Efgartigimod to speed vision recovery in acute optic neuritis

A Pilot Randomized Trial of Efgartigimod Alfa for the Treatment of Incident Moderate to Severe Acute Optic Neuritis

This pilot will test whether efgartigimod given with standard steroids helps adults having their first episode of optic neuritis regain vision faster and more fully than placebo.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Massachusetts General Hospital (other)
• Drugs / interventions: immunotherapy, prednisone
• Locations: 2 sites (Boston, Massachusetts and 1 other locations)
• Trial ID: NCT06453694 on ClinicalTrials.gov

What this trial studies

This is a single-site, randomized, placebo-controlled, two-arm pilot trial comparing efgartigimod plus standard IV steroid therapy (with a standardized oral taper) against placebo plus the same steroid regimen. Participants will be adults with a first episode of optic neuritis confirmed by MRI and enrolled within 10 days of vision changes. Vision testing, blood tests, symptom questionnaires, and regular clinic visits will occur over a six-month follow-up, with an option for rescue plasma exchange for poor responders. The trial is designed to test feasibility and to provide preliminary data on speed and degree of visual recovery.

Who should consider this trial

Good fit: Adults (18 and older) who have a first episode of optic neuritis confirmed by MRI and can enroll within 10 days of vision changes and attend study visits are the intended participants.

Not a fit: People with recurrent optic neuritis, vision changes older than 10 days, or other exclusionary medical conditions are unlikely to benefit from or be eligible for this trial.

Why it matters

Potential benefit: If successful, efgartigimod added to steroids could help people with first-time optic neuritis recover vision more quickly and reduce lasting visual deficits.

How similar studies have performed: FcRn blockers like efgartigimod have shown benefit in other antibody-mediated neurological diseases, but their use specifically for optic neuritis is novel and unproven.

Eligibility criteria

Inclusion Criteria:

1. Provision of signed and dated informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Adults aged 18 years or older
4. Diagnosed with a first episode of optic neuritis, based on clinical presentation (i.e. typical features such as pain with eye movements, color vision changes, subacute presentation, and visual acuity loss) and confirmed by contrast enhancement or T2 hyperintensity of the optic nerve on MRI brain or orbits using a 1.5T MRI scanner or greater
5. Onset of optic neuritis-related vision changes (does not include headache, eye pain, or pain with eye movements), as defined by decreased visual acuity, subjectively reported blurred vision, or optic nerve enhancement on MRI brain or orbits, within 10 days (inclusive) of enrollment. If optic neuritis is bilateral, then enrollment must occur within 10 days of vision changes in the first affected eye.
6. Best-corrected high contrast visual acuity (HCVA) in the worse affected eye on the Early Treatment Diabetic Retinopathy Study (ETDRS) eye chart of logMAR 0.48 (20/60) or worse.
7. For females of reproductive potential: negative urine or serum pregnancy test at screening or use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 8 weeks after the end of efgartigimod administration
8. For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner

Exclusion Criteria:

1. Current pregnancy or lactation
2. Known allergic reactions or intolerance to efgartigimod, methylprednisolone, prednisone, or gadolinium or any of their components
3. Known diagnosis of optic neuropathy preceding the current episode of optic neuritis
4. Evidence of a systemic disease other than MS, NMOSD, or MOGAD that might be associated with the optic neuritis
5. Receiving systemic immunomodulatory or immunosuppressive therapy at the time of enrollment or planned receipt within 3 weeks of treatment. Initiation of immunotherapy more than 3 weeks after the second dose of efgartigimod is not an exclusion criterion and is permitted.
6. Known diagnosis of CNS demyelinating disease (MS, NMOSD, MOGAD) prior to present attack.
7. Any visually-significant ocular pathology (i.e. retinal problems, cataracts, glaucoma etc.) in the affected eye that led to known best-corrected visual acuity deficits in participants prior to onset of optic neuritis. Congenital color-blindness is not disqualifying.
8. Alternative explanation for visual changes detected on fundoscopic exam and slit lamp examination.
9. Enrollment in another clinical study involving an investigational treatment given within 2 months of enrollment in the present study.
10. Contraindication to MRI or plasma exchange
11. Has received \>3 days of high-dose steroids (IV or PO) for the treatment of the current episode of acute optic neuritis by the time of randomization. Randomization may occur at the latest on the next day after completion of 3rd dose of steroids.
12. Known HIV disease or common variable immunodeficiency
13. History of malignancy unless considered cured by adequate treatment with no evidence of recurrence for ≥1 year before the first administration of IMP. Adequately treated participants with the following cancers may be included at any time:

    1. Basal cell or squamous cell skin cancer
    2. Carcinoma in situ of the cervix
    3. Carcinoma in situ of the breast
    4. Incidental histological finding of prostate cancer (TNM stage T1a or T1b)
14. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection
15. Clinically significant recent major surgery (within 1 month of screening), or intends to have surgery during the study
16. Any conditions or circumstances that in the opinion of the investigator may put the participant at undue risk, confound the results of the study, or otherwise make the participant unsuitable for the study.

Where this trial is running

Boston, Massachusetts and 1 other locations

• Massachusetts Eye and Ear Infirmary — Boston, Massachusetts, United States (RECRUITING)
• Massachusetts General Hospital — Boston, Massachusetts, United States (RECRUITING)

Study contacts

• Principal investigator: Anastasia Vishnevetsky, MD, MPH — Massachusetts General Hospital

Conditions: Optic Neuritis, Optic neuritis, Inflammatory optic neuropathy, Myelin Oligodendrocyte Glycoprotein Antibody Disease, Neuromyelitis Optica Spectrum Disorder, Multiple Sclerosis