Optic NeuritisPhase 2PET-AONNCT06453694
Efgartigimod for the Treatment of Acute Optic Neuritis
A Phase 2 study testing Efgartigimod Alfa in people with Optic Neuritis, run by Anastasia Vishnevetsky, MD, MPH at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Optic Neuritis
- What is being tested?
- Efgartigimod Alfa
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- 12 Aug 2025to Jun 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Massachusetts Eye and Ear Infirmary
Boston, Massachusetts, 02114
Marc Bouffard, MD, (617) 523-7900, Marc_Bouffard@MEEI.HARVARD.EDU
Marc Bouffard, MD
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Anastasia Vishnevetsky, MD, MPH, 617-726-8639, avishnevetsky@mgb.org
Anastasia Vishnevetsky, MD, MPH
About this study
Official title: A Pilot Randomized Trial of Efgartigimod Alfa for the Treatment of Incident Moderate to Severe Acute Optic Neuritis
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
Read the 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.
- Conditions
- Optic Neuritis
- Being tested
- Efgartigimod Alfa, Placebo
- Keywords
- Optic neuritis, Inflammatory optic neuropathy, Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD), Neuromyelitis Optica Spectrum Disorder (NMOSD), Multiple Sclerosis
- Medical subject headings
- Optic Neuritis, Neuromyelitis Optica, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Efgartigimod AlfaDrug
Also called Vyvgart Hytrulo
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment Rate
Number of enrolled participants per month
Measured: 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
Measured: 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
Measured: 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
Measured: 1 month
Secondary outcomes (19)
Retention rate
Percentage of enrolled subjects who remain in the study and do not voluntarily withdraw
Measured: 2 years
Screen failure rate
Percentage of participants who fail screening
Measured: 2 years
Pre-screen failure rate
Percentage of participants who fail pre-screening
Measured: 2 years
Drug adherence rate
Percentage of randomized participants who receive 2 full doses of their assigned study intervention
Measured: 2 years
Full improvement in visual acuity (high contrast)
Proportion of participants with full improvement in high contrast visual acuity
Measured: 30 days
Full improvement in visual acuity (low contrast)
Proportion of participants with full improvement in low contrast visual acuity
Measured: 30 days
Personal maximal improvement (high contrast)
Proportion of participants with personal maximal improvement in high contrast visual acuity (defined as individual final visual acuity at 6 months)
Measured: 30 days
Personal maximal improvement (low contrast)
Proportion of participants with personal maximal improvement in high contrast visual acuity (defined as individual final visual acuity at 6 months)
Measured: 30 days
Improvement in high contrast visual acuity at 3 months
Difference in change in high contrast visual acuity from baseline to 3 months between groups
Measured: 3 months
Improvement in high contrast visual acuity at 6 months
Difference in change in high contrast visual acuity from baseline to 6 months between groups
Measured: 6 months
Rescue treatment
Number and proportion of patients in each arm requiring rescue treatment
Measured: Day 7
Difference in change in low contrast visual acuity from baseline to 6 months between groups
Difference in change in low contrast visual acuity (# of letters seen at 2.5% illumination) from baseline to 3 months between groups
Measured: 3 months
Difference in change in low contrast visual acuity from baseline to 6 months between groups
Difference in change in low contrast visual acuity (# of letters seen at 2.5% illumination) from baseline to 6 months between groups
Measured: 6 months
The number and proportion of participants with low contrast visual acuity of 0
The number and proportion of participants with low contrast visual acuity of 0
Measured: 30 days
Contrast sensitivity
Difference in change in Pelli-Robson contrast sensitivity score (# of letters seen at 2.5% illumination) from baseline to each assessment time point between groups
Measured: 6 months
Color Vision
Difference in change in Hardy-Rand-Rittler color vision score from baseline to each assessment time point between groups. Scores range from 0 (lowest) to 6 (highest).
Measured: 6 months
Visual fields
Difference in change in Humphrey Visual fields score from baseline to each assessment time point between groups. Data derived from automated perimetry are continuous and expressed in decibels. The mean deviation calculated from a Humphrey Visual Field analyzer (24-2 fast paradigm) represents the difference between an individual's test performance and the performance of a normally-sighted control of the same age.
Measured: 6 months
Vision Related Quality of Life
National Eye Institute Visual Functioning Questionnaire (VFQ-25) scores at baseline, 1 month, 3 months, and 6 months in each arm. Scores range from 0 = worst to 100 = best
Measured: 6 months
Efgartigimod safety measures
Frequency and type of overall adverse events, treatment-related adverse events, and serious adverse events
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2024
- Study start12 Aug 2025
- Primary completionJun 2027 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Optic NeuritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Anastasia Vishnevetsky, MD, MPH
- Sponsor type
- University, hospital or other
- Collaborators
- argenx
- Responsible party
- Sponsor-investigator, Anastasia Vishnevetsky, MD, MPH, Massachusetts General Hospital
- Investigators
- Anastasia Vishnevetsky, MD, MPH, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06453694
- Sponsor's protocol ID
- pet-aon-001
- Acronym
- PET-AON
- Status last verified
- Oct 2026
- First submitted
- 30 May 2024
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Randomized Trial of Efgartigimod Alfa for the Treatment of Incident Moderate to Severe Acute Optic Neuritis
- ClinicalTrials.gov ID
- NCT06453694
- Acronym / sponsor ID
- PET-AON / pet-aon-001
- Conditions
- Optic Neuritis
- Keywords
- Optic neuritis, Inflammatory optic neuropathy, Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOGAD), Neuromyelitis Optica Spectrum Disorder (NMOSD), Multiple Sclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Anastasia Vishnevetsky, MD, MPHUniversity, hospital or other
- Collaborators
- argenx
- Study start
- 12 Aug 2025 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 12 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Efgartigmod alfa | Active comparator | Drug: Efgartigimod Alfa10 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. |
| Placebo | Placebo comparator | Drug: Placebo10 patients will receive placebo. All participants will receive standard of care high dose corticosteroids for 3 days with a prednisone taper over 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Efgartigimod AlfaAlso: Vyvgart Hytrulo2,016 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. | Drug | Efgartigmod alfa |
| PlaceboSubcutaneous 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. | Drug | Placebo |
Primary outcome
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
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
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
19 secondary outcomes
Retention rate
Time frame: 2 years
Screen failure rate
Time frame: 2 years
Pre-screen failure rate
Time frame: 2 years
Drug adherence rate
Time frame: 2 years
Full improvement in visual acuity (high contrast)
Time frame: 30 days
Full improvement in visual acuity (low contrast)
Time frame: 30 days
Personal maximal improvement (high contrast)
Time frame: 30 days
Personal maximal improvement (low contrast)
Time frame: 30 days
Improvement in high contrast visual acuity at 3 months
Time frame: 3 months
Improvement in high contrast visual acuity at 6 months
Time frame: 6 months
Rescue treatment
Time frame: Day 7
Difference in change in low contrast visual acuity from baseline to 6 months between groups
Time frame: 3 months
Difference in change in low contrast visual acuity from baseline to 6 months between groups
Time frame: 6 months
The number and proportion of participants with low contrast visual acuity of 0
Time frame: 30 days
Contrast sensitivity
Time frame: 6 months
Color Vision
Time frame: 6 months
Visual fields
Time frame: 6 months
Vision Related Quality of Life
Time frame: 6 months
Efgartigimod safety measures
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Massachusetts Eye and Ear Infirmary
Boston, United States
Anastasia Vishnevetsky, MD, MPH principal investigator
Massachusetts General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Efgartigimod Alfa in people with Optic Neuritis, run by Anastasia Vishnevetsky, MD, MPH at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment Rate (time frame: 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.