Clinical trial NCT03799718: Safety and Efficacy of Repeated Administration of NurOwn (MSC-NTF Cells) in Participants With Progressive MS
Official title: A Phase 2 Open-label Multicenter Study to Evaluate the Safety and Efficacy of Repeated Administration of NurOwn® [Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors (NTF), MSC-NTF] Cells in Participants With Progressive MS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Sclerosis, Chronic Progressive
Lead sponsor: Brainstorm-Cell Therapeutics
Sponsor class: INDUSTRY
First posted: 2019-01-10
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label
Primary purpose: TREATMENT

Brief 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.

Detailed description: An open-label study with a single treatment arm involving 20 participants with progressive MS at multiple investigational study sites. After providing informed consent, participants meeting the inclusion and exclusion criteria will be randomized and approximately 4 weeks later will undergo a bone-marrow aspiration (BMA). Each participants will receive three Intrathecal cell transplantations within 16 weeks and will be followed for 12 weeks for safety and efficacy.

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.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: Up to 28 weeks post-first treatment
Secondary outcomes:
measure: Number of Participants With 25% or Greater Improvement From Baseline in Time 25 Foot Walk (T25FW) Speed or Nine-Hole Peg Test (9-HPT)
timeFrame: From Baseline (pre-first treatment) to 28 weeks post-first treatment
measure: Number of Participants With 25% or Greater Improvement From Baseline to Week 28 in Timed 25 Foot Walk (T25FW) Speed
timeFrame: From Baseline (pre-first treatment) to 28 weeks post-first treatment
measure: Number of Participants With 25% or Greater Improvement From Baseline to Week 28 in 9-HPT
timeFrame: From Baseline (pre-first treatment) to 28 weeks post-first treatment
measure: Number of Participants Who Had >5.5 in Expanded Disability Status Scale (EDSS) at Baseline, With ≥0.5 Points Improvement From Baseline to Week 28
timeFrame: From Baseline (pre-first treatment) to 28 weeks post-first treatment
measure: Number of Participants With ≥10 Points Improvement From Baseline to Week 28 in Multiple Sclerosis Walking Scale (MSWS-12)
timeFrame: From Baseline (pre-first treatment) to 28 weeks post-first treatment
measure: Number of Participants With ≥8 Letter Improvement From Baseline to Week 28 in LCLA Binocular 2.5% Contrast Level
timeFrame: From Baseline (pre-first treatment) to 28 weeks post-first treatment
measure: Number of Participants With ≥ 3 Points Improvement From Baseline to Week 28 in Symbol Digit Modalities Test (SDMT) Score
timeFrame: From Baseline (pre-first treatment) to 28 weeks post-first treatment
measure: Change in Concentration of Vascular Endothelial Growth Factor (VEGF) Neuroprotective Biomarker From Baseline in the Cerebrospinal Fluid (CSF) 16 Weeks Following First NurOwn® Treatment
timeFrame: From Baseline (pre-first treatment) to 16 weeks post first treatment
measure: Change in Concentration of Hepatocyte Growth Factor (HGF) Neuroprotective Biomarker From Baseline in the Cerebrospinal Fluid (CSF) 16 Weeks Following NurOwn® Treatment
timeFrame: From Baseline (pre-first treatment) to 16 weeks post first treatment
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Redwood City
country: United States
facility: Stanford University School of Medicine
state: California
city: New York
country: United States
facility: The Mount Sinai Hospital
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Jeffrey Cohen, MD
role: PRINCIPAL_INVESTIGATOR
References: