Safety and Efficacy of Repeated Administration of NurOwn (MSC-NTF Cells) in Participants With Progressive MS
Condition: Multiple Sclerosis, Chronic Progressive
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive
Intervention: NurOwn (MSC-NTF cells)
Intervention description: Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Open label
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      A multidose open-label study with autologous Mesenchymal Stromal Stem Cells Secreting
      Neurotrophic Factors (MSC-NTF cells) involving 20 participants with progressive MS at
      multiple investigational study sites.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males and females ages 18 to 65 years old, inclusive, at the Screening Visit.

          2. Clinical diagnosis of Progressive MS (Primary and Secondary) based on the 2017 revised
             MacDonald Criteria and confirmation by the Investigator that the disease has entered
             the progressive stage for at least 6 months prior to enrollment.

          3. No evidence of clinical MS relapse or high dose pulse corticosteroid treatment within
             6 months prior to screening

          4. Disability status at screening with an Expanded Disability Status Scale (EDSS)
             3.0-6.5, inclusive.

          5. Able to walk 25 feet in 60 seconds or less.

          6. Stable dose of non-excluded MS Disease Modifying Therapy for at least 6 months prior
             to Screening Visit (Visit 1).

          7. Women of childbearing potential shall either be surgically sterile, or must agree not
             to become pregnant for the duration of the study. Women must be willing to undergo a
             serum pregnancy test at screening, and at the conclusion of the study. Participants of
             childbearing potential must agree to use a medically approved form of birth control
             (abstinence, intrauterine device (IUD), oral contraception, barrier and spermicide or
             hormonal implant) throughout the duration of the study and for at least 3 months
             following the last transplantation. For those women who are sexually active and using
             oral contraceptives, a second form of barrier contraception is required. Men must be
             willing to consistently use two forms of contraceptive if their partners are of
             childbearing age.

          8. Capable of providing informed consent and willing and able to follow study procedures,
             including willingness to undergo multiple/repeated lumbar puncture.

        Exclusion Criteria:

          1. Prior stem cell therapy of any kind.

          2. Active participation in any other MS interventional study or use of unapproved MS
             investigational therapy within 90 days prior to the Screening Visit (Visit 1).

          3. Inability to lie flat for the duration of intrathecal cell transplantation and/or bone
             marrow biopsy, or inability to tolerate study procedures for any other reason.

          4. History of clinically significant autoimmune disease (excluding thyroid disease) that
             may confound study results, in the opinion of the Investigator and the medical
             monitor, myelodysplastic or myeloproliferative disorder, leukemia or lymphoma, whole
             body irradiation, hip fracture, or severe scoliosis.

          5. Any unstable clinically significant medical condition other than multiple sclerosis
             (e.g., within six months of Screening Visit (Visit 1), had myocardial infarction,
             angina pectoris, and/or congestive heart failure), treatment with anticoagulants that,
             in the opinion of the investigator, would compromise the safety of participants.

          6. Any history of malignancy within the previous 5 years, except for non-melanoma
             localized skin cancers (with no evidence of metastasis, significant invasion, or
             reoccurrence within three years of Screening Visit (Visit 1)).

          7. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value >3.0
             times the upper normal limit.

          8. Serum creatinine value >2.0 times the upper normal limit.

          9. Positive test for Hepatitis B (HBV; surface antigen (HBsAg) and antibodies to core
             antigen (IgG and IgM anti-HBc)), Hepatitis C (HCV), or human immunodeficiency virus
             (HIV) 1 and 2.

         10. Current use of immunosuppressant medication or use of such medication within 6 months
             of study enrollment (aside from Rituximab or other approved B-cell immunotherapy).
             Alemtuzumab (Lemtrada), Cladribine (NDA submitted), Natalizumab (Tysabri), S1P
             modulators (Gilenya) are excluded for safety reasons due to the known risk of systemic
             autoimmune disease, malignancy, opportunistic infections, and cardiovascular toxicity
             associated with these therapies, as well as theoretical effects on MSC-NTF cell homing
             and migration, that may be associated with Natalizumab and/or S1P modulators
             (Gilenya).

         11. Any history of acquired or inherited immune deficiency syndrome.

         12. Any history of either substance abuse within the past year, or unstable psychiatric
             disease according to the Investigator's judgment.

         13. Pregnant women or women currently breastfeeding.

         14. Subjects for whom MRI is contraindicated (i.e., have a pacemaker or other metallic
             implanted device, or are unable to remain in the machine for period of time needed to
             acquire a scan.