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

• Conditions: Tomography, Optical Coherence; Multiple Sclerosis; Retinal Degeneration; Visual Acuity
• Interventions: Drug: Ofatumumab

• Registration Number: NCT06167642
• Lead Sponsor: Johns Hopkins University

Brief Summary

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

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.

Study Timeline

• Study Start: 2023-05-22
• Study First Submitted: 2023-11-15
• Study First Submitted QC: 2023-12-04
• Study First Posted: 2023-12-12
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-09
• Last Update Posted: 2024-12-12
• Primary Completion: 2025-06
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

1. Between 18 - 70 years of age

2. 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.

3. Willing to sign informed consent

4. Willing to undergo phlebotomy

Exclusion Criteria

• Uncontrolled Diabetes
• Uncontrolled Hypertension
• Glaucoma
• Refractive errors of +/- 6 diopters
• Other neurologic or ophthalmologic disorders

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
People with RMS due to commence or already receiving ofatumumab therapy	Ofatumumab	75 people with RMS due to commence or already receiving ofatumumab therapy within 60 days of baseline.

Primary Outcome Measures

Name	Time	Method
Ganglion cell inner plexiform (GCIP) atrophy in RMS relative to HCs, according to baseline sNfL levels	at least 12 months for up to 2 years	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.

Secondary Outcome Measures

Name	Time	Method
Outer nuclear layer (ONL) atrophy in RMS relative to HCs	at least 12 months for up to 2 years	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.
Differences in the visual function scores	at least 12 months for up to 2 years	Exploratory analyses within the ofatumumab group will assess changes in visual function scores by baseline sNfL levels utilizing logistic regression.
Inner nuclear layer (INL) atrophy in RMS relative to HCs	at least 12 months for up to 2 years	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.
Differences in expanded disability status scale (EDSS) scores	at least 12 months for up to 2 years	Exploratory analyses within the ofatumumab group will assess changes in EDSS scores by baseline sNfL levels utilizing logistic regression.

Trial Locations

Locations (1)

Johns Hopkins; 🇺🇸 Baltimore, Maryland, United States