A Multicenter Study of Continued Current Therapy vs Transition to Ofatumumab After Neurofilament (NfL) Elevation

Study Overview
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Brief Summary
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This study will evaluate if relapsing-remitting MS patients that have not had a relapse in the past year would benefit from a switch to ofatumumab versus staying on their continued current therapy. This study will also look at whether an elevated serum neurofilament light (NfL) level predicts enhanced benefit from a switch to ofatumumab.

Detailed Description
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This is a multicenter, prospective study of up to 150 relapsing-remitting MS participants/ The study is looking to see if patients who have not had a relapse in the past year would benefit from switching to ofatumumab. After giving consent, participants will have a 1 week screening/qualification period. If they qualify to continue, they will start a a six month run-in period during which lab samples will be collected. Patients that are relapse-free during the run-in period will continue into next period of the study in which they will be randomized to either ofatumumab or continued therapy for the next 15 months. Every 3 out of 5 randomized participants will be selected to wear a digital study watch to collect physical activity, sleep, and vitals during this 15 month period. The study watch will be worn 24 hours a day, 7 days a week but can be removed during showers/bathing. At the end of the 15 month period, a study completion visit will be held. The total study duration is 21 months plus 1 week for screening/qualification.

Official Title
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A Randomized, Open Label, Multi-center, Active-comparator Study to Assess Efficacy, Safety & Tolerability of Ofatumumab 20mg sc Monthly Versus Continued Current Therapy in Relapsing-remitting Multiple Sclerosis After Elevation of Serum Neurofilament Light Levels (SOSTOS)

Conditions
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Relapsing-Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: Ofatumumab
* Drug: Disease modifying treatment (DMT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Age 18-45 years Diagnosis of RRMS per McDonald Criteria (2017) EDSS 0-5.5 (Inclusive) Able to obtain MRI and attend study visits at sites Willing to use wearable device as specified in the protocol Able to provide blood sample On a current DMT with approved label use for treatment of RRMS at least 6 months prior to Screening No relapse reported within 6 months prior to Screening Patients may enroll in the trial if they have subclinical disease activity as measured by MRI prior to enrollment. An absence of MRI activity is not exclusionary. Exclusion Criteria: Primary progressive or secondary progressive phenotype Diseases other than multiple sclerosis responsible for the clinical or MRI presentation Use of experimental or investigational drugs for MS within 2 years from Screening Known sensitivity to gadolinium Central Nervous System (CNS) anomalies that are better accounted for by another disease process Known active malignancies Active chronic disease (or stable but treated with immune therapy) of the immune system other than MS Active infections including systemic bacterial, viral (including COVID-19) or fungal infections, known to have AIDS or tested positive for HIV antibodies Neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML), or confirmed PML IgG or IgM levels below lower limit of normal (LLN) at Screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized, open label, multi-center, active-comparator study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ofatumumab<br>20 mg | Drug: Ofatumumab<br>* 3 loading doses followed by administration every 4 weeks as per label<br>|
| Active Comparator: DMT continued therapy<br>Participants randomized to the continued therapy arm will continue to take their disease modifying treatment (DMT) as prescribed commercially by their physician. | Drug: Disease modifying treatment (DMT)<br>* Other DMT with approved label use for treatment which participants were on at least 6 months prior to Screening<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants achieving NEDA-3 (No Evidence of Disease Activity-3) | A participant is considered as achieved NEDA-3 if the participant has not had a clinical relapse (recurrence of a disease activity after a recovery), has not had an increase in disability and has no new radiological MRI activity (no new occurrences of contrast-enhancing lesions) during study Months 3 to 15. | Months 3 to 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with a single baseline NfL≥10pg/ml and NfL<10pg/ml achieving NEDA-3 (No Evidence of Disease Activity-3) | Participants with a single baseline NfL≥10 pg/ml and NfL<10pg/ml will be considered as achieved NEDA-3 if the participant has not had a clinical relapse (recurrence of a disease activity after a recovery), has not had an increase in disability and has no new radiological MRI activity (no new occurrences of contrast-enhancing lesions) | Months 3 to15 | 
| Annualized relapse rate in Months 3 to 15 | Relapses are recurrences of a disease activity after a recovery. A confirmed MS relapse is one accompanied by a clinically relevant change in the EDSS performed by the EDSS Rater, i.e. an increase of at least 0.5 points on the EDSS score, or an increase of 1 point on two functional scores (FSs) or 2 points on one FS, excluding changes involving bowel/bladder or cerebral FS compared to the previous available rating (the last EDSS rating that did not occur during a relapse). Confirmation of MS relapse based on these definitions will be done centrally. | Months 3 to 15 | 
| Percentage of participants without a worsening of their disability | No increase or worsening of disability | Months 3 to 15 | 
| Percentage of participants with NEDA (No Evidence of Disease Activity) - Clinical | A participant is considered as achieved NEDA-clinical is no clinical relapse or disease progression (by EDSS) has occurred. | Months 3 to 15 | 
| Percentage of participants with NEDA (No Evidence of Disease Activity) - Radiological | A participant is considered as achieved NEDA-radiological if the participant has has no new radiological MRI activity (no new occurrences of contrast-enhancing lesions) during study Months 3 to 15. | Months 3 to 15 | 
| Mean change in The Symbol-Digit Modality Test | This test measures cognition in patients with MS. Patients are asked to substitute a number, either orally or written, for randomized presentations of geometric figures. | Baseline, Months 3 and 15 | 
| Mean change in the Time 25 Foot Walk | This is a test of mobility and leg function. The patient is instructed to one end of a marked 25-foot course and is instructed to walk 25 feet as quickly as possible, but safely. The time to complete the test is calculated from the initiation of the instruction to start and ends when the patient has reached the 25-foot mark. The task is performed again when the patient is directed to walk back the same distance. A walking device is permitted during this test. | Baseline, Months 3 and 15 | 
| Mean change in the 9 Hole Peg Test | This is a test of upper extremity function. The patient is seated at a table with a small, shallow container holding nine pegs and a wood or plastic block containing nine empty holes. The patient picks up the nine pegs one at a time as quickly as possible, puts them in nine holes and once they are in the holes, the patient removes them again as quickly as possible one at a time, replacing them into the shallow container. The total time to complete the task is recorded. This test is performed with both the dominant and non-dominant hand. | Baseline, Months 3 and 15 | 
| Mean change in Gd+ lesion count | Increase in the number of contrast-enhancing lesions on MRI | Baseline, Months 3 and 15 | 
| Mean change in Gd+ lesion volume | Increase in size of contrast-enhancing lesions on MRI | Baseline, Months 3 and 15 | 
| Mean change in T2 lesion count | Increase in new T2 lesions on MRI | Baseline, Months 3 and 15 | 
| Mean change in T2 lesion volume | Increase in size of T2 lesions on MRI | Baseline, Months 3 and 15 | 
| Mean change from Baseline in T1 | Presence of new or enlarged T1 lesions | Baseline up to Month 15 | 
| Mean change in MSQOL-54 | The MSQOL-54 is health-related quality of life questionnaire that assesses the physical, mental, and social effects experienced by MS patients, as well as functional disability. It is made up for 54 questions with a total score ranging from.0 to 100. Higher scores indicate better quality of life. | Month 3 to Month 15 | 
| Mean whole brain and regional volume loss from Baseline | Brain volume loss is a marker of progressive loss of brain structure and function. It is a predictor of disability progression. | Baseline up to Month 15 | 
| Percentage of participants reporting treatment emergent adverse events (TEAEs) and serious adverse events | Adverse events (TEAEs) and serious adverse events will be reported at each visit | Baseline up to Month 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ofatumumab, Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis, adult, OMB157, RRMS, MS, secondary progressive MS, relapse