Clinical trial NCT06453694: Efgartigimod for the Treatment of Acute Optic Neuritis
Official title: A Pilot Randomized Trial of Efgartigimod Alfa for the Treatment of Incident Moderate to Severe Acute Optic Neuritis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Optic Neuritis
Keywords: Optic neuritis
Inflammatory optic neuropathy
Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD)
Neuromyelitis Optica Spectrum Disorder (NMOSD)
Multiple Sclerosis
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: argenx
First posted: 2024-06-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: This study is designed as a pilot, single-site, randomized, placebo-controlled, 2-arm, parallel-group clinical trial comparing efgartigimod alfa in addition to standard of care (IV steroids with a standardized oral taper) to standard of care with placebo, with an option for rescue therapy with plasma exchange for all participants in the case of poor therapeutic response.

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 1.5 Tesla (T) 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 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 within 1 month of treatment. Initiation of immunotherapy other than intravenous immunoglobulin (IVIG), plasma exchange, or rozanolixizumab more than 1 month after the second dose of efgartigimod is not an exclusion criterion and is permitted.
6. Known diagnosis of central nervous system (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 active study drug. 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.

Primary outcomes:
measure: Recruitment Rate
timeFrame: Through study completion, approximately 2 years
measure: Study Adherence Rate
timeFrame: Through study completion, approximately 2 years
measure: Change in high contrast visual acuity for effect size and standard deviation estimation
timeFrame: 1 month
measure: Change in low contrast visual acuity for effect size and standard deviation estimation
timeFrame: 1 month
Secondary outcomes:
measure: Retention rate
timeFrame: Through study completion, approximately 2 years
measure: Screen failure rate
timeFrame: Through study completion, approximately 2 years
measure: Pre-screen failure rate
timeFrame: Through study completion, approximately 2 years
measure: Drug adherence rate
timeFrame: Through study completion, approximately 2 years
measure: Full improvement in visual acuity (high contrast)
timeFrame: 30 days
measure: Full improvement in visual acuity (low contrast)
timeFrame: 30 days
measure: Personal maximal improvement (high contrast)
timeFrame: 30 days
measure: Personal maximal improvement (low contrast)
timeFrame: 30 days
measure: Improvement in high contrast visual acuity at 3 months
timeFrame: 3 months
measure: Improvement in high contrast visual acuity at 6 months
timeFrame: 6 months
measure: Rescue treatment
timeFrame: Day 7
measure: Difference in change in low contrast visual acuity from baseline to 6 months between groups
timeFrame: 3 months
measure: Difference in change in low contrast visual acuity from baseline to 6 months between groups
timeFrame: 6 months
measure: The number and proportion of participants with low contrast visual acuity of 0
timeFrame: 30 days
measure: Contrast sensitivity
timeFrame: 6 months
measure: Color Vision
timeFrame: 6 months
measure: Visual fields
timeFrame: 6 months
measure: Vision Related Quality of Life
timeFrame: 6 months
measure: Efgartigimod safety measures
timeFrame: 6 months
Other outcomes:
measure: Number and proportion of patients enrolled within 3, 5, 7, and 10 days of visual symptom onset
timeFrame: Day 0
measure: Contrast enhancement
timeFrame: Day 0
measure: Median duration (in days) from onset of blurry vision or visual acuity change to randomization
timeFrame: Day 0
measure: Median duration (in days) from onset of eye pain or headache to randomization
timeFrame: Day 0
measure: Number and proportion of overall participants with each diagnosis
timeFrame: Day 30
measure: Proportion amongst screened and recruited participants with HCVA of each visual acuity severity
timeFrame: Day 0
measure: Retinal nerve fiber layer (RNFL) thickness at 1 month between groups
timeFrame: 1 month
measure: Retinal nerve fiber layer (RNFL) thickness at 3 months between groups
timeFrame: 3 months
measure: Retinal nerve fiber layer (RNFL) thickness at 6 months between groups
timeFrame: 6 months
measure: Ganglion cell layer (GCL) thickness at 1 month between groups
timeFrame: 1 month
measure: Ganglion cell layer (GCL) thickness at 3 months between groups
timeFrame: 3 months
measure: Ganglion cell layer (GCL) thickness at 6 months between groups
timeFrame: 6 months
Locations:
city: Boston
country: United States
facility: Massachusetts Eye and Ear Infirmary
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Anastasia Vishnevetsky, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: