ELIOS - Investigational Biomarkers to Track Disease Modification in Active RRMS

Phase 4

Recruiting

• Conditions: Relapsing Remitting Multiple Sclerosis (RRMS)

• Registration Number: NCT06733922
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

The exploratory ELIOS study aims to assess the value of novel investigational Eye Movement Biomarkers (EMBs) in tracking disease-related changes among a real-world cohort of Canadian patients with active RRMS, within the context of disease-modifying treatment (i.e., ofatumumab). To that end, the study will use the patented investigational, Eye Tracking Neurological Assessment (ETNA-ProgMS) SaMD (v1.0.11 or later), which has not yet received Health Canada approval, to reliably and accurately track eye movements with precision.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-12
• Study Start: 2024-11-27
• Study First Submitted QC: 2024-12-10
• Study First Posted: 2024-12-13
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-14
• Last Update Posted: 2025-03-18
• Primary Completion: 2027-11-22
• Study Completion: 2027-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 224

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
1- Change Eye Movement Biomarkers (EMB)	6 months from baseline	Change in subtle eye movement anomalies referred to as Eye Movement Biomarkers (EMBs). EMB are derived from composite scores of various Eye Movement metrics. Results stratified by patients experiencing a clinically meaningful change (CMC) in at least one traditional MS outcome (CMCp) or no CMC in all traditional MS outcomes (CMCs/i) at 24 months (or at the time of ofatumumab discontinuation and treated with ofatumumab for at least 12 months)

Secondary Outcome Measures

Name	Time	Method
1a. Change in EMB	3,12 and 24 months from Baseline	Change in subtle eye movement anomalies referred to as Eye Movement Biomarkers (EMBs). EMB are derived from composite scores of various Eye Movement metrics
1b. Change in EMB trajectories	3-, 6-, 12-, and 24-months	Trajectories of investigational EMBs over time
2a. Change in Annual Relapse Rate (ARR)	12 and 24 months from baseline	MS relapse is defined as the appearance of a new neurological abnormality or worsening of a previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. The abnormality must have been present for at least 24 hours and must have occurred in the absence of fever (\< 37.5°C) or of a known infection.
2b. Change in patient disability measured by Expanded Disability Status Scale EDSS	3,6,12,24 months from baseline	The EDSS is an ordinal scale used for assessing neurologic impairment in MS based on a neurological examination. It consists of scores in each of seven functional systems (FSs) and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 \[normal\] to 10 (death due to MS). The FSs are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel \& Bladder, and Cerebral functions
2b. Change in patient disability measured by Timed 25-foot walk test (T25-FW)	3,6,12,24 months from baseline	The T25- is an objective quantitative test of neurological function. It is an ambulation measurement assessing speed of walking: a timed (in seconds) walk of 25 feet (7.62 meters)
2b. Change in patient disability measured by the 9-hole peg test (9-HPT)	3,6,12,24 months from baseline	The 9- is an objective quantitative test of neurological function. It is measured to assess both right and left arm scores, the metric is the time, in seconds, required to insert and remove nine pegs. The 9-HPT will be administered 4 2 trials per hand, the time for each trial will be averaged with lower times indicating better performance
2c. Change in objective measures of cognitive impairment as measured by the Symbol Digit Modalities Test (SDMT)	3,6,12,24 months from baseline	The SDMT is an objective measure of information processing speed and associated cognitive dysfunction in patients with MS. Using a reference key, the patient has 90 seconds to pair specific numbers with given geometric figures in writing. The raw score corresponds to the total number of correct substitutions, ranging between 0 and 110 with higher scores indicative of better performance.
2c. Change in objective measures of cognitive impairment as measured by the Brief Visuospatial Memory Test (BVMT-R)	3,6,12,24 months from baseline	The BVMT-R is a measure of visuospatial learning, the test consists of six abstract symbols on a sheet of paper. Participants are given ten seconds to study the figures and then try to draw them in the same order on a blank page. Performance is scored on accuracy and location with 0-2 points per symbol for a maximum of 12 points per trial. Patients are asked to repeat the task three times with higher scores indicative of better performance
2c. Change in objective measures of cognitive impairment as measured by the Rey Auditory Verbal Learning Test (RAVLT)	3,6,12,24 months from baseline	The RAVLT is a test of verbal memory that requires the participant to learn and recall a list of 15 words that are orally presented. This test measures learning across five trials, retrieval of the target list after presenting a distracter list and a 30-minute delay, followed by recognition of the target words from among distracter words such as semantic and phonemic foils. The total learning score is the sum of correct answers across the five trials, with higher scores indicative of better performance.
3a. Association between EMB and annual relapse rate (AAR)	12 and 24 months	Association of change in each investigational EMB and ARR established at 12 and 24. To estimate the association of change between each investigational EMB and ARR a Poisson or Negative Binomial Generalized Linear Mixed Model (GLMM) will be used. The metric to assess the association of change over time between each investigational EMB and the outcome variable will be the fixed effect of investigational EMB on ARR, as estimated by the GLMM
3b. Association of EMBs and objective measures of disability - EDSS, T25-FW, and 9-HPT	Up to 24 months	Longitudinal associations of EMBs and objective measures of disability as measured by the EDSS, T25-FW, and 9-HPT. To estimate the longitudinal associations of change between investigational EMBs and measures of disability as measured by EDSS, T25-FW, and 9-HPT scores Linear Mixed Models (LMMs) with a random intercept will be used. The metric to assess the association of change over time between each investigational EMB and the outcome variable will be the population average fixed effect of each investigational EMB on the outcome, as estimated by the corresponding LMM
3c. Association of EMBs and objective measures of cognitive impairment - SDMT	Up to 24 months	Longitudinal associations of EMBs and objective measures of cognitive impairment as measured by the SDMT. To estimate the longitudinal associations of change between investigational EMBs and SDMT scores, Poisson GLMMs with a log link and a random intercept will be used. The metric to assess the association of change over time of investigational EMBs and the outcome variables will be the fixed effect of investigational EMBs on the outcomes, as estimated by the GLMMs
3c. Association of EMBs and objective measures of cognitive impairment - BVMT-R, and RAVLT	Up to 24 months	Longitudinal associations of EMBs and objective measures of cognitive impairment as measured by the BVMT-R and RAVLT. To estimate the longitudinal associations of change between investigational EMBs and measures of disability as measured by EDSS, T25-FW, and 9-HPT scores Linear Mixed Models (LMMs) with a random intercept will be used. The metric to assess the association of change over time between each investigational EMB and the outcome variable will be the population average fixed effect of each investigational EMB on the outcome, as estimated by the corresponding LMM
4. Change in serum Neurofilament light Chain (sNfL)	3,6,12,24 months from baseline	Change in NfL concentration in serum
5a. Change in patient-reported physical and psychological impact of MS disease as measured by the Multiple Sclerosis impact scale-29 version 2 (MSIS-29v2)	3,6,12,24 months from baseline	The MSIS-29v2 is a PRO measure that evaluates the physical and psychological effects of living with MS. The questionnaire consists of 29 items and is scored from 0 to 100, with higher scores indicating a more significant impact of MS.; The measure is divided into two subscales: a physical impact scale of 20 items, and a psychological impact scale of 9 items. All items consist of a four-point Likert-type response format: "not at all;" "a little;" "moderately;" and "extremely."
5b. Baseline assessment and change in patient-reported depression as measured by the Beck depression inventory-II (BDI-II)	3,6,12,24 months from baseline	The BDI-II scale is a measure that evaluates depression in patients with MS. It is a self-reported questionnaire that consists of 21 items that measures characteristic attitudes and symptoms of depression. Each item is scored 0 to 3 points for a total score range of 0 to 63. Low scores are associated with low levels of depression, while high scores are associated with high levels of depression
5c. Change in patient-reported cognitive impairment as measured by the MS neuropsychology questionnaire (MSNQ)	3,6,12,24 months from baseline	The MSNQ is a PRO that assesses perceived cognitive impairment among people with MS. It consists of 15 questions that cover different aspects of cognitive function, such as attention, planning, and language. The questions use a scale from 0 (never) to 4 (frequently) to indicate the frequency of cognitive difficulties.
5d. Change in patient-reported mobility as measured by the MS walking scale-12 version 1 (MSWS-12v1)	3,6,12,24 months from baseline	The 12-item MSWS is a PRO measure of the impact of MS on walking ability. The MSWS-12 consists of 12 questions that assess how much MS affects various aspects of walking, such as speed, balance, distance, and effort. The MSWS-12 is scored on a scale from 0 to 100, with higher scores indicating greater impairment
6. Incidence of treatment emergent adverse events and serious adverse events	24 months	Percentage of participants reporting treatment emergent adverse events and serious adverse events

Trial Locations

Locations (1)

Novartis Investigative Site; 🇨🇦 Quebec, Canada