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

Primary Purpose

Motor Neuron Disease, Amyotrophic Lateral Sclerosis

Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Suspension of human autologous MSC 3P in 1.5 ml
Sponsored by
Bioinova, s.r.o.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Motor Neuron Disease, Amyotrophic Lateral Sclerosis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Autologous Multipotent MSC

    Arm Description

    Patients with intrathecal administration of Suspension of human autologous MSC 3P in 1.5 ml

    Outcomes

    Primary Outcome Measures

    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.

    Secondary Outcome Measures

    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.
    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.
    Efficacy: Inhibition of the disease progression - Forced vital capacity (FVC)
    FVC (%) will be measured at Visits I, and VI through X.

    Full Information

    First Posted
    July 20, 2017
    Last Updated
    February 11, 2019
    Sponsor
    Bioinova, s.r.o.
    Collaborators
    Department of Neurology, University Hospital Motol, Prague, Czech Republic
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03828123
    Brief Title
    Autologous Multipotent Mesenchymal Stromal Cells in the Treatment of Amyotrophic Lateral Sclerosis
    Acronym
    AMSC-ALS-001
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2019
    Overall Recruitment Status
    Completed
    Study Start Date
    January 2012 (Actual)
    Primary Completion Date
    August 18, 2017 (Actual)
    Study Completion Date
    August 18, 2017 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Bioinova, s.r.o.
    Collaborators
    Department of Neurology, University Hospital Motol, Prague, Czech Republic

    4. Oversight

    Data Monitoring Committee
    No

    5. 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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Motor Neuron Disease, Amyotrophic Lateral Sclerosis

    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
    26 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Autologous Multipotent MSC
    Arm Type
    Experimental
    Arm Description
    Patients with intrathecal administration of Suspension of human autologous MSC 3P in 1.5 ml
    Intervention Type
    Biological
    Intervention Name(s)
    Suspension of human autologous MSC 3P in 1.5 ml
    Intervention Description
    Intrathecal application of Autologous Multipotent Mesenchymal Stromal Cells 3P suspension
    Primary Outcome Measure Information:
    Title
    Safety: Complications related to the medicinal product application - new neurological deficit and occurrence of other adverse events
    Description
    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.
    Time Frame
    1 year
    Secondary Outcome Measure Information:
    Title
    Efficacy: Inhibition of the disease progression - ALS functional rating scale
    Description
    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.
    Time Frame
    18 months
    Title
    Efficacy: Inhibition of the disease progression - Norris scale
    Description
    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.
    Time Frame
    18 months
    Title
    Efficacy: Inhibition of the disease progression - Forced vital capacity (FVC)
    Description
    FVC (%) will be measured at Visits I, and VI through X.
    Time Frame
    18 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: established diagnosis of definite ALS according to El Escorial criteria riluzole naive or stable dose for at least 2 months, life expectancy more than 2 years patients able to provide written informed consent. Exclusion Criteria: FVC less than 70% in case of primary bulbar paralysis less than 15 points on Norris bulbar scale, less than 15 points on Norris spinal scale, pregnancy, breastfeeding coagulopathy, skin infection at the site of bone marrow aspiration or application of the cell product, gastrostomy, 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 .....), alcohol or drug abuse cancer. 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 fertile men not using proven contraceptive measures including effective contraception of their partner (established oral contraception, intrauterine device, ligation of the uterine tube)

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    27938483
    Citation
    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.
    Results Reference
    result

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    Autologous Multipotent Mesenchymal Stromal Cells in the Treatment of Amyotrophic Lateral Sclerosis

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