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

• ClinicalTrials.gov Identifier: NCT03828123
• Recruitment Status: Completed
• First Posted: February 4, 2019
• Last Update Posted: February 12, 2019
• Sponsor: Bioinova, s.r.o.
• Collaborator: Department of Neurology, University Hospital Motol, Prague, Czech Republic
• Information provided by (Responsible Party): Bioinova, s.r.o.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Motor Neuron Disease, Amyotrophic Lateral Sclerosis	Biological: Suspension of human autologous MSC 3P in 1.5 ml	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: January 2012
• Actual Primary Completion Date: August 18, 2017
• Actual Study Completion Date: August 18, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Safety: Complications related to the medicinal product application - new neurological deficit and occurrence of other adverse events [ Time Frame: 1 year ]

   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.

Secondary Outcome Measures :

1. Efficacy: Inhibition of the disease progression - ALS functional rating scale [ Time Frame: 18 months ]

   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):

   1. speech
   2. salivation
   3. swallowing
   4. handwriting
   5. cutting food and handling utensils (with or without gastrostomy)
   6. dressing and hygiene
   7. turning in bed and adjusting bed clothes
   8. walking
   9. climbing stairs
   10. breathing

   ALSFRS = SUM (points for all 10 measures)

   Interpretation:

   minimum score: 0 maximum score: 40 The higher the score the more function is retained.

2. Efficacy: Inhibition of the disease progression - Norris scale [ Time Frame: 18 months ]

   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.

3. Efficacy: Inhibition of the disease progression - Forced vital capacity (FVC) [ Time Frame: 18 months ]
   FVC (%) will be measured at Visits I, and VI through X.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

No Contacts or Locations Provided

More Information

Publications of Results:

Syková E, Rychmach P, Drahorádová I, Konrádová Š, Růžičková K, Voříšek 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.

• Responsible Party: Bioinova, s.r.o.
• ClinicalTrials.gov Identifier: NCT03828123
• Other Study ID Numbers: AMSC-ALS-001
• First Posted: February 4, 2019
• Last Update Posted: February 12, 2019
• Last Verified: February 2019

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases