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Early versus rescue plasma exchange for severe optic neuritis and transverse myelitis

A Randomized Controlled, Open-Label, Rater-Blinded Pragmatic Trial, Treatment of Inflammatory Myelitis and Optic Neuritis With Early vs Rescue Plasma Exchange (TIMELY-PLEX)

Phase 3 Interventional Mayo Clinic · NCT07100990

This trial will see if starting plasma exchange early versus using it only as a rescue after high-dose steroids improves vision for adults with severe optic neuritis and improves neurologic recovery for adults with severe transverse myelitis.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment382 (estimated)
Ages18 Years and up
SexAll
SponsorMayo Clinic Academic / other
Drugs / interventionstocilizumab, satralizumab, eculizumab, ravulizumab, rituximab, ocrelizumab, ofatumumab, ublituximab, inebilizumab, alemtuzumab, radiation, methotrexate, cyclophosphamide
Locations31 sites (Scottsdale, Arizona and 30 other locations)
Trial IDNCT07100990 on ClinicalTrials.gov

What this trial studies

This Phase 3 randomized trial enrolls adults with severe optic neuritis or severe transverse myelitis into two parallel sub-trials comparing high-dose corticosteroids alone versus high-dose corticosteroids plus early therapeutic plasma exchange (PLEX) or rescue PLEX after steroid therapy. Optic neuritis participants must have new MRI evidence and visual acuity 20/200 or worse within 8 days of symptom onset, and early PLEX must be able to start within 72 hours of the first steroid dose for those randomized to that arm. The primary outcomes are visual recovery in the optic neuritis sub-trial and neurological disability in the transverse myelitis sub-trial, measured over prespecified follow-up. The trial is sponsored by Mayo Clinic with PCORI collaboration and will enroll at academic centers in Arizona, California, and Colorado.

Who should consider this trial

Good fit: Adults (≥18) presenting within the acute enrollment windows with new severe optic neuritis (MRI-confirmed and visual acuity ≤20/200) or severe transverse myelitis without prior episode who can access participating sites and receive PLEX within required timeframes are ideal candidates.

Not a fit: Patients with milder disease, chronic or recurrent optic neuritis, significant ophthalmologic comorbidities, or those unable to present within the required acute window or to receive timely PLEX are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, earlier use of PLEX could lead to faster and greater recovery of vision in optic neuritis and reduced long-term neurological disability in transverse myelitis.

How similar studies have performed: Plasma exchange is an established rescue therapy for steroid-refractory demyelinating optic neuritis and myelitis, but randomized phase 3 evidence comparing early versus rescue PLEX is limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
Study Population and Setting

The proposal will recruit participants presenting to participating sites with severe ON or severe TM to two separate sub-trials. The detailed inclusion and exclusion criteria for each sub-trial are listed below:

Optic Neuritis Sub-Trial:

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)

Where this trial is running

Scottsdale, Arizona and 30 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Optic NeuritisMyelitisMyelitis, TransversePlasma ExchangePlasmapheresisApheresisPheresis
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.