A Randomized Controlled, Open-Label, Rater-Blinded Pragmatic Trial, Treatment of Inflammatory Myelitis and Optic Neuritis With Early Vs Rescue Plasma Exchange (Timely-Plex)
Early vs Rescue Plasma Exchange in Severe Optic Neuritis and Transverse Myelitis
Devon Mackay
Primary Investigator
Brief description of study
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.
Detailed description of study
High contrast visual acuity [Time Frame: 6 months] The Optic Neuritis subjects will have high contrast visual acuity measured by ETDRS 100% high-contrast Sloan letter charts. A high contrast visual acuity of 20/20 is considered "normal," a high contrast visual acuity of 20/40 or better is required to be able to drive without restrictions, and a high contrast visual acuity of 20/200 or worse is considered legally blind. Expanded Disability Status Score (EDSS) [Time Frame: 6 months] The level of disability in Transverse Myelitis subjects will be assessed using the Expanded Disability Status Scale (EDSS). The EDSS assesses various neurological functional systems, including pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, and cerebral functions and ranges from 0 (normal neurological examination) to 10 (death). Higher scores indicate greater disability. Visual and cerebral functional system scores will be excluded from the EDSS calculation for quantification of Transverse Myelitis-related disability.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Myelitis, Optic Neuritis
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Age: 18 years - 100 years
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Gender: All
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)
This study investigates the effects of early versus rescue Therapeutic Plasma Exchange (PLEX) on visual and neurological outcomes in people with severe Optic Neuritis and Transverse Myelitis. Optic Neuritis is a condition where the optic nerve, which connects the eye to the brain, becomes inflamed, leading to vision loss. Transverse Myelitis is when the spinal cord becomes inflamed, affecting movement and sensation. The study aims to see if starting PLEX early can improve vision and reduce disability.
Participants will undergo a procedure called Therapeutic Plasma Exchange (PLEX), where blood is filtered to remove harmful substances. High contrast visual acuity will be measured for Optic Neuritis using special charts to assess vision clarity. For Transverse Myelitis, the Expanded Disability Status Scale (EDSS) will be used to evaluate the level of disability, focusing on various neurological functions.
- Who can participate: Adults aged 18 and older with severe Optic Neuritis or Transverse Myelitis may participate. Key eligibility includes new optic nerve inflammation, poor visual acuity, and ability to start PLEX within specific timeframes. Exclusions include prior optic neuritis in the affected eye and certain medical conditions or treatments.
- Study details: Participants will receive Therapeutic Plasma Exchange (PLEX) treatment, which involves filtering the blood to remove harmful substances. The study will compare early versus delayed PLEX treatment. Participants must follow study procedures and be available for the study duration.
- Study timelines: The study will last 6 months.
