Optic NeuritisPhase 3TIMELY-PLEXNCT07100990
Treatment of Inflammatory Myelitis and Optic Neuritis With Early vs Rescue Plasma Exchange (TIMELY-PLEX)
A Phase 3 study testing High-dose corticosteroids (HDCS) and High-dose corticosteroids (HDCS) and PLEX in people with Optic Neuritis and Myelitis, run by Mayo Clinic at 35 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Optic Neuritis, Myelitis, Myelitis, Transverse
- What is being tested?
- High-dose corticosteroids (HDCS) and High-dose corticosteroids (HDCS) and PLEX
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 382 participants
- Where
- 35 sitesUnited States
- Study dates
- 11 Jul 2025to 30 Apr 2031
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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 14 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
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- Willingness to comply with all study procedures and availability for the duration of the study
- ≥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 14 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
Who cannot join
- 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)
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- 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:
- 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)
Trial locations and contacts
35 sites in 1 country. Contact the study team or a site near you to ask about taking part.
35 sites in 1 country
United States35 sites, 32 recruiting
- Recruiting
Regents of the University of Michigan
Ann Arbor, Michigan, 48105
Lindsey Delott, MD, 734-764-5106, ldelott@med.umich.edu
Clare McKolay, 734-998-1962, delottlab@umich.edu
- Recruiting
University of Colorado - Anschutz Medical
Aurora, Colorado, 80045
Jeffrey Bennett, MD, PhD, 303-724-0090, jeffrey.bennett@cuanschutz.edu
Jordan Hood, 303-724-6104, jordan.j.hood@cuanschutz.edu
- Recruiting
University of Maryland, Baltimore
Baltimore, Maryland, 21201
Sarah Fredrich, MD, 410-328-1885, sfredrich@som.umaryland.edu
Kerry Naunton, 410-328-1885, knaunton@som.umaryland.edu
- Recruiting
Johns Hopkins University
Baltimore, Maryland, 21218
Elias Sotirchos, MD, (410) 550-5624, ess@jhmi.edu
Lauren Stelmash, lstelma2@jhmi.edu
- Active, not recruiting
University of Alabama at Birmingham
Birmingham, Alabama, 35205
- Recruiting
Harvard University Massachusetts General Hospital
Boston, Massachusetts, 02114
Anastasia Vishnevetsky, MD, MPH, 203-430-9425, avishnevetsky@mgb.org
Anastasia Vishnevetsky, MD, MPH
- Recruiting
Boston Medical Center
Boston, Massachusetts, 02118
Crandall Peeler, MD, 603-667-0962, Crandall.peeler@bmc.org
Sreevardhan Alluri, 617-414-8848, sreevardhan.alluri@bmc.org
- Recruiting
University of North Carolina School of Medicine
Chapel Hill, North Carolina, 27599
Irena Dujmovic Basuroski, MD, PhD, 919-945-4752, irdujm@neurology.unc.edu
Jackie Koble, koblej@neurology.unc.edu
- Recruiting
University of Virginia
Charlottesville, Virginia, 22908
Alexandra Simpson, MD, 281-726-8081, zsk3ne@uvahealth.org
Matt Baron, 434-297-4102, ukx3sv@uvahealth.org
- Recruiting
University of Illinois Chicago
Chicago, Illinois, 60612
Peter MacIntosh, MD, 312-996-9120, pmacint1@uic.edu
Bhavana Kolli, 312-355-6488, bkolli2@uic.edu
- Recruiting
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Hesham Abboud, MD, 216-844-5137, hesham.abboud@uhhospitals.org
Stacy Pot, BA, 216-844-5605, stacy.pot@uhhospitals.org
- Recruiting
Medstar Health Research Institute
Columbia, Maryland, 21044
Benjamin Osborne, MD, 240-701-6250, bjo102@gunet.georgetown.edu
Helen Girma, 202-912-1308, helen.girma@medstar.net
- Recruiting
UT Southwestern Medical Center
Dallas, Texas, 75390
Peter Sguigna, MD, 214-645-0286, Peter.Sguigna@UTSouthwestern.edu
Taylor Hinojo, MS, 214-645-3230, Taylor.Hinojo@UTSouthwestern.edu
- Recruiting
Duke University Health System
Durham, North Carolina, 27710
Nathan Tagg, MD, 240-401-2631, nathan.tagg@duke.edu
Sarah Jones, 919-681-6584, sarah.jones1@duke.edu
- Recruiting
Northwestern University
Evanston, Illinois, 60208
Shailee Shah, MD, 847-491-3741, shailee.shah@northwestern.edu
Justin Hill, 312-503-5184, justin.hill@northwestern.edu
- Recruiting
Indiana University
Indianapolis, Indiana, 46202
Devin Mackay, MD, 317-948-5450, ddmackay@iu.edu
Amy Perkins, 317-278-4214, ajperk@iu.edu
- Recruiting
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Melanie Truong-Le, DO, OD, 601-984-2040, mtruongle@umc.edu
Marcus T Wells, MS, 601-984-5046, MWells4@UMC.EDU
- Recruiting
Mayo Clinic Florida
Jacksonville, Florida, 32224
Eric Eggenberger, DO, 904-953-2232, eggenberger.eric@mayo.edu
Eric Eggenberger, DO
- Active, not recruiting
Loma Linda University
Loma Linda, California, 92350
- Recruiting
University of Miami
Miami, Florida, 33136
Byron Lam, MD, 305-326-6021, blam@med.miami.edu
Adriana Drada, apd86@med.miami.edu
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Reid Longmuir, MD, 615-936-2020, reid.longmuir@vumc.org
Hani Rashed, 615-875-8670, hani.rashed@vumc.org
- Recruiting
NYU Langone Health
New York, New York, 10016
Scott Grossman, MD, 212-263-7744, Scott.Grossman@nyulangone.org
Christina Marini, MPH, 929-455-5622, Christina.Marini@nyulangone.org
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Sammita Satyanarayan, MD, 212-241-6854, sammita.satyanarayan@mssm.edu
Susan Filomena, 212-241-3841, susan.e.filomena@mssm.edu
- Recruiting
Columbia University
New York, New York, 10032
Kiran Kiran, MD, 734-717-2160, ktt2115@cumc.columbia.edu
Gerome Vallejos, 619-882-6469, gbv2110@cumc.columbia.edu
- Recruiting
Weill Cornell Medical College
New York, New York, 10065
Marc Dinkin, MD, 646-962-2020, mjd2004@med.cornell.edu
Jaffer Shah, 516-749-0058, jas4041@med.cornell.edu
- Recruiting
Yale University School of Medicine
North Haven, Connecticut, 06510
Annalisa Morgan, MD, 203-287-6100, Annalisa.morgan@yale.edu
Dimitri Duvilaire, 203-907-5399, dimitri.duvilaire@yale.edu
- Recruiting
Dean McGee Eye Institute at University of Oklahoma Health Sciences
Oklahoma City, Oklahoma, 73117
Andrew Melson, MD, 405-271-6307, Andrew-melson@ou.edu
Crystal McAfee, 405-271-6307, crystal-mcafee@dmei.org
- Active, not recruiting
Wills Eye Hospital
Philadelphia, Pennsylvania, 19103
- Recruiting
University of Pittsburgh Medical Center, Magee Hospital
Pittsburgh, Pennsylvania, 15213
Ingrid Loma-Miller, MD, 412-641-6600, lomamilleri@upmc.edu
Courtney Skasik, 717-395-2614, skasikca@upmc.edu
- Recruiting
Oregon Health & Sciences University
Portland, Oregon, 97239
Elizabeth Silbermann, MD, 515-991-4457, silberme@ohsu.edu
Jamie Anderson, 503-494-1986, ajamie@ohsu.edu
- Recruiting
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
John Chen, MD, PhD, 507-284-4946, chen.john@mayo.edu
Jessica Morgan, 507-293-9689, morgan.jessica@mayo.edu
- Recruiting
University of California, Davis
Sacramento, California, 95817
Yin A Liu, MD, PhD, 916-734-6602, aycliu@health.ucdavis.edu
Denise C Macias, 916-734-6303, dcmacias@health.ucdavis.edu
- Recruiting
University of Utah
Salt Lake City, Utah, 84112
Stacey Clardy, MD, 801-585-7575, stacey.clardy@hsc.utah.edu
Trieste Francis, 801-587-3864, Trieste.Francis@hsc.utah.edu
- Recruiting
Mayo Clinic Arizona
Scottsdale, Arizona, 85259
Dean Wingerchuk, MD, 480-684-3127, wingerchuk.dean@mayo.edu
Dean Wingerchuk, MD
- Recruiting
University of Washington
Seattle, Washington, 98195
Yujie Wang, MD, 832-628-3220, yujie@uw.edu
Courtney Francis, francis3@uw.edu
About this study
Official title: A Randomized Controlled, Open-Label, Rater-Blinded Pragmatic Trial, Treatment of Inflammatory Myelitis and Optic Neuritis With Early vs Rescue Plasma Exchange (TIMELY-PLEX)
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
- Being tested
- High-dose corticosteroids (HDCS), High-dose corticosteroids (HDCS) and PLEX
- Keywords
- Plasma Exchange, Plasmapheresis, Apheresis, Pheresis
- Medical subject headings
- Optic Neuritis, Myelitis, Myelitis, Transverse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High-dose corticosteroids (HDCS)Drug
Also called Rescue Plex
Subjects will receive initial treatment with high-dose corticosteroids (HDCS) in the form of methylprednisolone (1,000mg daily) administered intravenously for 5 days or a bioequivalent dose of oral corticosteroids (e.g., 1,250mg prednisone daily or 176mg dexamethasone daily).
Subjects will be escalated to PLEX if there is an insufficient response to HDCS (decision point at 14±2 days for the ON sub-trial and 7±1 days for the TM sub-trial) PLEX will be performed as 5 sessions over 5-10 days, with 1-1.5 plasma volumes exchanged per session.
High-dose corticosteroids (HDCS) and PLEXDrug
Also called Early Plex
Subjects will receive treatment with high-dose corticosteroids (HDCS) and PLEX initiated concurrently.
HDCS will be administered in the form of methylprednisolone (1,000mg daily) administered intravenously for 5 days or a bioequivalent dose of oral corticosteroids (e.g., 1,250mg prednisone daily or 176mg dexamethasone daily).
PLEX will be performed as 5 sessions over 5-10 days, with 1-1.5 plasma volumes exchanged per session.
| Study group | Role | What they receive |
|---|---|---|
| Optic Neuritis (ON) "Rescue PLEX" | Active comparator | Adult participants presenting within 14 days of symptom onset with severe Optic Neuritis (ON) (visual acuity of 20/200 or worse Receives: Drug: High-dose corticosteroids (HDCS) |
| Optic Neuritis (ON) "Early PLEX" | Experimental | Adult participants presenting within 14 days of symptom onset with severe Optic Neuritis (ON) (visual acuity of 20/200 or worse Receives: Drug: High-dose corticosteroids (HDCS) and PLEX |
| Transverse Myelitis "Rescue PLEX" | Active comparator | Adult participants presenting within 14 days of symptom onset with severe Transverse Myelitis (TM) (expanded Disability Status Scale [EDSS] of 3.0 or worse) Receives: Drug: High-dose corticosteroids (HDCS) |
| Transverse Myelitis "Early PLEX" | Experimental | Adult participants presenting within 14 days of symptom onset with severe Transverse Myelitis (TM) (expanded Disability Status Scale [EDSS] of 3.0 or worse) Receives: Drug: High-dose corticosteroids (HDCS) and PLEX |
What is being measured
The primary outcome is the main question the study is designed to answer.
High contrast visual acuity
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.
Measured: 6 months
Expanded Disability Status Score (EDSS)
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 cereberal 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.
Measured: 6 months
Secondary outcomes (11)
Low contrast (2.5%) visual acuity
Optic Neuritis subjects will have low contrast visual acuity (best corrected) assessed with 2.5% low-contrast Sloan letter charts
Measured: 6 months
Peri-papillary retinal nerve fiber layer (RNFL thickness)
Optic Neuritis subjects will have RNFL thickness measured via Retinal Optical Coherence Tomography (OCT).
Measured: 6 months
Macular ganglion cell-inner plexiform layer (GCIPL) thicknesses
Optic Neuritis subjects will have GCIPL thickness measured via Retinal Optical Coherence Tomography (OCT).
Measured: 6 months
Hardy Rand and Rittler (HRR) color plates
The Hardy-Rand-Rittler (HRR) color plates test will be administered to Optic Neuritis subjects. The HRR is scored based on the number of correct responses to the diagnostic plates, with the total number of correct figures out of 28 being the primary score.
Measured: 6 months
National Eye Institute (NEI) 10-Item Neuro-Ophthalmic Supplement
Optic Neuritis subjects will complete the 10-Item Neuro-Ophthalmic Supplement, a 10-item questionnaire used to assess visual dysfunction in patients with neuro-ophthalmologic disorders. It is scored on a scale of 0 to 100, with higher scores indicating better visual functioning.
Measured: 6 months
Ambulatory disability
Transverse Myelitis subjects will be assessed for ambulatory disability using the Hauser Ambulation Index, a timed 25 foot, 6 minute walk.
Measured: 6 months
Manual dexterity (Nine-Hole Peg Test)
The Nine-Hole Peg Test will be administered to the Transverse Myelitis subjects. Subjects will be asked to take the pegs from a container, one by one, and place them into holes on the board as quickly as possible. They will then remove the pegs, one by one, from the board as quickly as possible. Scores are based on the time taken to complete the activity and are reported in seconds.
Measured: 6 months
Patient Determined Disease Steps (PDDS)
Transverse Myelitis subjects will complete the Patient-Determined Disease Steps (PDDS), a self-reported disability scale with 9 levels ranging from no disability to bedridden.
Measured: 6 months
Spinal Cord Injury Quality of Life questionnaire (SCI-QoL)
Transverse Myelitis subjects will complete the The Spinal Cord Injury Quality of Life questionnaire (SCI-QoL), which includes assessments of specific domains related to bladder/bowel dysfunction, pain, pressure ulcers, mobility/ambulation, fine motor skills, self-care, and wheelchair mobility.
Measured: 6 months
PLEX Complications
Total number of adverse events categorized according to the Common Terminology Criteria for Adverse Events v5.0
Measured: 2 weeks, 1 month
National Eye Institute (NEI) Visual Function Questionnaire (VFQ)-25
Optic Neuritis subjects will complete the National Eye Institute Visual Functioning Questionnaire-25. The questionnaire consists of 25 items, covering 11 vision-related domains, plus a single global-rating item. Items are scored and converted to a 0- to 100-point scale where higher scores indicate better functioning.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2025
- Study start11 Jul 2025
- Primary completion1 Apr 2029 (estimated)
- Study completion30 Apr 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Optic NeuritisStudies of the same condition, open and under way.
- More trials run by Mayo ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 382 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Patient-Centered Outcomes Research Institute
- Responsible party
- Principal investigator, John J Chen, Mayo Clinic
- Investigators
- John Chen, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07100990
- Sponsor's protocol ID
- 25-000657
- Acronym
- TIMELY-PLEX
- Status last verified
- Jul 2026
- First submitted
- 28 Jul 2025
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No