Efgartigimod for the Treatment of Acute Optic Neuritis

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

• Recruitment Rate [Срок оценки: 2 years]
• Study Adherence Rate [Срок оценки: 2 years]
• Change in high contrast visual acuity for effect size and standard deviation estimation [Срок оценки: 1 month]
• Change in low contrast visual acuity for effect size and standard deviation estimation [Срок оценки: 1 month]

Вторичные конечные точки (12)

• Retention rate [Срок оценки: 2 years]
• Screen failure rate [Срок оценки: 2 years]
• Pre-screen failure rate [Срок оценки: 2 years]
• Drug adherence rate [Срок оценки: 2 years]
• Full improvement in visual acuity (high contrast) [Срок оценки: 30 days]
• Full improvement in visual acuity (low contrast) [Срок оценки: 30 days]
• Personal maximal improvement (high contrast) [Срок оценки: 30 days]
• Personal maximal improvement (low contrast) [Срок оценки: 30 days]
• Improvement in high contrast visual acuity at 3 months [Срок оценки: 3 months]
• Improvement in high contrast visual acuity at 6 months [Срок оценки: 6 months]
• Rescue treatment [Срок оценки: Day 7]
• Difference in change in low contrast visual acuity from baseline to 6 months between groups [Срок оценки: 3 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Massachusetts Eye and Ear Infirmary — Boston
• Massachusetts General Hospital — Boston

Идентификаторы

NCT: NCT06453694 · pet-aon-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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