Treatment of Inflammatory Myelitis and Optic Neuritis With Early vs Rescue Plasma Exchange (TIMELY-PLEX)
Purpose
The purpose of this research is to evaluate if early vs rescue Therapeutic Plasma Exchange (PLEX) treatment algorithm leads to better visual outcomes in severe Optic Neuritis and leads to better neurological disability outcomes in severe Transverse Myelitis.
Conditions
- Optic Neuritis
- Myelitis
- Myelitis, Transverse
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- ≥18 years of age - MRI orbits demonstrating evidence of new T2 hyperintensity and/or post-gadolinium contrast enhancement of the optic nerve(s) and meeting the clinical criteria for Optic Neuritis - Visual acuity 20/200 or worse - Within 8 days of onset of visual symptoms - Able to initiate PLEX within 72h of the first dose of HDCS (if randomized to the "Early PLEX" treatment arm) - Able to sign and date informed consent form - Willingness to comply with all study procedures and availability for the duration of the study
Exclusion Criteria
- Evidence of prior episode of optic neuritis in the affected eye (by history or ophthalmological evaluation) - Ophthalmological comorbidity that would significantly affect best corrected visual acuity or visual fields - Pregnancy - Presence of any contraindication to receiving HDCS or PLEX, including, but not limited to, hemodynamic instability, significant bleeding/coagulopathy, or sepsis. - Any medical condition that, in the opinion of the investigator, may interfere with the patient's participation in the trial, pose any added risk for the patient, or confound the assessment of the patient (including but not limited to concurrent neurological disease and/or medical comorbidity) - Treatment with any investigational agent within 6 months of baseline or five half-lives of the investigational agent (whichever is longer) - Ongoing/prior treatment with immune-modulating/immunosuppressive therapy including: - Mycophenolate mofetil, azathioprine, methotrexate, fingolimod, siponimod, ponesimod, ozanimod, tocilizumab, satralizumab, eculizumab or ravulizumab within 3 months of randomization - Anti-CD20 (rituximab, ocrelizumab, ofatumumab, ublituximab) or anti-CD19 (inebilizumab) therapy within 6 months of randomization - Intravenous or subcutaneous immune globulin within 3 months of randomization - Plasma exchange within 3 months of randomization - Interferon-beta, glatiramer acetate, fumarates (dimethyl fumarate, monomethyl fumarate, diroximel fumarate) within 1 month of randomization - Teriflunomide use within prior 24 months - Systemic corticosteroid therapy (intravenous or oral; excluding inhaled or topical corticosteroids) within 1 month of randomization - Any previous treatment with alemtuzumab, cladribine, mitoxantrone or cyclophosphamide - Previous treatment with any immune-modulating or immunosuppressive therapy not mentioned above within 6 months of randomization or five-half-lives (whichever is longer) Transverse Myelitis Sub-Trial: Inclusion criteria: - ≥18 years of age - Diagnosis of Transverse Myelitis (defined based on modified criteria adapted from the 2002 Transverse Myelitis Consortium Working Group; ALL are required) - Development of sensory, motor and/or autonomic symptomatology attributable to spinal cord dysfunction - Onset of symptoms to nadir >12 hours - Exclusion of extra-axial compressive etiology by neuroimaging - Demonstration of inflammation within the spinal cord by presence of intramedullary T2 lesion (post-gadolinium enhancing OR non-enhancing) on MRI - Expanded Disability Status Scale [EDSS] ≥3.0 (excluding visual and cerebral functional systems) - EDSS Pyramidal Functional System Score ≥ 2 - Within 8 days of onset of motor symptoms - Able to initiate PLEX within 48h of the first dose of HDCS (if randomized to the "Early PLEX" treatment arm) - Able to sign and date informed consent form - Willingness to comply with all study procedures and availability for the duration of the study Exclusion criteria: - Pre-existing ambulatory, motor, sensory, or bowel/bladder disability of any cause that could confound trial assessments - Fulfillment of possible, probable or definite spinal cord infarction diagnosis per proposed diagnostic criteria (Zalewski et al. JAMA Neurology 2018) - History of radiation to the spine - Pregnancy - High clinical suspicion for infectious etiology of myelitis (e.g., fever, rash or other findings) - Presence of any contraindication to receiving HDCS or PLEX, including, but not limited to, hemodynamic instability, significant bleeding/coagulopathy, or sepsis. - Any medical condition that, in the opinion of the investigator, may interfere with the patient's participation in the trial, pose any added risk for the patient, or confound the assessment of the patient (including but not limited to concurrent neurological disease and/or medical comorbidity) - Treatment with any investigational agent within 24 weeks of baseline or five half-lives of the investigational agent (whichever is longer) - Ongoing/prior treatment with immune-modulating/immunosuppressive therapy including: Mycophenolate mofetil, azathioprine, methotrexate, fingolimod, siponimod, ponesimod, ozanimod, tocilizumab, satralizumab, eculizumab or ravulizumab within 3 months of randomization - Anti-CD20 (rituximab, ocrelizumab, ofatumumab, ublituximab) or anti-CD19 (inebilizumab) therapy within 6 months of randomization - Intravenous or subcutaneous immune globulin within 3 months of randomization - Plasma exchange within 3 months of randomization - Interferon-beta, glatiramer acetate, fumarates (dimethyl fumarate, monomethyl fumarate, diroximel fumarate) within 1 month of randomization - Teriflunomide use within prior 24 months - Systemic corticosteroid therapy (intravenous or oral; excluding inhaled or topical corticosteroids) within 1 month of randomization - Any previous treatment with alemtuzumab, cladribine, mitoxantrone or cyclophosphamide - Previous treatment with any immune-modulating or immunosuppressive therapy not mentioned above within 6 months of randomization or five-half-lives (whichever is longer)
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Optic Neuritis (ON) "Rescue PLEX" |
Adult participants presenting within 8 days of symptom onset with severe Optic Neuritis (ON) (visual acuity of 20/200 or worse |
|
|
Experimental Optic Neuritis (ON) "Early PLEX" |
Adult participants presenting within 8 days of symptom onset with severe Optic Neuritis (ON) (visual acuity of 20/200 or worse |
|
|
Active Comparator Transverse Myelitis "Rescue PLEX" |
Adult participants presenting within 8 days of symptom onset with severe Transverse Myelitis (TM) (expanded Disability Status Scale [EDSS] of 3.0 or worse) |
|
|
Experimental Transverse Myelitis "Early PLEX" |
Adult participants presenting within 8 days of symptom onset with severe Transverse Myelitis (TM) (expanded Disability Status Scale [EDSS] of 3.0 or worse) |
|
Recruiting Locations
Mayo Clinic Arizona
Scottsdale, Arizona 85259
Scottsdale, Arizona 85259
University of California, Davis
Sacramento, California 95817
Sacramento, California 95817
University of Colorado - Anschutz Medical
Aurora, Colorado 80045
Aurora, Colorado 80045
Yale University School of Medicine
North Haven, Connecticut 06510
North Haven, Connecticut 06510
Mayo Clinic Florida
Jacksonville, Florida 32224
Jacksonville, Florida 32224
University of Illinois Chicago
Chicago, Illinois 60612
Chicago, Illinois 60612
Northwestern University
Evanston, Illinois 60208
Evanston, Illinois 60208
Indiana University
Indianapolis, Indiana 46202
Indianapolis, Indiana 46202
University of Maryland, Baltimore
Baltimore, Maryland 21201
Baltimore, Maryland 21201
Johns Hopkins University
Baltimore, Maryland 21218
Baltimore, Maryland 21218
Medstar Health Research Institute
Columbia, Maryland 21044
Columbia, Maryland 21044
Harvard University Massachusetts General Hospital
Boston, Massachusetts 02114
Boston, Massachusetts 02114
Boston Medical Center
Boston, Massachusetts 02118
Boston, Massachusetts 02118
Regents of the University of Michigan
Ann Arbor, Michigan 48105
Ann Arbor, Michigan 48105
Mayo Clinic in Rochester
Rochester, Minnesota 55905
Rochester, Minnesota 55905
University of Mississippi Medical Center
Jackson, Mississippi 39216
Jackson, Mississippi 39216
Icahn School of Medicine at Mount Sinai
New York, New York 10029
New York, New York 10029
Columbia University
New York, New York 10032
New York, New York 10032
Weill Cornell Medical College
New York, New York 10065
New York, New York 10065
Duke University Health System
Durham, North Carolina 27710
Durham, North Carolina 27710
University Hospitals Cleveland Medical Center
Cleveland, Ohio 44106
Cleveland, Ohio 44106
Oregon Health & Sciences University
Portland, Oregon 97239
Portland, Oregon 97239
University of Pittsburgh Medical Center, Magee Hospital
Pittsburgh, Pennsylvania 15213
Pittsburgh, Pennsylvania 15213
Vanderbilt University Medical Center
Nashville, Tennessee 37232
Nashville, Tennessee 37232
UT Southwestern Medical Center
Dallas, Texas 75390
Dallas, Texas 75390
University of Utah
Salt Lake City, Utah 84112
Salt Lake City, Utah 84112
University of Virginia
Charlottesville, Virginia 22908
Charlottesville, Virginia 22908
University of Washington
Seattle, Washington 98195
Seattle, Washington 98195
More Details
- Status
- Recruiting
- Sponsor
- Mayo Clinic