Study to Investigate the Safety of the Transplantation of Human Glial Restricted Progenitor Cells Into Subjects With Transverse Myelitis

Brief Title

Study to Investigate the Safety of the Transplantation of Human Glial Restricted Progenitor Cells Into Subjects With Transverse Myelitis

Official Title

A Phase 1/2a Open-Label Study to Investigate the Safety of the Transplantation (by Injection) of Human Glial Restricted Progenitor Cells (hGRPs; Q-Cells®) Into Subjects With Transverse Myelitis (TM)

Brief Summary

      This study is a non-randomized, open-label, partially blinded, sequential cohort,
      dose-escalation study designed to obtain preliminary data on the safety, tolerability, and
      early activity of Q-Cells® transplantation in subjects with Transverse Myelitis. For each of
      the dose levels, transplantation of Q-Cells® unilaterally into spinal cord demyelinated
      lesions will be evaluated. Subjects will be blinded to side of treatment.

      Idiopathic Transverse Myelitis is a monophasic disorder characterized predominantly by
      demyelination. Patients are left with disability from damage to ascending and descending
      white matter tracts. Q-Cells® are comprised of glial progenitor cells.It is postulated that
      the Q-Cells® glial progeny (healthy astrocytes and oligodendrocytes) will integrate into the
      spinal cord lesion site and remyelinate demyelinated axons as well as provide trophic support
      for damaged axons. Therefore, Q-Cells® have the potential to repair damage that has occurred
      and could be clinically useful for patients with disability caused by TM.

      The study is planned to enroll up to 9 subjects. Each subject will be followed for 9 months
      after transplantation of Q-Cells®. Each subject will receive a single time point
      administration of Q-Cells®: with transplantation foci targeted to posterior columns in the
      spinal cord (all transplantation foci below C7) on one side.

      Study participation consists of Screening, Pre-operative/Treatment, and Post-treatment study
      periods that will generally last from 9 to 12 months in total. The study data will be
      assessed for safety and activity until the last subject has completed the 9-month study
      visit. Following completion of the 9-month follow-up period, subjects who consent will
      continue to be followed for safety and activity in a separate long-term follow-up protocol.
    


Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability].

Secondary Outcome

 Scores on American Spinal Injury Association (ASIA) scale testing including motor and sensory evaluations

Condition

Transverse Myelitis

Intervention

Q-Cells

Study Arms / Comparison Groups

 Q-Cells dose level 1
Description:  One time surgical transplantation of Q-Cells dose level 1 unilaterally into spinal cord demyelinated lesion

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

9

Start Date

March 20, 2021

Completion Date

June 2024

Primary Completion Date

June 2023

Eligibility Criteria

        Inclusion Criteria:

          1. Ability to understand the purpose and risks of the study and provide signed and dated
             informed consent and authorization to collect and use protected health information
             (PHI) in accordance with national and local subject privacy regulations.

          2. Live within reasonable travel distance to center or have reliable mechanism to travel
             to the center.

          3. Have a caregiver willing/able to assist in the transportation and care required by
             study participation.

          4. Subject is 18 - 70 years of age (inclusive) on day of Screening Visit.

          5. Subject is diagnosed with idiopathic TM within the past 120 months in accord with the
             Transverse Myelitis Consortium Working Group (2002).

          6. Subject has a MRI with a single focus of T2 hyperintensity that is 4 to 10 cm in
             length if no post contrast enhancement seen, or a single focus T1 post contrast
             enhancing lesion of 4 to 10 cm, with its most rostral extent at or below C8
             myotome/dermatome level.

          7. Subject has negative NMO IgG (anti-AQP4) test at two separate time points, separated
             by at least 6 months.

          8. Subject has brain MRI not consistent with multiple sclerosis or other autoimmune or
             demyelinating disease.

          9. Subject is more than 12 months from TM onset.

         10. Subject has ASIA A categorization.

         11. Subject's neurological deficits related to TM have been stable for at least 3 months.

         12. Subject is medically able to undergo the study procedures and physically able to
             adhere to the visit schedule at the time of study entry.

         13. For women of child bearing capacity, negative pregnancy test during the Screening
             Period and at the Pre-Operative Visit.

         14. Males and females will agree to practice effective birth control during study
             participation and up to one year after.

        Exclusion Criteria:

          1. Subject with causes of weakness, sensory loss and/or autonomic dysfunction other than
             TM have not been practically excluded.

          2. Subject with significant cognitive impairment, clinical dementia, or major psychiatric
             illness including psychosis, bipolar disease, major depression, as determined by the
             DSM-V.

          3. Subject with a diagnosis of a neurodegenerative disease (e.g., ALS, Parkinson's
             disease, Alzheimer's disease).

          4. Subject suffering with medical conditions that impair nerve or muscle function (e.g.,
             notable peripheral neuropathy, metabolic muscle disease) or any disease or condition
             that would impair the subject's neuromuscular function or impair the adequate
             assessment of the subject's function (e.g., severe osteoarthritis).

          5. Subject with a clinically significant history of unstable cardiac, pulmonary, renal,
             hepatic, endocrine, hematologic, or active malignancy or infectious disease or other
             medically significant illness that may render them at an unacceptable risk for surgery
             or that may cause them to be unable to complete the scheduled duration of the trial.

          6. History of spine surgery or anatomic variation incompatible with route of
             administration (as determined by neurosurgeon).

          7. Severe spinal stenosis or cord compression causing myelopathy.

          8. Abnormal flow voids on the surface of the spinal cord suggestive of arteriovenous
             malformation (AVM) or evidence of a vascular cause of a myelopathy (e.g., infarct of
             spinal artery).

          9. Any evidence of CNS malignancy or clinically significant CNS lesions as defined by
             imaging studies of the CNS (MRI of brain and spinal cord).

         10. Uncontrolled hypertension (Systolic BP>180mmHg and/or Diastolic BP >110mmHg).

         11. Any history of thrombotic or embolic events.

         12. Any poorly controlled medical conditions that, in the opinion of the site investigator
             and/or surgeon, increase risk of surgery to a medically unacceptable degree.

         13. Subjects who cannot undergo MRI examination because of any contraindication to the
             procedure, including the presence of a pacemaker, an implanted defibrillator or
             certain other implanted electronic or metallic devices, or who have been or might have
             been exposed to metal fragments, or any reason the subject cannot undergo an MRI
             routinely for the duration of the trial.

         14. Subject with clinically significant abnormal clinical laboratory values, as determined
             by the Investigator at the screening visit (Visit 1).

         15. Subject who is immune compromised (by therapeutic agent or disease) or who has a
             condition contraindicated to treatment with immunosuppression agents (e.g.,
             tuberculosis, latent infection) as determined by history or testing. Any subject with
             an ongoing infection until it has been adequately treated and it is deemed to be
             resolved.

         16. Subject with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value
             >3.0 times the upper limit of normal at the screening visit (Visit 1).

         17. Subject with diabetes or HgbA1c > 6.5

         18. Subject with a history of alcohol or drug abuse or dependence within 1 year of
             screening visit (Visit 1), per DSM-V criteria.

         19. Subject unlikely to comply with study requirements, as determined by Investigator.

         20. Subject who has been exposed to any other experimental agent (off-label use or
             investigational) within 60 days of screening visit (Visit 1). Biologic agents may need
             additional time for washout and will be evaluated by the Sponsor on a case-by-case
             basis.

         21. Subject with pre-existing anti-human leukocyte antigen (HLA) class I or class II
             antibodies directed against the Q-Cells®, as determined by panel reactive antibody
             (PRA) assay.

         22. Allergy to study treatment or any of its constituents (e.g., chicken eggs), or allergy
             to any of the co-administered immunosuppressants or any of their excipients.

         23. Subject with any medical condition or using concomitant medication that would
             contraindicate the use of tacrolimus, mycophenolate mofetil, or prednisone as
             determined by Investigator.

         24. Subject has undergone stem cell transplantation (including T-cell or bone marrow
             transplants) at any time prior to study (within or outside the US).

         25. Subject with evidence of deep vein thrombosis (DVT) by venous ultrasound or any
             previous evidence of DVT.

         26. Subject has recent (1 year) or recurrent history of gastrointestinal bleeding or
             peptic ulcer disease or is under active treatment to prevent recurrence.

         27. Subject with estimated glomerular filtration rate at screening of less than 60
             mL/min/1.73m2.

         28. Subjects with hereditary deficiency of hypoxanthine-guanine phosphoribosyl-transferase
             (HGPRT) such as Lesch-Nyhan and Kelley-Seegmiller syndrome.

         29. Vaccination with live virus within 6 weeks of screening.

         30. History or evidence of optic neuritis.

         31. Any reason, in the judgment of the investigator, which would make the subject
             inappropriate for entry into this trial.
      

Gender

All

Ages

18 Years - 70 Years

Accepts Healthy Volunteers

No

Contacts

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Administrative Informations


NCT ID

NCT03887273

Organization ID

QTM-101


Responsible Party

Sponsor

Study Sponsor

Q Therapeutics, Inc.


Study Sponsor

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Verification Date

November 2020