A Pilot Randomized Trial of Efgartigimod Alfa for the Treatment of Incident Moderate to Severe Acute Optic Neuritis
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 20
- Locations
- 2
- Primary Endpoint
- Change in low contrast visual acuity for effect size and standard deviation estimation
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Exclusion Criteria
- •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
- •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.
- •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
- •Incidental histological finding of prostate cancer (TNM stage T1a or T1b)
- •Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection
- •Clinically significant recent major surgery (within 1 month of screening), or intends to have surgery during the study
- •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.
Arms & Interventions
Efgartigmod alfa
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.
Intervention: Efgartigimod Alfa (Drug)
Placebo
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.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Change in low contrast visual acuity for effect size and standard deviation estimation
Time Frame: 1 month
Difference in change in low contrast visual acuity (LCVA) (# of letters seen at 2.5% illumination) from baseline to 1 month between groups
Change in high contrast visual acuity for effect size and standard deviation estimation
Time Frame: 1 month
Difference in change in high-contrast visual acuity from baseline to 1 month between groups
Recruitment Rate
Time Frame: 2 years
Number of enrolled participants per month
Study Adherence Rate
Time Frame: 2 years
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
Secondary Outcomes
- Retention rate(2 years)
- Screen failure rate(2 years)
- Pre-screen failure rate(2 years)
- Efgartigimod safety measures(6 months)
- Drug adherence rate(2 years)
- Full improvement in visual acuity (high contrast)(30 days)
- Full improvement in visual acuity (low contrast)(30 days)
- Personal maximal improvement (high contrast)(30 days)
- Personal maximal improvement (low contrast)(30 days)
- Improvement in high contrast visual acuity at 3 months(3 months)
- Improvement in high contrast visual acuity at 6 months(6 months)
- Rescue treatment(Day 7)
- Difference in change in low contrast visual acuity from baseline to 6 months between groups(6 months)
- The number and proportion of participants with low contrast visual acuity of 0(30 days)
- Contrast sensitivity(6 months)
- Color Vision(6 months)
- Visual fields(6 months)
- Vision Related Quality of Life(6 months)
Investigators
Anastasia Vishnevetsky, MD, MPH
Attending Physician in Neurology
Massachusetts General Hospital