Retinal Atrophy and Neurofilament Light Chain in People With Multiple Sclerosis Taking Ofatumumab

Study Overview
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Brief Summary
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This study aims to assess whether, and the degree to which, ofatumumab modulates or reduces rates of retinal atrophy in people with relapsing-remitting MS (RMS), according to baseline serum neurofilament light chain (sNfL) levels.

Detailed Description
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Seventy-five people with RMS who due to commence or already receiving ofatumumab therapy within 60 days of baseline will be recruited. All recruited participants will be tracked prospectively over a two-year period. Participants will complete an optical coherence tomography (OCT) scan, visual acuity (VA) assessments, EDSS, and sNfL blood level at baseline and every 6 months. Participants will be tracked prospectively for 2 years. OCT scans, sNfL levels, disability score determinations, 100% high-contrast, 2.5% and 1.25% low-contrast letter acuities will be performed every 6 months. Results from an existing cohort of approximately 75 healthy controls (HC) from a separate study undergoing annual OCT and visual function assessments will be used for comparison purposes.

Official Title
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Assessing the Modulation of Retinal Atrophy and Neurofilament Light Chain by Ofatumumab in Relapsing Multiple Sclerosis

Conditions
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Multiple Sclerosis, Tomography, Optical Coherence, Retinal Degeneration, Visual Acuity

Intervention / Treatment
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* Drug: Ofatumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Between 18 - 70 years of age Have RMS as confirmed by the treating neurologist based on the 2017 revised McDonald criteria AND Either be due to commence ofatumumab within 60 days of baseline OCT/VA/phlebotomy or be existing patients attending the center and already receiving ofatumumab, be eligible for inclusion, and already undergoing all of the proposed study procedures. Willing to sign informed consent Willing to undergo phlebotomy Exclusion Criteria: Uncontrolled Diabetes Uncontrolled Hypertension Glaucoma Refractive errors of +/- 6 diopters Other neurologic or ophthalmologic disorders

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| People with RMS due to commence or already receiving ofatumumab therapy<br>75 people with RMS due to commence or already receiving ofatumumab therapy within 60 days of baseline. | Drug: Ofatumumab<br>* Ofatumumab therapy is part of the patient's clinical care and is not given as part of the study<br>* Other names: Kesimpta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ganglion cell inner plexiform (GCIP) atrophy in RMS relative to HCs, according to baseline sNfL levels | Rates of of GCIP layer thinning (µm/year) will be assessed according to baseline sNfL levels using mixed-effects linear regression models with random subject and eye-specific random intercepts and random slopes in time, using time from baseline OCT visit (in years) as a continuous variable in both unadjusted models (including time, sNfL group and their interaction) and models adjusted for the cross-sectional and longitudinal effects of covariates (age, sex, race, and history of optic neuritis) by including these variables and their respective interactions with time. | at least 12 months for up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inner nuclear layer (INL) atrophy in RMS relative to HCs | Rates of INL layer thinning (µm/year) will be assessed according to baseline sNfL levels using mixed-effects linear regression models with random subject and eye-specific random intercepts and random slopes in time, using time from baseline OCT visit (in years) as a continuous variable in both unadjusted models (including time, sNfL group and their interaction) and models adjusted for the cross-sectional and longitudinal effects of covariates (age, sex, race, and history of optic neuritis) by including these variables and their respective interactions with time. | at least 12 months for up to 2 years | 
| Outer nuclear layer (ONL) atrophy in RMS relative to HCs | Rates of INL and ONL layer thinning (µm/year) will be assessed according to baseline sNfL levels using mixed-effects linear regression models with random subject and eye-specific random intercepts and random slopes in time, using time from baseline OCT visit (in years) as a continuous variable in both unadjusted models (including time, sNfL group and their interaction) and models adjusted for the cross-sectional and longitudinal effects of covariates (age, sex, race, and history of optic neuritis) by including these variables and their respective interactions with time. | at least 12 months for up to 2 years | 
| Differences in the visual function scores | Exploratory analyses within the ofatumumab group will assess changes in visual function scores by baseline sNfL levels utilizing logistic regression. | at least 12 months for up to 2 years | 
| Differences in expanded disability status scale (EDSS) scores | Exploratory analyses within the ofatumumab group will assess changes in EDSS scores by baseline sNfL levels utilizing logistic regression. | at least 12 months for up to 2 years |