Safety and Efficacy of Repeated Administration of NurOwn (MSC-NTF Cells) in Participants With Progressive MS

• ClinicalTrials.gov Identifier: NCT03799718
• Recruitment Status: Recruiting
• First Posted: January 10, 2019
• Last Update Posted: July 23, 2019
• Sponsor: Brainstorm-Cell Therapeutics
• Information provided by (Responsible Party): Brainstorm-Cell Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis, Chronic Progressive	Biological: NurOwn (MSC-NTF cells)	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open label
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 13, 2019
• Estimated Primary Completion Date: February 2020
• Estimated Study Completion Date: September 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: NurOwn (MSC-NTF cells); Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors	Biological: NurOwn (MSC-NTF cells); Autologous Mesenchymal Stem Cells Secreting Neurotrophic Factors

Outcome Measures

Primary Outcome Measures :

1. Incidence of treatment-emergent adverse events [ Time Frame: Up to 28 weeks post-treatment ]
   Safety of 3 intrathecal doses of NurOwn® (MSC-NTF cells)

Secondary Outcome Measures :

1. Timed 25-foot walking speed or 9-Hole Peg Test - change from baseline. [ Time Frame: 28 weeks ]
   Efficacy measure
2. Number of participants with changes in neurotrophic factors (such as Vascular endothelial growth factor and Hepatocyte growth factor) in the cerebrospinal fluid (CSF) following NurOwn® transplantation [ Time Frame: 16 weeks post treatment ]
   Efficacy measure

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. 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).

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, 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.

Contacts and Locations

Contacts

Contact: Ralph Kern, MD; 201-488-0460; rkern@brainstorm-cell.com

Contact: Yael Gothelf, Ph.D.; ygothelf@brainstorm-cell.com

Locations

United States, California

Stanford University School of Medicine; Recruiting

Redwood City, California, United States, 943063

Contact: Yamuna Joseph yamuna@stanford.edu

Contact: Viktoriya Bourakova viktoriya.bourakova@stanford.edu

United States, Ohio

Cleveland Clinic; Active, not recruiting

Cleveland, Ohio, United States, 44195

Sponsors and Collaborators

Brainstorm-Cell Therapeutics

Investigators

• Principal Investigator: Jeffrey Cohen, MD; The Cleveland Clinic

More Information

• Responsible Party: Brainstorm-Cell Therapeutics
• ClinicalTrials.gov Identifier: NCT03799718
• Other Study ID Numbers: BCT-101-US
• First Posted: January 10, 2019
• Last Update Posted: July 23, 2019
• Last Verified: January 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases