Clinical trial NCT05080270: Feasibility Study of Tolerogenic Fibroblasts in Patients With Refractory Multiple Sclerosis
Official title: Feasibility Study of Tolerogenic Fibroblasts in Patients With Refractory Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Multiple Sclerosis, Relapsing-Remitting
Multiple Sclerosis
Keywords: MS
Cell Therapy
Fibroblasts
Fibrobiologics
Stem cells
regenerative medicine
tissue regeneration
Immune modulation
Lead sponsor: FibroBiologics
Sponsor class: OTHER
First posted: 2021-10-15
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Detailed description: 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. Mechanistically, tolerogenic fibroblasts produce anti-inflammatory and immune modulatory factors, which appear to be therapeutic in the context of autoimmunity, including IL-10 and TGF-beta. Additionally, tolerogenic fibroblasts produce neurotrophic mediators that enhance myelin production and/or prevent neuronal apoptosis.

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.

Eligibility criteria: Inclusion Criteria:

1. Patients willing to sign an informed consent and capable of understanding the features of this clinical trial.
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:

1. Patients with evidence of active proliferative retinopathy.
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

Primary outcomes:
measure: Safety: Adverse even monitoring of subjects for 4 hours after infusion
timeFrame: Monitoring during the Intravenous infusion of allogeneic tolerogenic fibroblasts, and continued for 4 hours after infusion
measure: Safety: Complete Blood Count to monitor inflammation markers
timeFrame: Day before infusion to establish a baseline, week 8, and week 16 after infusion
measure: Safety: Serum chemistry to monitor impact on serum chemistry
timeFrame: Day before infusion to establish a baseline, week 8, and week 16 after infusion
measure: Safety: 12-lead Electrocardiogram (ECG) to monitor cardiovascular health
timeFrame: Day before infusion to establish a baseline, week 8, and week 16 after infusion
Secondary outcomes:
measure: Efficacy: Expanded Disability Status Scale (EDSS) to quantify disability scale and monitors changes
timeFrame: Day before infusion to establish a baseline, week 8, and week 16 after infusion
measure: Efficacy: Paced Auditory Serial Addition Test (PASAT) to measure cognitive function and processing speed
timeFrame: Day before infusion to establish a baseline, week 8, and week 16 after infusion
measure: Efficacy: Nine-Hole Peg Test to measure and quantify upper extermity function
timeFrame: Day before infusion to establish a baseline, week 8, and week 16 after infusion
measure: Efficacy: Timed 25-Foot Walk Test to quantify mobility and leg function
timeFrame: Day before infusion to establish a baseline, week 8, and week 16 after infusion
measure: Efficacy: Gadolinium Enhanced MRI to detect demyelinated areas of the nerves
timeFrame: Day before infusion to establish a baseline, and week 16 after infusion
Other outcomes:
Locations:
city: Tijuana
country: Mexico
facility: Servicios Medicos UCC, S.C.
state: Baja California
Study officials:
affiliation: FibroBiologics
name: Hamid Khoja, Ph.D.
role: STUDY_DIRECTOR
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