Efgartigimod for the Treatment of Acute Optic Neuritis

Optic Neuritis Clinical Trial

— PET-AON  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06453694
• Other study ID #: pet-aon-001
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: October 2024
• Est. completion date: July 2027

Study information

• Verified date: June 2024
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: July 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Neuritis
• Optic Neuritis

Intervention

Drug:
• Efgartigimod Alfa
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.
• Placebo
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.

Locations

Country	Name	City	State
United States	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Anastasia Vishnevetsky, MD, MPH	argenx

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number and proportion of patients enrolled within 3, 5, 7, and 10 days of visual symptom onset	Number and proportion of patients enrolled within 3, 5, 7, and 10 days of visual symptom onset	Day 0
Other	Contrast enhancement	Number and proportion of patients enrolled with contrast enhancement of the optic nerves on MRI	Day 0
Other	Median duration (in days) from onset of blurry vision or visual acuity change to randomization	Median duration (in days) from onset of blurry vision or visual acuity change to randomization	Day 0
Other	Median duration (in days) from onset of eye pain or headache to randomization	Median duration (in days) from onset of eye pain or headache to randomization	Day 0
Other	Number and proportion of overall participants with each diagnosis	Number and proportion of overall participants with a final diagnosis of AQP4+ NMOSD, seronegative NMOSD, MOGAD, MS-related optic neuritis, idiopathic acute optic neuritis, or other diagnosis	Day 30
Other	Proportion amongst screened and recruited participants with HCVA of each visual acuity severity	Proportion amongst screened and recruited participants with HCVA worse than logMAR 0.48 (20/60), logMAR 0.7 (20/100), and logMAR 1 (20/200)	Day 0
Other	Retinal nerve fiber layer (RNFL) thickness at 1 month between groups	Retinal nerve fiber layer (RNFL) thickness at 1 month between groups	1 month
Other	Retinal nerve fiber layer (RNFL) thickness at 3 months between groups	Retinal nerve fiber layer (RNFL) thickness at 3 months between groups	3 months
Other	Retinal nerve fiber layer (RNFL) thickness at 6 months between groups	Retinal nerve fiber layer (RNFL) thickness at 6 months between groups	6 months
Other	Ganglion cell layer (GCL) thickness at 1 month between groups	Ganglion cell layer (GCL) thickness at 1 month between groups	1 month
Other	Ganglion cell layer (GCL) thickness at 3 months between groups	Ganglion cell layer (GCL) thickness at 3 months between groups	3 months
Other	Ganglion cell layer (GCL) thickness at 6 months between groups	Ganglion cell layer (GCL) thickness at 6 months between groups	6 months
Primary	Recruitment Rate	Number of enrolled participants per month	Through study completion, approximately 2 years
Primary	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	Through study completion, approximately 2 years
Primary	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
Primary	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	Retention rate	Percentage of enrolled subjects who remain in the study and do not voluntarily withdraw	Through study completion, approximately 2 years
Secondary	Screen failure rate	Percentage of participants who fail screening	Through study completion, approximately 2 years
Secondary	Pre-screen failure rate	Percentage of participants who fail pre-screening	Through study completion, approximately 2 years
Secondary	Drug adherence rate	Percentage of randomized participants who receive 2 full doses of their assigned study intervention	Through study completion, approximately 2 years
Secondary	Full improvement in visual acuity (high contrast)	Proportion of participants with full improvement in high contrast visual acuity	30 days
Secondary	Full improvement in visual acuity (low contrast)	Proportion of participants with full improvement in low contrast visual acuity	30 days
Secondary	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)	30 days
Secondary	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)	30 days
Secondary	Improvement in high contrast visual acuity at 3 months	Difference in change in high contrast visual acuity from baseline to 3 months between groups	3 months
Secondary	Improvement in high contrast visual acuity at 6 months	Difference in change in high contrast visual acuity from baseline to 6 months between groups	6 months
Secondary	Rescue treatment	Number and proportion of patients in each arm requiring rescue treatment	Day 7
Secondary	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	3 months
Secondary	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	6 months
Secondary	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	30 days
Secondary	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	6 months
Secondary	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).	6 months
Secondary	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.	6 months
Secondary	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	6 months
Secondary	Efgartigimod safety measures	Frequency and type of overall adverse events, treatment-related adverse events, and serious adverse events	6 months