Feasibility Study of Tolerogenic Fibroblasts in Patients With Refractory Multiple Sclerosis

NCT05080270 | Completed Early Phase 1

• 1 other identifier: Fibroblast_MS_safety2021
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Fibroblasts have demonstrated potent immune modulatory and therapeutic activity in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, as well as in other models of autoimmune and inflammatory diseases. 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.

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Keywords

MS; Cell Therapy; Fibroblasts; Fibrobiologics; Stem cells; regenerative medicine; tissue regeneration; Immune modulation

Outcome Measures

Primary Outcomes (4)

• Safety: Adverse even monitoring of subjects for 4 hours after infusion

  Monitor subjects for possible treatment-related acute immune symptoms or vascular occlusion symptoms during the administration of the allogeneic tolerogenic fibroblasts via intravenous infusion.

  Monitoring during the Intravenous infusion of allogeneic tolerogenic fibroblasts, and continued for 4 hours after infusion

• Safety: Complete Blood Count to monitor inflammation markers

  Complete Blood Count used to monitor inflammation markers included white blood cell (WBC), neutrophil (N), lymphocyte (L), neutrophil-lymphocyte ratio (NLR), mean platelet volume (MPV), and platelet-lymphocyte ratio. This safety test is to monitor subjects for inflammation during the course of the study, relating to the course of the disease, or allogeneic tolerogenic fibroblasts administered through Intravenous infusion

  Day before infusion to establish a baseline, week 8, and week 16 after infusion

• Safety: Serum chemistry to monitor impact on serum chemistry

  This test will measure the amount of certain substances in serum samples, including electrolytes (such as sodium, potassium, and chloride), fats, proteins, glucose (sugar), and enzymes. Blood chemistry tests give essential information about how well a person's kidneys, liver, and other organs are working. An abnormal amount of a substance in the blood can be a sign of disease or a side effect of treatment. Blood chemistry tests help diagnose and monitor many conditions before, during, and after treatment. Also called blood chemistry study.

  Day before infusion to establish a baseline, week 8, and week 16 after infusion

• Safety: 12-lead Electrocardiogram (ECG) to monitor cardiovascular health

  A 12-lead electrocardiogram will be used to monitor the baseline cardiovascular health of the participants and continue to monitor their cardiovascular health during the course of the study measuring heart rate, blood pressure, ventricular rate, PR interval, RP interval, QRS interval, and GT interval. This safety test is to monitor the subjects for cardiac events related to the course of the disease, or allogeneic tolerogenic fibroblasts administered through Intravenous infusion

  Day before infusion to establish a baseline, week 8, and week 16 after infusion

Secondary Outcomes (5)

• Efficacy: Expanded Disability Status Scale (EDSS) to quantify disability scale and monitors changes

  Day before infusion to establish a baseline, week 8, and week 16 after infusion

• Efficacy: Paced Auditory Serial Addition Test (PASAT) to measure cognitive function and processing speed

  Day before infusion to establish a baseline, week 8, and week 16 after infusion

• Efficacy: Nine-Hole Peg Test to measure and quantify upper extermity function

  Day before infusion to establish a baseline, week 8, and week 16 after infusion

• Efficacy: Timed 25-Foot Walk Test to quantify mobility and leg function

  Day before infusion to establish a baseline, week 8, and week 16 after infusion

• Efficacy: Gadolinium Enhanced MRI to detect demyelinated areas of the nerves

  Day before infusion to establish a baseline, and week 16 after infusion

Study Arms (1)

tolerogenic fibroblasts administered via intravenous infusion

EXPERIMENTAL

A single dose of 100 million tolerogenic fibroblasts administered via intravenous infusion.

Biological: Tolerogenic Fibroblasts

Interventions

Tolerogenic Fibroblasts BIOLOGICAL

administrating single dose of 100 million tolerogenic fibroblasts via intravenous infusion

tolerogenic fibroblasts administered via intravenous infusion

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients willing to sign an informed consent and capable of understanding the features of this clinical trial.
• Willing to keep a weekly diary and undergo observation for four months
• 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.
• EDSS scores of 2·0 to 5·5 points assessed at least three months after the last acute attack of MS.

You may not qualify if:

• Patients with evidence of active proliferative retinopathy.
• Patients with poorly controlled diabetes mellitus (HbA1C \> 8.5%).
• Patients with renal insufficiency (Creatinine \> 2.5) or failure.
• Infection as evidenced by WBC count of \>15,000 k/cumm and/or temperature \>38C.
• History of organ transplant.
• History of previous or active malignancy, except for localized cutaneous basal or squamous cell carcinoma or carcinoma in situ of the cervix
• History of sickle cell anemia
• Cardiovascular conditions:
• Exercise limiting angina ( Canadian Cardiovascular Society Class greater or equal to 3
• Congestive heart failure (New York Heart Association class greater or equal to 3
• Unstable angina
• Acute ST elevation myocardial infarction (MI) within one month
• Transient ischemic attack or stroke within one month
• Severe valvular disease

Sponsors & Collaborators

• FibroBiologics: lead

Study Sites (1)

Servicios Medicos UCC, S.C.

Tijuana, Estado de Baja California, 22504, Mexico

Location

Related Publications (17)

• Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, Du MQ, Luan SL, Altmann DR, Thompson AJ, Compston A, Scott MA, Miller DH, Chandran S. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol. 2012 Feb;11(2):150-6. doi: 10.1016/S1474-4422(11)70305-2. Epub 2012 Jan 10.

  PMID: 22236384 BACKGROUND

• 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.

  PMID: 16702830 BACKGROUND

• Evans C, Beland SG, Kulaga S, Wolfson C, Kingwell E, Marriott J, Koch M, Makhani N, Morrow S, Fisk J, Dykeman J, Jette N, Pringsheim T, Marrie RA. Incidence and prevalence of multiple sclerosis in the Americas: a systematic review. Neuroepidemiology. 2013;40(3):195-210. doi: 10.1159/000342779. Epub 2013 Jan 24.

  PMID: 23363936 BACKGROUND

• 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.

  PMID: 28367411 BACKGROUND

• Navikas V, Link H. Review: cytokines and the pathogenesis of multiple sclerosis. J Neurosci Res. 1996 Aug 15;45(4):322-33. doi: 10.1002/(SICI)1097-4547(19960815)45:43.0.CO;2-B.

  PMID: 8872892 BACKGROUND

• Marrie RA, Elliott L, Marriott J, Cossoy M, Blanchard J, Leung S, Yu N. Effect of comorbidity on mortality in multiple sclerosis. Neurology. 2015 Jul 21;85(3):240-7. doi: 10.1212/WNL.0000000000001718. Epub 2015 May 27.

  PMID: 26019190 BACKGROUND

• Goldman MD, Motl RW, Rudick RA. Possible clinical outcome measures for clinical trials in patients with multiple sclerosis. Ther Adv Neurol Disord. 2010 Jul;3(4):229-39. doi: 10.1177/1756285610374117.

  PMID: 21179614 BACKGROUND

• 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.

  PMID: 14313512 BACKGROUND

• Polman CH, Rudick RA. The multiple sclerosis functional composite: a clinically meaningful measure of disability. Neurology. 2010 Apr 27;74 Suppl 3:S8-15. doi: 10.1212/WNL.0b013e3181dbb571.

  PMID: 20421572 BACKGROUND

• Rodgers JM, Robinson AP, Miller SD. Strategies for protecting oligodendrocytes and enhancing remyelination in multiple sclerosis. Discov Med. 2013 Aug;16(86):53-63.

  PMID: 23911232 BACKGROUND

• Ernstsson O, Gyllensten H, Alexanderson K, Tinghog P, Friberg E, Norlund A. Cost of Illness of Multiple Sclerosis - A Systematic Review. PLoS One. 2016 Jul 13;11(7):e0159129. doi: 10.1371/journal.pone.0159129. eCollection 2016.

  PMID: 27411042 BACKGROUND

• 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.

  PMID: 25911108 BACKGROUND

• Frampton JE. Ocrelizumab: First Global Approval. Drugs. 2017 Jun;77(9):1035-1041. doi: 10.1007/s40265-017-0757-6.

  PMID: 28523586 BACKGROUND

• Offner H, Sinha S, Burrows GG, Ferro AJ, Vandenbark AA. RTL therapy for multiple sclerosis: a Phase I clinical study. J Neuroimmunol. 2011 Feb;231(1-2):7-14. doi: 10.1016/j.jneuroim.2010.09.013. Epub 2010 Oct 20.

  PMID: 20965577 BACKGROUND

• 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.

  PMID: 20937945 BACKGROUND

• 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.

  PMID: 20427749 BACKGROUND

• Bielekova B, Richert N, Howard T, Packer AN, Blevins G, Ohayon J, McFarland HF, Sturzebecher CS, Martin R. Treatment with the phosphodiesterase type-4 inhibitor rolipram fails to inhibit blood--brain barrier disruption in multiple sclerosis. Mult Scler. 2009 Oct;15(10):1206-14. doi: 10.1177/1352458509345903. Epub 2009 Sep 23.

  PMID: 19776093 BACKGROUND

Related Links

• EDSS description
• Multiple Sclerosis overview
• Diagnosing Multiple Sclerosis and Evaluating Disease Activity

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Hamid Khoja, Ph.D.

  FibroBiologics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The proposed study will assess primary safety and secondary efficacy endpoints of allogeneic tolerogenic fibroblasts administered through Intravenous infusion at a single dose of 100 million cells to 5 patients with relapsing remitting MS resistant to interferon.

Study Record Dates

• First Submitted: October 5, 2021
• First Posted: October 15, 2021
• Study Start: September 21, 2020
• Primary Completion: June 8, 2021
• Study Completion: June 8, 2021
• Last Updated: October 22, 2021

Record last verified: 2021-10

Locations

ME (1)