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

• Register: ClinicalTrials.gov
• Last refreshed on: 11 December 2023
• Main ID: NCT03799718
• Date of registration: 07/01/2019
• Prospective Registration: Yes
• Primary sponsor: Brainstorm-Cell Therapeutics
• Public title: Safety and Efficacy of Repeated Administration of NurOwn (MSC-NTF Cells) in Participants With Progressive MS
• Scientific 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
• Date of first enrolment: March 13, 2019
• Target sample size: 23
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03799718
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Jeffrey Cohen, MD
• Affiliation: The Cleveland Clinic

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Sclerosis, Chronic Progressive

Intervention(s)

Biological: NurOwn (MSC-NTF cells)

Primary Outcome(s)

Number of Participants With Treatment-emergent Adverse Events [Time Frame: Up to 28 weeks post-first treatment]

Secondary Outcome(s)

Number of Participants With =10 Points Improvement From Baseline to Week 28 in Multiple Sclerosis Walking Scale (MSWS-12) [Time Frame: From Baseline (pre-first treatment) to 28 weeks post-first treatment]

Change in Concentration of Vascular Endothelial Growth Factor (VEGF) Neuroprotective Biomarker From Baseline in the Cerebrospinal Fluid (CSF) 16 Weeks Following First NurOwn® Treatment [Time Frame: From Baseline (pre-first treatment) to 16 weeks post first treatment]

Number of Participants With = 3 Points Improvement From Baseline to Week 28 in Symbol Digit Modalities Test (SDMT) Score [Time Frame: From Baseline (pre-first treatment) to 28 weeks post-first treatment]

Number of Participants With =8 Letter Improvement From Baseline to Week 28 in LCLA Binocular 2.5% Contrast Level [Time Frame: From Baseline (pre-first treatment) to 28 weeks post-first treatment]

Number of Participants With 25% or Greater Improvement From Baseline in Time 25 Foot Walk (T25FW) Speed or Nine-Hole Peg Test (9-HPT) [Time Frame: From Baseline (pre-first treatment) to 28 weeks post-first treatment]

Number of Participants With 25% or Greater Improvement From Baseline to Week 28 in Timed 25 Foot Walk (T25FW) Speed [Time Frame: From Baseline (pre-first treatment) to 28 weeks post-first treatment]

Change in Concentration of Hepatocyte Growth Factor (HGF) Neuroprotective Biomarker From Baseline in the Cerebrospinal Fluid (CSF) 16 Weeks Following NurOwn® Treatment [Time Frame: From Baseline (pre-first treatment) to 16 weeks post first treatment]

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 [Time Frame: From Baseline (pre-first treatment) to 28 weeks post-first treatment]

Number of Participants With 25% or Greater Improvement From Baseline to Week 28 in 9-HPT [Time Frame: From Baseline (pre-first treatment) to 28 weeks post-first treatment]

Secondary ID(s)

BCT-101-US

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 14/11/2022
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03799718