Recruiting

Phase 3

PLEX vs. PLEXTreatment of Inflammatory Myelitis and Optic Neuritis With Early vs Rescue Plasma Exchange (TIMELY-PLEX)

Sponsor:

Mayo Clinic

Code:

NCT07100990

Conditions

Optic Neuritis

Myelitis

Myelitis, Transverse

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

High-dose corticosteroids (HDCS)

High-dose corticosteroids (HDCS) and PLEX

Study Details

Brief 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.

Conditions

Optic Neuritis

Myelitis

Myelitis, Transverse

Study ID

NCT07100990

Start date

Jul 11, 2025

Status verified date

Jul, 2026

Completion date

Apr 30, 2031

Anticipated

Primary completion date

Apr 1, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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)

Study Design

Enrollment

382 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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)

Interventions

High-dose corticosteroids (HDCS)

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±2 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 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.

Primary outcome measure

High contrast visual acuity [ Time Frame: 6 months ]
Expanded Disability Status Score (EDSS) [ Time Frame: 6 months ]

Central Contacts and Locations

Locations

Mayo Clinic Arizona

Recruiting

Scottsdale, Arizona, United States, 85259

Contacts

Dean Wingerchuk, MD

480-684-3127 wingerchuk.dean@mayo.edu

Principal Investigator:

Dean Wingerchuk, MD

University of California, Davis

Recruiting

Sacramento, California, United States, 95817

Contacts

Yin A Liu, MD, PhD

916-734-6602 aycliu@health.ucdavis.edu

Denise C Macias

916-734-6303 dcmacias@health.ucdavis.edu

Principal Investigator:

Yin A Liu, MD, PhD

University of Colorado - Anschutz Medical

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Jeffrey Bennett, MD, PhD

303-724-0090 jeffrey.bennett@cuanschutz.edu

Jordan Hood

303-724-6104 jordan.j.hood@cuanschutz.edu

Principal Investigator:

Jeffrey Bennett, MD, PhD

Yale University School of Medicine

Recruiting

North Haven, Connecticut, United States, 06510

Contacts

Annalisa Morgan, MD

203-287-6100 Annalisa.morgan@yale.edu

Dimitri Duvilaire

203-907-5399 dimitri.duvilaire@yale.edu

Principal Investigator:

Annalisa Morgan, MD

Mayo Clinic Florida

Recruiting

Jacksonville, Florida, United States, 32224

Contacts

Eric Eggenberger, DO

904-953-2232 eggenberger.eric@mayo.edu

Principal Investigator:

Eric Eggenberger, DO

University of Miami

Recruiting

Miami, Florida, United States, 33136

Contacts

Byron Lam, MD

305-326-6021 blam@med.miami.edu

Adriana Drada

apd86@med.miami.edu

Principal Investigator:

Byron Lam, MD

University of Illinois Chicago

Recruiting

Chicago, Illinois, United States, 60612

Contacts

Peter MacIntosh, MD

312-996-9120 pmacint1@uic.edu

Bhavana Kolli

312-355-6488 bkolli2@uic.edu

Principal Investigator:

Peter MacIntosh, MD

Northwestern University

Recruiting

Evanston, Illinois, United States, 60208

Contacts

Shailee Shah, MD

847-491-3741 shailee.shah@northwestern.edu

Justin Hill

312-503-5184 justin.hill@northwestern.edu

Principal Investigator:

Shailee Shah, MD

Indiana University

Recruiting

Indianapolis, Indiana, United States, 46202

Contacts

Devin Mackay, MD

317-948-5450 ddmackay@iu.edu

Amy Perkins

317-278-4214 ajperk@iu.edu

Principal Investigator:

Devin Mackay, MD

University of Maryland, Baltimore

Recruiting

Baltimore, Maryland, United States, 21201

Contacts

Sarah Fredrich, MD

410-328-1885 sfredrich@som.umaryland.edu

Kerry Naunton

410-328-1885 knaunton@som.umaryland.edu

Principal Investigator:

Sarah Fredrich, MD

Johns Hopkins University

Recruiting

Baltimore, Maryland, United States, 21218

Contacts

Elias Sotirchos, MD

(410) 550-5624 ess@jhmi.edu

Lauren Stelmash

lstelma2@jhmi.edu

Principal Investigator:

Elias Sotirchos, MD

Medstar Health Research Institute

Recruiting

Columbia, Maryland, United States, 21044

Contacts

Benjamin Osborne, MD

240-701-6250 bjo102@gunet.georgetown.edu

Helen Girma

202-912-1308 helen.girma@medstar.net

Principal Investigator:

Benjamin Osborne, MD

Harvard University Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

Anastasia Vishnevetsky, MD, MPH

203-430-9425 avishnevetsky@mgb.org

Principal Investigator:

Anastasia Vishnevetsky, MD, MPH

Boston Medical Center

Recruiting

Boston, Massachusetts, United States, 02118

Contacts

Crandall Peeler, MD

603-667-0962 Crandall.peeler@bmc.org

Sreevardhan Alluri

617-414-8848 sreevardhan.alluri@bmc.org

Principal Investigator:

Crandall Peeler, MD

Regents of the University of Michigan

Recruiting

Ann Arbor, Michigan, United States, 48105

Contacts

Lindsey Delott, MD

734-764-5106 ldelott@med.umich.edu

Clare McKolay

734-998-1962 delottlab@umich.edu

Principal Investigator:

Lindsey Delott, MD

Mayo Clinic in Rochester

Recruiting

Rochester, Minnesota, United States, 55905

Contacts

John Chen, MD, PhD

507-284-4946 chen.john@mayo.edu

Jessica Morgan

507-293-9689 morgan.jessica@mayo.edu

Principal Investigator:

John Jing-Wei Chen, MD, PhD

University of Mississippi Medical Center

Recruiting

Jackson, Mississippi, United States, 39216

Contacts

Melanie Truong-Le, DO, OD

601-984-2040 mtruongle@umc.edu

Marcus T Wells, MS

601-984-5046 MWells4@UMC.EDU

Principal Investigator:

Melanie Truong-Le, DO, OD

Icahn School of Medicine at Mount Sinai

Recruiting

New York, New York, United States, 10029

Contacts

Sammita Satyanarayan, MD

212-241-6854 sammita.satyanarayan@mssm.edu

Susan Filomena

212-241-3841 susan.e.filomena@mssm.edu

Principal Investigator:

Sammita Satyanarayan, MD

Columbia University

Recruiting

New York, New York, United States, 10032

Contacts

Kiran Kiran, MD

734-717-2160 ktt2115@cumc.columbia.edu

Gerome Vallejos

619-882-6469 gbv2110@cumc.columbia.edu

Principal Investigator:

Kiran Thakur, MD

Weill Cornell Medical College

Recruiting

New York, New York, United States, 10065

Contacts

Marc Dinkin, MD

646-962-2020 mjd2004@med.cornell.edu

Jaffer Shah

516-749-0058 jas4041@med.cornell.edu

Principal Investigator:

Marc Dinkin, MD

Duke University Health System

Recruiting

Durham, North Carolina, United States, 27710

Contacts

Nathan Tagg, MD

240-401-2631 nathan.tagg@duke.edu

Sarah Jones

919-681-6584 sarah.jones1@duke.edu

Principal Investigator:

Nathan Tagg, MD

University Hospitals Cleveland Medical Center

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Hesham Abboud, MD

216-844-5137 hesham.abboud@uhhospitals.org

Stacy Pot, BA

216-844-5605 stacy.pot@uhhospitals.org

Principal Investigator:

Hesham Hesham, MD

Oregon Health & Sciences University

Recruiting

Portland, Oregon, United States, 97239

Contacts

Elizabeth Silbermann, MD

515-991-4457 silberme@ohsu.edu

Jamie Anderson

503-494-1986 ajamie@ohsu.edu

Principal Investigator:

Elizabeth Silbermann, MD

University of Pittsburgh Medical Center, Magee Hospital

Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Contacts

Ingrid Loma-Miller, MD

412-641-6600 lomamilleri@upmc.edu

Courtney Skasik

717-395-2614 skasikca@upmc.edu

Principal Investigator:

Ingrid Loma-Miller, MD

Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Reid Longmuir, MD

615-936-2020 reid.longmuir@vumc.org

Hani Rashed

615-875-8670 hani.rashed@vumc.org

Principal Investigator:

Reid Longmuir, MD

UT Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75390

Contacts

Peter Sguigna, MD

214-645-0286 Peter.Sguigna@UTSouthwestern.edu

Taylor Hinojo, MS

214-645-3230 Taylor.Hinojo@UTSouthwestern.edu

Principal Investigator:

Peter Sguigna, MD

University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

Contacts

Stacey Clardy, MD

801-585-7575 stacey.clardy@hsc.utah.edu

Trieste Francis

801-587-3864 Trieste.Francis@hsc.utah.edu

Principal Investigator:

Stacey Clardy, MD

University of Virginia

Recruiting

Charlottesville, Virginia, United States, 22908

Contacts

Alexandra Simpson, MD

281-726-8081 zsk3ne@uvahealth.org

Matt Baron

434-297-4102 ukx3sv@uvahealth.org

Principal Investigator:

Alexandra Simpson, MD

University of Washington

Recruiting

Seattle, Washington, United States, 98195

Contacts

Yujie Wang, MD

832-628-3220 yujie@uw.edu

Courtney Francis

francis3@uw.edu

Principal Investigator:

Yujie Wang, MD

More Information

Sponsor

Mayo Clinic

Last update posted

Jul 6, 2026

Last verified

Jul, 2026

Keywords

Plasma Exchange
Plasmapheresis
Apheresis
Pheresis

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Mayo Clinic on 2026-07-06.