Efgartigimod for the Treatment of Acute Optic Neuritis

NCT06453694 | Recruiting Phase 2 FDA Drug

• 1 other identifier: pet-aon-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this pilot clinical trial is to test efgartigimod alfa against placebo in adults with first-time optic neuritis (optic nerve inflammation). The main questions it aims to answer are:

• Is it feasible to use efgartigimod alfa for optic neuritis?
• Is it feasible to run a larger trial testing efgartigimod alfa in optic neuritis?
• Does efgartigimod alfa work better than placebo in improving how quickly and how much vision returns? Participants will:
• have their vision and blood tested
• be asked questions about their vision
• will receive standard of care treatment with steroids regardless of whether they are receiving efgartigimod alfa or not
• will have periodic visits over 6 months

Conditions

Optic Neuritis

Keywords

Optic neuritis; Inflammatory optic neuropathy; Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD); Neuromyelitis Optica Spectrum Disorder (NMOSD); Multiple Sclerosis

Outcome Measures

Primary Outcomes (4)

• Recruitment Rate

  Number of enrolled participants per month

  2 years

• Study Adherence Rate

  Proportion of randomized participants who receive both doses of assigned study intervention, attend all assigned study visits, and complete at least the high contrast visual acuity, low contrast visual acuity, and Pelli-Robson assessments at all visits

  2 years

• Change in high contrast visual acuity for effect size and standard deviation estimation

  Difference in change in high-contrast visual acuity from baseline to 1 month between groups

  1 month

• Change in low contrast visual acuity for effect size and standard deviation estimation

  Difference in change in low contrast visual acuity (LCVA) (# of letters seen at 2.5% illumination) from baseline to 1 month between groups

  1 month

Secondary Outcomes (19)

• Retention rate

  2 years

• Screen failure rate

  2 years

• Pre-screen failure rate

  2 years

• Drug adherence rate

  2 years

• Full improvement in visual acuity (high contrast)

  30 days

Other Outcomes (12)

• Number and proportion of patients enrolled within 3, 5, 7, and 10 days of visual symptom onset

  Day 0

• Contrast enhancement

  Day 0

• Median duration (in days) from onset of blurry vision or visual acuity change to randomization

  Day 0

Study Arms (2)

Efgartigmod alfa

ACTIVE COMPARATOR

10 patients will receive efgartigimod alfa All participants will receive standard of care high dose corticosteroids for 3 days with a prednisone taper over 3 weeks.

Drug: Efgartigimod Alfa

Placebo

PLACEBO COMPARATOR

10 patients will receive placebo. All participants will receive standard of care high dose corticosteroids for 3 days with a prednisone taper over 3 weeks.

Drug: Placebo

Interventions

Efgartigimod Alfa DRUG

2,016 mg will be administered subcutaneously by a healthcare provider on Day 0 and Day 3 of the trial. Rescue therapy with therapeutic plasma exchange will be given to any participant based on the results of Day 7 evaluation.

Also known as: Vyvgart Hytrulo

Efgartigmod alfa

Placebo DRUG

Subcutaneous injection of placebo will be administered by a healthcare provider on Day 0 and Day 3 of the trial. Rescue therapy with therapeutic plasma exchange will be given to any participant based on the results of Day 7 evaluation.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Adults aged 18 years or older
• 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
• 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.
• 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.
• 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
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner

You may not qualify if:

• Current pregnancy or lactation
• Known allergic reactions or intolerance to efgartigimod, methylprednisolone, prednisone, or gadolinium or any of their components
• Known diagnosis of optic neuropathy preceding the current episode of optic neuritis
• Evidence of a systemic disease other than MS, NMOSD, or MOGAD that might be associated with the optic neuritis
• Known diagnosis of CNS demyelinating disease (MS, NMOSD, MOGAD) prior to present attack.
• 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.
• Alternative explanation for visual changes detected on fundoscopic exam and slit lamp examination.
• Enrollment in another clinical study involving an investigational treatment given within 2 months of enrollment in the present study.
• Contraindication to MRI or plasma exchange
• 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.
• Known HIV disease or common variable immunodeficiency
• 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:
• Basal cell or squamous cell skin cancer
• Carcinoma in situ of the cervix
• Carcinoma in situ of the breast

Sponsors & Collaborators

• Anastasia Vishnevetsky, MD, MPH: lead
• argenx: collaborator

Study Sites (2)

Massachusetts Eye and Ear Infirmary

Boston, Massachusetts, 02114, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

MeSH Terms

Conditions

Optic Neuritis; Neuromyelitis Optica; Multiple Sclerosis

Interventions

efgartigimod alfa

Condition Hierarchy (Ancestors)

Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Eye Diseases; Myelitis, Transverse; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Anastasia Vishnevetsky, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Attending Physician in Neurology

Study Record Dates

• First Submitted: May 30, 2024
• First Posted: June 12, 2024
• Study Start: August 12, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: November 10, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)