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

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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Multiple Sclerosis; Retinal Degeneration; Visual Acuity; Tomography, Optical Coherence
• Intervention / Treatment: Drug: Ofatumumab

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 Type: Observational
• Enrollment (Estimated): 75

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

75 people with RMS due to commence or already receiving ofatumumab therapy within 60 days of baseline OCT, VA, and blood draw.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
People with RMS due to commence or already receiving ofatumumab therapy; 75 people with RMS due to commence or already receiving ofatumumab therapy within 60 days of baseline.	Drug: Ofatumumab; Ofatumumab therapy is part of the patient's clinical care and is not given as part of the study; Other Names: Kesimpta

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: Novartis
• Investigators: Principal Investigator: Shiv Saidha, MBBCh, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: November 15, 2023
• First Submitted That Met QC Criteria: December 4, 2023
• First Posted (Actual): December 12, 2023

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Pathological Conditions, Anatomical; Autoimmune Diseases; Immune System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Eye Diseases, Hereditary; Retinal Diseases; Multiple Sclerosis; Sclerosis; Atrophy; Retinal Degeneration; Antineoplastic Agents; Ofatumumab
• Other Study ID Numbers: IRB00347678

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No