Feasibility Study of Tolerogenic Fibroblasts in Patients With Refractory Multiple Sclerosis
NCT ID: NCT05080270
Last Updated: 2021-10-22
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
EARLY_PHASE1
5 participants
INTERVENTIONAL
2020-09-21
2021-06-08
Brief Summary
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This study will assess primary safety and secondary efficacy endpoints of intravenous administration of 100 million tolerogenic fibroblasts to 5 patients with relapsing remitting MS resistant to interferon. While the safety of fibroblasts administered clinically is established, it is unknown whether these cells are effective in the treatment of multiple sclerosis (MS).
Our hypothesis is that the tolerogenic fibroblasts will be well-tolerated and meet our primary objective. In addition, The investigators are optimistic that they will see signs of efficacy based on the following: Neurological assessment of the MS functional composite assessment which comprises of EDSS, the expanded EDSS (Rating Neurologic Impairment in Multiple Sclerosis, the Scripps neurological rating scale (NRS), paced auditory serial addition test (PASAT), the nine-hole peg test, and 25-foot walking time, short-form 36 (SF-36) quality of life questionnaire and gadolinium-enhanced MRI scans of the brain and cervical spinal cord.
Detailed Description
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This study will assess primary safety and secondary efficacy endpoints of intravenous administration of 100 million tolerogenic fibroblasts to 5 patients with relapsing remitting MS resistant to interferon. While the safety of fibroblasts administered clinically is established, it is unknown whether these cells are effective in the treatment of multiple sclerosis (MS).
Research Hypothesis: Intravenous administration of 100 million tolerogenic fibroblasts will be well tolerated and induce a therapeutic effect in relapse remitting MS patients.
Rationale: The family of Mesenchymal Stem Cells (MSCs) is immune-modulatory, and bone marrow MSCs (BM-MSCs) have induced therapeutic responses in patients with MS \[1\]. Tolerogenic fibroblasts possess superior immune modulatory activity compared to BM-MSCs and adipose MSCs. The investigators, therefore, seek to perform a five-patient trial to assess the safety and signs of efficacy of this cell population in MS patients resistant to interferon.
The trial's primary objective is freedom from treatment-associated adverse events at 1, 2, 4, 8, and 16 weeks post-treatment. The study's secondary objective will be efficacy as assessed at baseline, weeks 2, 4, 8, and 16. The results will be quantified based on the following: Neurological assessment of the MS functional composite assessment, which comprises of EDSS, the expanded EDSS (Rating Neurologic Impairment in Multiple Sclerosis, the Scripps neurological rating scale (NRS), paced auditory serial addition test (PASAT), the nine-hole peg test, and 25-foot walking time, short-form 36 (SF-36) quality of life questionnaire and gadolinium-enhanced MRI scans of the brain and cervical spinal cord.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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tolerogenic fibroblasts administered via intravenous infusion
A single dose of 100 million tolerogenic fibroblasts administered via intravenous infusion.
Tolerogenic Fibroblasts
administrating single dose of 100 million tolerogenic fibroblasts via intravenous infusion
Interventions
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Tolerogenic Fibroblasts
administrating single dose of 100 million tolerogenic fibroblasts via intravenous infusion
Eligibility Criteria
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Inclusion Criteria
2. Willing to keep a weekly diary and undergo observation for four months
3. Non-pregnant patients 18-55 years of age with MS according to the revised McDonald criteria and meeting the Possner criteria for clinically defined MS.
4. EDSS scores of 2·0 to 5·5 points assessed at least three months after the last acute attack of MS.
Exclusion Criteria
2. Patients with poorly controlled diabetes mellitus (HbA1C \> 8.5%).
3. Patients with renal insufficiency (Creatinine \> 2.5) or failure.
4. Infection as evidenced by WBC count of \>15,000 k/cumm and/or temperature \>38C.
5. History of organ transplant.
6. History of previous or active malignancy, except for localized cutaneous basal or squamous cell carcinoma or carcinoma in situ of the cervix
7. History of sickle cell anemia
8. Cardiovascular conditions:
1. Exercise limiting angina ( Canadian Cardiovascular Society Class greater or equal to 3
2. Congestive heart failure (New York Heart Association class greater or equal to 3
3. Unstable angina
4. Acute ST elevation myocardial infarction (MI) within one month
5. Transient ischemic attack or stroke within one month
6. Severe valvular disease
18 Years
55 Years
ALL
No
Sponsors
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FibroBiologics
OTHER
Responsible Party
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Principal Investigators
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Hamid Khoja, Ph.D.
Role: STUDY_DIRECTOR
FibroBiologics
Locations
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Servicios Medicos UCC, S.C.
Tijuana, Estado de Baja California, Mexico
Countries
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References
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Kantarci O, Wingerchuk D. Epidemiology and natural history of multiple sclerosis: new insights. Curr Opin Neurol. 2006 Jun;19(3):248-54. doi: 10.1097/01.wco.0000227033.47458.82.
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Ghasemi N, Razavi S, Nikzad E. Multiple Sclerosis: Pathogenesis, Symptoms, Diagnoses and Cell-Based Therapy. Cell J. 2017 Apr-Jun;19(1):1-10. doi: 10.22074/cellj.2016.4867. Epub 2016 Dec 21.
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SCHUMACHER GA, BEEBE G, KIBLER RF, KURLAND LT, KURTZKE JF, MCDOWELL F, NAGLER B, SIBLEY WA, TOURTELLOTTE WW, WILLMON TL. PROBLEMS OF EXPERIMENTAL TRIALS OF THERAPY IN MULTIPLE SCLEROSIS: REPORT BY THE PANEL ON THE EVALUATION OF EXPERIMENTAL TRIALS OF THERAPY IN MULTIPLE SCLEROSIS. Ann N Y Acad Sci. 1965 Mar 31;122:552-68. doi: 10.1111/j.1749-6632.1965.tb20235.x. No abstract available.
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Hartung DM, Bourdette DN, Ahmed SM, Whitham RH. The cost of multiple sclerosis drugs in the US and the pharmaceutical industry: Too big to fail? Neurology. 2015 May 26;84(21):2185-92. doi: 10.1212/WNL.0000000000001608. Epub 2015 Apr 24.
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Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, Bulte JW, Petrou P, Ben-Hur T, Abramsky O, Slavin S. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2010 Oct;67(10):1187-94. doi: 10.1001/archneurol.2010.248.
Burton JM, Kimball S, Vieth R, Bar-Or A, Dosch HM, Cheung R, Gagne D, D'Souza C, Ursell M, O'Connor P. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology. 2010 Jun 8;74(23):1852-9. doi: 10.1212/WNL.0b013e3181e1cec2. Epub 2010 Apr 28.
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Related Links
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EDSS description
Multiple Sclerosis overview
Diagnosing Multiple Sclerosis and Evaluating Disease Activity
Other Identifiers
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Fibroblast_MS_safety2021
Identifier Type: -
Identifier Source: org_study_id