Feasibility Study of Tolerogenic Fibroblasts in Patients With Refractory Multiple Sclerosis (MSFibroblast)

October 14, 2021 updated by: FibroBiologics

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
    • Baja California
      • Tijuana, Baja California, Mexico, 22504
        • Servicios Medicos UCC, S.C.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: tolerogenic fibroblasts administered via intravenous infusion
A single dose of 100 million tolerogenic fibroblasts administered via intravenous infusion.
Biological: Tolerogenic Fibroblasts
administrating single dose of 100 million tolerogenic fibroblasts via intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety: Adverse even monitoring of subjects for 4 hours after infusion
Time Frame: Monitoring during the Intravenous infusion of allogeneic tolerogenic fibroblasts, and continued 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
Time Frame: Day before infusion to establish a baseline, week 8, and week 16 after infusion
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
Time Frame: Day before infusion to establish a baseline, week 8, and week 16 after infusion
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
Time Frame: Day before infusion to establish a baseline, week 8, and week 16 after infusion
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy: Expanded Disability Status Scale (EDSS) to quantify disability scale and monitors changes
Time Frame: Day before infusion to establish a baseline, week 8, and week 16 after infusion
The Expanded Disability Status Scale (EDSS) quantifies disability in multiple sclerosis and monitors changes in the level of disability over time. The test is based on neurological examination and impact on Functional Systems representing network of neurons in the brain. It is widely used in clinical trials and the assessment of people with MS. The scale was developed by a neurologist called John Kurtzke in 1983 as an advance from his previous 10 step Disability Status Scale (DSS). The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist.
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
Time Frame: Day before infusion to establish a baseline, week 8, and week 16 after infusion
PASAT is a measure of cognitive function that assesses auditory information processing speed, flexibility, and calculation ability. The test was developed by Gronwell in 1977 and later adapted by Rao and colleagues in 1989 for use in MS. The PASAT is presented using audio cassette tape or compact disk to ensure standardization in the rate of stimulus presentation. In the test, single digits are presented every 3 seconds, and the patient must add each new digit to the one immediately prior to it. Shorter inter-stimulus intervals, e.g., 2 seconds or less, have also been used with the PASAT but tend to increase the difficulty of the task.
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
Time Frame: Day before infusion to establish a baseline, week 8, and week 16 after infusion
The 9-HPT is a brief, standardized, quantitative test of upper extremity function. Both the dominant and non-dominant hands are tested twice. The patient is seated at a table with a small, shallow container holding nine pegs and a wood or plastic block containing nine empty holes. On a start command when a stopwatch is started, the patient picks up the nine pegs one at a time as quickly as possible, puts them in the nine holes, and, once they are in the holes, removes them again as quickly as possible one at a time, replacing them into the shallow container. The total time to complete the task is recorded. Two consecutive trials with the dominant hand are immediately followed by two consecutive trials with the non-dominant hand.
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
Time Frame: Day before infusion to establish a baseline, week 8, and week 16 after infusion
The T25-FW is a quantitative mobility and leg function performance test based on a timed 25-walk. The patient is directed to one end of a clearly marked 25-foot course and is instructed to walk 25 feet as quickly as possible but safely. The time is calculated from the initiation of the instruction to start and ends when the patient has reached the 25-foot mark. The task is immediately administered again by having the patient walk back the same distance. Patients may use assistive devices when doing this task.
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
Time Frame: Day before infusion to establish a baseline, and week 16 after infusion
Gadolinium Enhanced MRI is used to detect demyelinated areas of the nerves in the brain and cervical spinal cord. These Damaged areas can be observed by MRI presented as plaques, and the intensity of the plaques can determine the age of multiple sclerosis caused lesions.
Day before infusion to establish a baseline, and week 16 after infusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

FibroBiologics

Investigators

  • Study Director: Hamid Khoja, Ph.D., FibroBiologics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 21, 2020

Primary Completion (Actual)

June 8, 2021

Study Completion (Actual)

June 8, 2021

Study Registration Dates

First Submitted

October 5, 2021

First Submitted That Met QC Criteria

October 5, 2021

First Posted (Actual)

October 15, 2021

Study Record Updates

Last Update Posted (Actual)

October 22, 2021

Last Update Submitted That Met QC Criteria

October 14, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Fibroblast_MS_safety2021

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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