)

Primary Completion Date

March 8, 2022 (Actual)

Study Completion Date

April 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Polski Bank Komorek Macierzystych JSC (PBKM)

Collaborators

National Center for Research and Development, Poland

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic Lateral Sclerosis, Stem Cells

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment arm

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Mesenchymal stem cells isolated from Wharton's jelly

Intervention Description

Intrathecal administration of mesenchymal stem cells

Primary Outcome Measure Information:

Title

The number of (S)AESI [(Serious) Adverse Event of Special Interest]

Description

Time Frame

3 month FU (follow-up)

Secondary Outcome Measure Information:

Title

Disease progression

Description

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

Time Frame

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

Title

Pulmonary function decline

Description

Pulmonary function decline assessed in spirometry (forced vital capacity)

Time Frame

screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU.

Title

Muscle strength decline

Description

Muscle strength decline

Time Frame

screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU

Title

Upper motor neuron function

Description

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

Time Frame

screening, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU

Title

Cognitive function

Description

Cognitive function assessed in ECAS (The Edinburgh Cognitive and Behavioural ALS Screen). Higher scores mean a better outcome. Minimum: 0 points Maximum: 136 points

Time Frame

screening and 12 month FU

Title

Quality of life changes

Description

Quality of life changes, assessed by EQ-5D questionnaire - standardized instrument for measuring generic health status. Higher scores mean a better outcome.

Time Frame

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

Title

The change of defined cytokines, chemokines, growth factors and pNFH (phosphorylated neurofilament heavy chain) level in CSF (Cerebrospinal fluid)

Description

The change of defined cytokines, chemokines, growth factors and pNFH level assessed in the samples of CSF

Time Frame

run-in visit (-60 day), at baseline and at 1, 2 and 6 month FU (12 month FU optional)

Title

The change of defined cytokines, chemokines level in blood

Description

The change of defined cytokines, chemokines level assessed in the samples of blood serum

Time Frame

screening visit, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU.

Title

The change of creatinine and p75ECD level in urine

Description

The change of creatinine and p75ECD level

Time Frame

screening visit, run-in period (-60 day and -30 day), at baseline and at 1, 2, 3, 6, 9 and 12 month FU.

Title

Muscle function changes

Description

Muscle function changes, assessed based on EMG examination (Electrophysiological examination of the muscle - MUNIX - motor unit number estimation)

Time Frame

baseline and at 1, 2, 6 and 12 month FU

Title

The change of the brain visualization

Description

The change of the brain visualization in MRI (T1, T2 and DTI)

Time Frame

run-in visit (-60 day), 6 and 12 month FU

Title

SAE (Serious Adverse Event)/AE (Adverse Event) and (S)AESI

Description

The number of SAE/AE and (S)AESI - defined as in Outcome 1

Time Frame

18 month FU

Title

Survival period to disease progression

Description

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

Time Frame

18 month FU

Title

Mortality rate

Description

Percentage of deaths in the entire study population.

Time Frame

18 month FU

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adult patients (at least 18 years old) The minimum patient's weight is not less than 40 kg Diagnosis of sporadic ALS, definite or probable, as defined by El Escorial World Federation of Neurology criteria History of ALS symptoms less than 2 years duration from the first symptoms of the disease More than 6 months from diagnosis of the disease Disease progression at 6 past months at least 3 points during this period of time assessed in ALSFRS-R scale ALSFRS-R scale of at least 30 at screening appointment Forced vital capacity >70% of predicted value for age, gender and height Treatment with stable dose of riluzole(2x 50mg per 24h) before baseline visit (for at least 1 month) Capable of providing written informed consent Able to comply with study requirements and willing to follow all study procedures and follow-up visits 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 Women of child-bearing age must undergo pregnancy test Polish-language native speakers or patients who are proficient in the Polish language Exclusion Criteria: Pregnancy or breastfeeding Tracheostomy Ventilator dependence Renal disease with creatinine >2mg/dl Liver disease with ALT, AST or GGTP 2-fold higher than upper normal limit Positive test for HBV, HCV, HIV with NAT method Positive tests for syphilis Any other clinically significant abnormalities on laboratory evaluation Any condition that would compromise ability of undergoing lumbar puncture Active systemic disease Autoimmune disease (Hashimoto disease under control is allowed) Uncontrolled diabetes (HbA1c > 8%) Pulmonary disease that could affect interpretation of spirometry Neurological concomitant disease Unstable psychiatric concomitant disease High risk of suicide History of substance abuse within past year History of malignancy, within the previous 5 years, including melanoma with exception of localized skin cancers Any other clinically significant medical condition that can compromise patient's safety in the opinion of the investigator Treatment with immunomodulatory drugs (for example immunoglobulins, corticosteroids or other immunosuppressant) in last 6 months Participation in another clinical trial in last 6 months Previous cellular therapy of any kind Hypersensitivity to any component used in the cell culture Nuchal rigidity and other signs of meningitis Patients on chronic anticoagulation treatment (heparin/ warfarin/acenocoumarol/(N)OAC)

Facility Information:

Facility Name

JST sp. z o.o.

City

Częstochowa

ZIP/Postal Code

42-202

Country

Poland

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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