A Multicenter Study of Continued Current Therapy vs Transition to Ofatumumab After Neurofilament (NfL) Elevation (SOSTOS)
Primary Purpose
Relapsing-Remitting Multiple Sclerosis
Status
Recruiting
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Ofatumumab
Disease modifying treatment (DMT)
Sponsored by
About this trial
This is an interventional treatment trial for Relapsing-Remitting Multiple Sclerosis focused on measuring Ofatumumab, Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis, adult, OMB157, RRMS, MS, secondary progressive MS, relapse
Eligibility Criteria
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
Sites / Locations
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
- Novartis Investigative SiteRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Ofatumumab
DMT continued therapy
Arm Description
20 mg
Participants randomized to the continued therapy arm will continue to take their disease modifying treatment (DMT) as prescribed commercially by their physician.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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)
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.
Percentage of participants without a worsening of their disability
No increase or worsening of disability
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.
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.
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.
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.
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.
Mean change in Gd+ lesion count
Increase in the number of contrast-enhancing lesions on MRI
Mean change in Gd+ lesion volume
Increase in size of contrast-enhancing lesions on MRI
Mean change in T2 lesion count
Increase in new T2 lesions on MRI
Mean change in T2 lesion volume
Increase in size of T2 lesions on MRI
Mean change from Baseline in T1
Presence of new or enlarged T1 lesions
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.
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.
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
Full Information
NCT ID
NCT05090371
First Posted
October 12, 2021
Last Updated
October 9, 2023
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT05090371
Brief Title
A Multicenter Study of Continued Current Therapy vs Transition to Ofatumumab After Neurofilament (NfL) Elevation
Acronym
SOSTOS
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 2, 2022 (Actual)
Primary Completion Date
February 20, 2026 (Anticipated)
Study Completion Date
February 20, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsing-Remitting Multiple Sclerosis
Keywords
Ofatumumab, Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis, adult, OMB157, RRMS, MS, secondary progressive MS, relapse
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
A randomized, open label, multi-center, active-comparator study
Masking
None (Open Label)
Allocation
Randomized
Enrollment
150 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Ofatumumab
Arm Type
Experimental
Arm Description
20 mg
Arm Title
DMT continued therapy
Arm Type
Active Comparator
Arm Description
Participants randomized to the continued therapy arm will continue to take their disease modifying treatment (DMT) as prescribed commercially by their physician.
Intervention Type
Drug
Intervention Name(s)
Ofatumumab
Intervention Description
3 loading doses followed by administration every 4 weeks as per label
Intervention Type
Drug
Intervention Name(s)
Disease modifying treatment (DMT)
Intervention Description
Other DMT with approved label use for treatment which participants were on at least 6 months prior to Screening
Primary Outcome Measure Information:
Title
Percentage of participants achieving NEDA-3 (No Evidence of Disease Activity-3)
Description
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.
Time Frame
Months 3 to 15
Secondary Outcome Measure Information:
Title
Percentage of participants with a single baseline NfL≥10pg/ml and NfL<10pg/ml achieving NEDA-3 (No Evidence of Disease Activity-3)
Description
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)
Time Frame
Months 3 to15
Title
Annualized relapse rate in Months 3 to 15
Description
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.
Time Frame
Months 3 to 15
Title
Percentage of participants without a worsening of their disability
Description
No increase or worsening of disability
Time Frame
Months 3 to 15
Title
Percentage of participants with NEDA (No Evidence of Disease Activity) - Clinical
Description
A participant is considered as achieved NEDA-clinical is no clinical relapse or disease progression (by EDSS) has occurred.
Time Frame
Months 3 to 15
Title
Percentage of participants with NEDA (No Evidence of Disease Activity) - Radiological
Description
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.
Time Frame
Months 3 to 15
Title
Mean change in The Symbol-Digit Modality Test
Description
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.
Time Frame
Baseline, Months 3 and 15
Title
Mean change in the Time 25 Foot Walk
Description
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.
Time Frame
Baseline, Months 3 and 15
Title
Mean change in the 9 Hole Peg Test
Description
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.
Time Frame
Baseline, Months 3 and 15
Title
Mean change in Gd+ lesion count
Description
Increase in the number of contrast-enhancing lesions on MRI
Time Frame
Baseline, Months 3 and 15
Title
Mean change in Gd+ lesion volume
Description
Increase in size of contrast-enhancing lesions on MRI
Time Frame
Baseline, Months 3 and 15
Title
Mean change in T2 lesion count
Description
Increase in new T2 lesions on MRI
Time Frame
Baseline, Months 3 and 15
Title
Mean change in T2 lesion volume
Description
Increase in size of T2 lesions on MRI
Time Frame
Baseline, Months 3 and 15
Title
Mean change from Baseline in T1
Description
Presence of new or enlarged T1 lesions
Time Frame
Baseline up to Month 15
Title
Mean change in MSQOL-54
Description
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.
Time Frame
Month 3 to Month 15
Title
Mean whole brain and regional volume loss from Baseline
Description
Brain volume loss is a marker of progressive loss of brain structure and function. It is a predictor of disability progression.
Time Frame
Baseline up to Month 15
Title
Percentage of participants reporting treatment emergent adverse events (TEAEs) and serious adverse events
Description
Adverse events (TEAEs) and serious adverse events will be reported at each visit
Time Frame
Baseline up to Month 15
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
1-888-669-6682
Email
novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Facility Information:
Facility Name
Novartis Investigative Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35209
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Cullman
State/Province
Alabama
ZIP/Postal Code
35058
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85032
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Torrance
State/Province
California
ZIP/Postal Code
90509-2004
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Altamonte Springs
State/Province
Florida
ZIP/Postal Code
32714
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Maitland
State/Province
Florida
ZIP/Postal Code
32751
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Pensacola
State/Province
Florida
ZIP/Postal Code
32514
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Coeur d'Alene
State/Province
Idaho
ZIP/Postal Code
83815
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Alexandria
State/Province
Louisiana
ZIP/Postal Code
71301
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Lutherville
State/Province
Maryland
ZIP/Postal Code
21093
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01608
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202 2689
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Owosso
State/Province
Michigan
ZIP/Postal Code
48867
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28210
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37922
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77074
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Lubbock
State/Province
Texas
ZIP/Postal Code
79410
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Webster
State/Province
Texas
ZIP/Postal Code
77598
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Virginia Beach
State/Province
Virginia
ZIP/Postal Code
23456
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kirkland
State/Province
Washington
ZIP/Postal Code
98034
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122-4379
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54311
Country
United States
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T 2B5
Country
Canada
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Levis
State/Province
Quebec
ZIP/Postal Code
G6W 0M5
Country
Canada
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
Learn more about this trial
A Multicenter Study of Continued Current Therapy vs Transition to Ofatumumab After Neurofilament (NfL) Elevation
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