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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Relapsing-Remitting Multiple Sclerosis
• Intervention / Treatment: Drug: Ofatumumab; Drug: Disease modifying treatment (DMT)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 2B5
      • Recruiting
      • Novartis Investigative Site
  • Quebec
    • Granby, Quebec, Canada, J2G 1T7
      • Recruiting
      • Novartis Investigative Site
    • Levis, Quebec, Canada, G6W 0M5
      • Recruiting
      • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Recruiting
      • Novartis Investigative Site
    • Cullman, Alabama, United States, 35058
      • Recruiting
      • Novartis Investigative Site
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Recruiting
      • Novartis Investigative Site
  • California
    • Torrance, California, United States, 90509-2004
      • Recruiting
      • Novartis Investigative Site
  • Florida
    • Altamonte Springs, Florida, United States, 32714
      • Recruiting
      • Novartis Investigative Site
    • Maitland, Florida, United States, 32751
      • Recruiting
      • Novartis Investigative Site
    • Miami, Florida, United States, 33032
      • Recruiting
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32806
      • Recruiting
      • Novartis Investigative Site
    • Pensacola, Florida, United States, 32514
      • Recruiting
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Novartis Investigative Site
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83815
      • Recruiting
      • Novartis Investigative Site
  • Louisiana
    • Alexandria, Louisiana, United States, 71301
      • Recruiting
      • Novartis Investigative Site
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • Recruiting
      • Novartis Investigative Site
  • Massachusetts
    • Worcester, Massachusetts, United States, 01608
      • Recruiting
      • Novartis Investigative Site
  • Michigan
    • Detroit, Michigan, United States, 48202 2689
      • Recruiting
      • Novartis Investigative Site
    • Owosso, Michigan, United States, 48867
      • Recruiting
      • Novartis Investigative Site
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Recruiting
      • Novartis Investigative Site
  • New Jersey
    • Neptune, New Jersey, United States, 07753
      • Recruiting
      • Novartis Investigative Site
  • New York
    • Syracuse, New York, United States, 13210
      • Recruiting
      • Novartis Investigative Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-9500
      • Recruiting
      • Novartis Investigative Site
    • Charlotte, North Carolina, United States, 28210
      • Recruiting
      • Novartis Investigative Site
    • Raleigh, North Carolina, United States, 27607
      • Recruiting
      • Novartis Investigative Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37922
      • Recruiting
      • Novartis Investigative Site
  • Texas
    • Houston, Texas, United States, 77074
      • Recruiting
      • Novartis Investigative Site
    • Lubbock, Texas, United States, 79410
      • Recruiting
      • Novartis Investigative Site
    • Webster, Texas, United States, 77598
      • Recruiting
      • Novartis Investigative Site
  • Virginia
    • Virginia Beach, Virginia, United States, 23456
      • Recruiting
      • Novartis Investigative Site
  • Washington
    • Kirkland, Washington, United States, 98034
      • Recruiting
      • Novartis Investigative Site
    • Seattle, Washington, United States, 98122-4379
      • Recruiting
      • Novartis Investigative Site
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54311
      • Recruiting
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ofatumumab; 20 mg	Drug: Ofatumumab; 3 loading doses followed by administration every 4 weeks as per label
Active Comparator: DMT continued therapy; 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); Other DMT with approved label use for treatment which participants were on at least 6 months prior to Screening

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2022
• Primary Completion (Estimated): February 20, 2026
• Study Completion (Estimated): February 20, 2026

Study Registration Dates

• First Submitted: October 12, 2021
• First Submitted That Met QC Criteria: October 12, 2021
• First Posted (Actual): October 22, 2021

Study Record Updates

• Last Update Posted (Estimated): February 2, 2024
• Last Update Submitted That Met QC Criteria: February 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; adult; Ofatumumab; Relapsing-Remitting Multiple Sclerosis; OMB157; RRMS; MS; secondary progressive MS; relapse
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Antineoplastic Agents; Ofatumumab
• Other Study ID Numbers: COMB157GUS09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

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