Autologous Multipotent Mesenchymal Stromal Cells in the Treatment of Amyotrophic Lateral Sclerosis (AMSC-ALS-001)

A Prospective, Non-randomized, Open Label Study to Assess the Safety and the Efficacy of Autologous Multipotent Mesenchymal Stromal Cells in the Treatment of Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that targets motor neurons. Prognosis is invariably fatal within 3-5 years since manifestation of the disease. Despite improved understanding of the mechanisms underlying ALS, the treatment remains essentially only supportive and focused on symptoms relief. Over the past few years, stem cell research has expanded greatly as a tool for developing new therapies to treat incurable diseases. Stem cell therapy has been shown as promising in several animal ALS models and human clinical trials.

Study Overview

• Status: Completed
• Conditions: Motor Neuron Disease, Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Biological: Suspension of human autologous MSC 3P in 1.5 ml

Detailed Description

Subjects will be assigned to autologous mesenchymal stromal cell (AMSC) treatment according to inclusion and exclusion criteria (see below) screened four times prior to administration. Then the subjects will be observed for three consecutive yearsAfter a half year of screening period, the autologous multipotent mesenchymal stromal cells from bone marrow will be isolated. The cells will be cultivated for 3 passages (3 - 4 weeks) in order to get sufficient amount for therapy, cell suspension for intrathecal application will be prepared and introduced intrathecally through lumbar puncture. Subsequently, all the subjects will be observed at the range of standard medical care used at these types of interventions.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. established diagnosis of definite ALS according to El Escorial criteria
2. riluzole naive or stable dose for at least 2 months,
3. life expectancy more than 2 years
4. patients able to provide written informed consent.

Exclusion Criteria:

1. FVC less than 70%
2. in case of primary bulbar paralysis less than 15 points on Norris bulbar scale,
3. less than 15 points on Norris spinal scale,
4. pregnancy, breastfeeding
5. coagulopathy,
6. skin infection at the site of bone marrow aspiration or application of the cell product,
7. gastrostomy,
8. any significant medical condition that would compromise the safety of the patient (e.g. recent myocardial infarction, congestive heart failure, renal failure, liver failure, cancer, systemic infection, recurrent thromboembolic disease .....),
9. alcohol or drug abuse
10. cancer.
11. women of childbearing potential not using effective contraception (established oral contraception, intrauterine device, ligation of the uterine tube) including proven contraceptive measures taken by their sexual partners
12. fertile men not using proven contraceptive measures including effective contraception of their partner (established oral contraception, intrauterine device, ligation of the uterine tube)

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: Autologous Multipotent MSC; Patients with intrathecal administration of Suspension of human autologous MSC 3P in 1.5 ml	Biological: Suspension of human autologous MSC 3P in 1.5 ml; Intrathecal application of Autologous Multipotent Mesenchymal Stromal Cells 3P suspension

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Complications related to the medicinal product application - new neurological deficit and occurrence of other adverse events	Complications at the site of intrathecal infusion of the medicinal product and no new neurological deficit (meningism, paraplegia, urinary incontinence) not attributed to the natural progression of the ALS disease will be recorded at Visits I, III, IV, V, VI, and IX. Occurrence of other potential adverse events, including headache, respiratory failure, leukocytosis, cervical spine stenosis, cystitis and hyperhydrosis will be evaluated on the severity scale (1=mild, 2=moderate, 3=severe). Brain and spinal cord MRI will be performed at Visits I and IX to exclude treatment-related tumor formation, pathological contrast enhancement or other structural pathology.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Inhibition of the disease progression - ALS functional rating scale	Inhibition of the disease progression will be recorded by ALS functional rating scale (ALSFRS) at Visits I, III, and VI through X. Measures (all 4-0): speech; salivation; swallowing; handwriting; cutting food and handling utensils (with or without gastrostomy); dressing and hygiene; turning in bed and adjusting bed clothes; walking; climbing stairs; breathing ALSFRS = SUM (points for all 10 measures) Interpretation: minimum score: 0 maximum score: 40 The higher the score the more function is retained.	18 months
Efficacy: Inhibition of the disease progression - Norris scale	Inhibition of the disease progression will be recorded by Norris scale at Visits I, III, and VI through X. Norris scal has has 22 items examining bulbar, respiratory, trunk, arm, leg, and general domains involving reflexes, fasciculation, and muscle atrophy. The scale also measures emotional lability, fatigability and leg rigidity. The Norris scale has a linear decline during the course of ALS.	18 months
Efficacy: Inhibition of the disease progression - Forced vital capacity (FVC)	FVC (%) will be measured at Visits I, and VI through X.	18 months

Collaborators and Investigators

• Sponsor: Bioinova, s.r.o.
• Collaborators: Department of Neurology, University Hospital Motol, Prague, Czech Republic

Publications and helpful links

General Publications

• Sykova E, Rychmach P, Drahoradova I, Konradova S, Ruzickova K, Vorisek I, Forostyak S, Homola A, Bojar M. Transplantation of Mesenchymal Stromal Cells in Patients With Amyotrophic Lateral Sclerosis: Results of Phase I/IIa Clinical Trial. Cell Transplant. 2017 Apr 13;26(4):647-658. doi: 10.3727/096368916X693716. Epub 2016 Nov 7.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2012
• Primary Completion (ACTUAL): August 18, 2017
• Study Completion (ACTUAL): August 18, 2017

Study Registration Dates

• First Submitted: July 20, 2017
• First Submitted That Met QC Criteria: February 1, 2019
• First Posted (ACTUAL): February 4, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2019
• Last Update Submitted That Met QC Criteria: February 11, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• 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: AMSC-ALS-001