Efficacy and Safety of Ofatumumab Compared to Teriflunomide in Patients With Relapsing Multiple Sclerosis

Relapsing Multiple Sclerosis Clinical Trial

— ASCLEPIOS I  

Official title:

A Randomized, Double-blind, Double-dummy, Parallel-group Study Comparing the Efficacy and Safety of Ofatumumab Versus Teriflunomide in Patients With Relapsing Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02792218
• Other study ID #: COMB157G2301
• Secondary ID: 2015-005418-31
• Status: Completed
• Phase: Phase 3
• Start date: September 20, 2016
• Est. completion date: July 20, 2020

Study information

• Verified date: September 2021
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To compare the efficacy and safety of ofatumumab administered subcutaneously (sc) every 4 weeks versus teriflunomide administered orally once daily in patients with relapsing multiple sclerosis

Description:

This was a randomized, double-blind, double-dummy, active comparator-controlled, parallel-group, multi-center study with variable treatment duration in approximately 900 patients with relapsing multiple sclorosis (RMS). The maximal treatment duration in the study for an individual patient was 2.5 years. Eligible patients were randomized to receive either experimental ofatumumab subcutaneous (s.c.) injections every 4 weeks or active comparator teriflunomide orally once daily. The dose regimen for ofatumumab for this study was a loading dose regimen of 20 mg at Day 1, Day 7 and Day 14, followed by a maintenance dose regimen of 20 mg administered every 4 weeks starting at Week 4. In order to blind for the different formulations, double-dummy masking was used i.e. all patients will take injections (containing either active ofatumumab or placebo) and oral capsules (containing either active teriflunomide or placebo).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 930
• Est. completion date: July 20, 2020
• Est. primary completion date: July 5, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• 18 to 55 years of age
• Diagnosis of multiple sclerosis (MS)
• Relapsing MS: relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS)
• At least 1 relapse during the previous 1 year or 2 relapses during the previous 2 years or a positive gadolinium-enhancing MRI scan in previous year
• Expanded disability status scale (EDSS) score of 0 to 5.5

Exclusion Criteria:

• Primary progressive MS
• Disease duration of more than 10 years in patients with an EDSS score of 2 or less
• Patients with an active chronic disease of the immune system other than MS
• Patients at risk of developing or having reactivation of hepatitis
• Patients with active systemic infections or with neurological findings consistent with PML

Related Conditions & MeSH terms

• Multiple Sclerosis
• Relapsing Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Ofatumumab subcutaneous injection
Ofatumumab 20 mg pre-filled syringes for subcutaneous injection on days 1, 7, 14, week 4 and every 4 weeks thereafter
• Teriflunomide-matching placebo capsules
Placebo capsule, matching in appearance to teriflunomide, taken orally once daily
• Teriflunomide capsule
Teriflunomide 14 mg oral capsule taken once daily
• Matching placebo of ofatumumab subcutaneous injections
Matching placebo of ofatumumab subcutaneous injections on days 1, 7, 14, week 4 and every 4 weeks thereafter

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Australia	Novartis Investigative Site	New Lambton Heights	New South Wales
Australia	Novartis Investigative Site	St Leonards	New South Wales
Belgium	Novartis Investigative Site	Brasschaat
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Liege
Belgium	Novartis Investigative Site	Pelt
Bulgaria	Novartis Investigative Site	Plovdiv
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Canada	Novartis Investigative Site	Gatineau	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Vancouver	British Columbia
Croatia	Novartis Investigative Site	Rijeka	HRV
Croatia	Novartis Investigative Site	Zagreb
Czechia	Novartis Investigative Site	Hradec Kralove	CZE
Czechia	Novartis Investigative Site	JIhlava
Czechia	Novartis Investigative Site	Olomouc	CZE
Czechia	Novartis Investigative Site	Pardubice
Czechia	Novartis Investigative Site	Praha 4 Krc	Czech Republic
Czechia	Novartis Investigative Site	Praha 5
Denmark	Novartis Investigative Site	Aarhus
Denmark	Novartis Investigative Site	Copenhagen
Denmark	Novartis Investigative Site	Odense C
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Nancy	Cedex
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Nimes Cedex
Germany	Novartis Investigative Site	Barsinghausen
Germany	Novartis Investigative Site	Bayreuth
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Neuburg an der Donau
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Wiesbaden
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Thessaloniki
Hungary	Novartis Investigative Site	Budapest	HUN
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Kistarcsa
Hungary	Novartis Investigative Site	Szeged
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Chandigarh	Punjab
India	Novartis Investigative Site	Kochi	Kerala
India	Novartis Investigative Site	Kolkata	West Bengal
India	Novartis Investigative Site	Mangalore
India	Novartis Investigative Site	New Delhi	Delhi
Israel	Novartis Investigative Site	Ashkelon
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Sefad
Israel	Novartis Investigative Site	Tel Aviv
Italy	Novartis Investigative Site	Gallarate	VA
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Roma	RM
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Sittard-Geleen	BG
Poland	Novartis Investigative Site	Bydgoszcz
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Kielce
Poland	Novartis Investigative Site	Lodz
Puerto Rico	Novartis Investigative Site	Guaynabo
Russian Federation	Novartis Investigative Site	Kemerovo
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Nizhny Novgorod
Russian Federation	Novartis Investigative Site	Novosibirsk
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saransk
Russian Federation	Novartis Investigative Site	Sestroretsk
Russian Federation	Novartis Investigative Site	Tyumen
Slovakia	Novartis Investigative Site	Banska Bystrica
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Nitra
Slovakia	Novartis Investigative Site	Trnava
Spain	Novartis Investigative Site	Barcelona	Cataluna
Spain	Novartis Investigative Site	Barcelona	Cataluna
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Cadiz	Andalucia
Spain	Novartis Investigative Site	El Palmar	Murcia
Spain	Novartis Investigative Site	L Hospitalet De Llobregat	Catalunya
Spain	Novartis Investigative Site	Salt	Cataluña
Spain	Novartis Investigative Site	Valencia
Sweden	Novartis Investigative Site	Goeteborg
Sweden	Novartis Investigative Site	Stockholm
Switzerland	Novartis Investigative Site	Basel
Thailand	Novartis Investigative Site	Khon Kaen	THA
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Kocaeli
Turkey	Novartis Investigative Site	Samsun
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Headington	Oxfordshire
United Kingdom	Novartis Investigative Site	London
United States	Novartis Investigative Site	Alexandria	Louisiana
United States	Novartis Investigative Site	Atlantis	Florida
United States	Novartis Investigative Site	Baton Rouge	Louisiana
United States	Novartis Investigative Site	Berkeley	California
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Chesterfield	Missouri
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Clinton Township	Michigan
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Delray Beach	Florida
United States	Novartis Investigative Site	Des Moines	Iowa
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	El Paso	Texas
United States	Novartis Investigative Site	Fullerton	California
United States	Novartis Investigative Site	Golden Valley	Minnesota
United States	Novartis Investigative Site	Green Bay	Wisconsin
United States	Novartis Investigative Site	Hollywood	Florida
United States	Novartis Investigative Site	Honolulu	Hawaii
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Johnson City	Tennessee
United States	Novartis Investigative Site	Kansas City	Kansas
United States	Novartis Investigative Site	Knoxville	Tennessee
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Novartis Investigative Site	Latham	New York
United States	Novartis Investigative Site	Loxahatchee Groves	Florida
United States	Novartis Investigative Site	Madison	Wisconsin
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Milwaukee	Wisconsin
United States	Novartis Investigative Site	Naples	Florida
United States	Novartis Investigative Site	Neenah	Wisconsin
United States	Novartis Investigative Site	North Palm Beach	Florida
United States	Novartis Investigative Site	Northbrook	Illinois
United States	Novartis Investigative Site	Oklahoma City	Oklahoma
United States	Novartis Investigative Site	Overland Park	Kansas
United States	Novartis Investigative Site	Ozark	Missouri
United States	Novartis Investigative Site	Pensacola	Florida
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Port Charlotte	Florida
United States	Novartis Investigative Site	Raleigh	North Carolina
United States	Novartis Investigative Site	Round Rock	Texas
United States	Novartis Investigative Site	Sacramento	California
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Savannah	Georgia
United States	Novartis Investigative Site	Spartanburg	South Carolina
United States	Novartis Investigative Site	Sunrise	Florida
United States	Novartis Investigative Site	Vero Beach	Florida
United States	Novartis Investigative Site	Virginia Beach	Virginia
United States	Novartis Investigative Site	Washington	District of Columbia
United States	Novartis Investigative Site	West Palm Beach	Florida
United States	Novartis Investigative Site	Winston-Salem	North Carolina
United States	Novartis Investigative Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Bulgaria,  Canada,  Croatia,  Czechia,  Denmark,  Estonia,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Mexico,  Netherlands,  Poland,  Puerto Rico,  Russian Federation,  Slovakia,  Spain,  Sweden,  Switzerland,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized Relapse Rate (ARR)	ARR was the number of confirmed relapses in a year, calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of time in study. A confirmed MS relapse was defined as one accompanied by a clinically-relevant change in the EDSS performed by the Independent 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 or 2 points on one functional score (excluding changes involving bowel/bladder or cerebral functional system). Comparisons were made to the previous rating (the last EDSS rating that did not occur during a relapse).	Baseline up to 2.5 years
Secondary	3-month Confirmed Disability Worsening (3mCDW) Based on EDSS - Pooled Data	A 3-month confirmed disability worsening (3mCDW) was defined as an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 3 months. For patients with a baseline EDSS of 0, the criterion for disability worsening was an increase in EDSS of =1.5, for patients with a baseline EDSS of 1 to 5 or =5.5, the criterion for disability worsening was an increase in EDSS of =1 or =0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2302 to address this endpoint.	Baseline, every 3 months up to 2.5 years
Secondary	3-month Confirmed Disability Worsening (3mCDW) Based on EDSS - Study COMB157G2301	A 3-month confirmed disability worsening (3mCDW) was defined as an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 3 months. For patients with a baseline EDSS of 0, the criterion for disability worsening was an increase in EDSS of =1.5, for patients with a baseline EDSS of 1 to 5 or =5.5, the criterion for disability worsening was an increase in EDSS of =1 or =0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2302 to address this endpoint.	Baseline, every 3 months up to 2.5 years
Secondary	6-month Confirmed Disability Worsening (6mCDW) Based on EDSS - Pooled Data	A 6-month confirmed disability worsening (6mCDW) was defined as an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 6 months. For patients with a baseline EDSS of 0, the criterion for disability worsening was an increase in EDSS of =1.5, for patients with a baseline EDSS of 1 to 5 or =5.5, the criterion for disability worsening was an increase in EDSS of =1 or =0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2302 to address this endpoint.	Baseline, every 3 months up to 2.5 years
Secondary	6-month Confirmed Disability Worsening (6mCDW) Based on EDSS - Study COMB157G2301	A 6-month confirmed disability worsening (6mCDW) was defined as an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 6 months. For patients with a baseline EDSS of 0, the criterion for disability worsening was an increase in EDSS of =1.5, for patients with a baseline EDSS of 1 to 5 or =5.5, the criterion for disability worsening was an increase in EDSS of =1 or =0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2302 to address this endpoint.	Baseline, every 3 months up to 2.5 years
Secondary	6-month Confirmed Disability Improvement (6mCDI ) Based on EDSS - Pooled Data	A 6-month confirmed disability improvement (6mCDI) was defined as a decrease from baseline EDSS sustained for at least 6 months. For patients with a baseline EDSS of 0 to 1.5, no disability improvement was possible based on the protocol definition of an improvement; for patients with a baseline EDSS of =2 to 6 or =6.5 to 9.5, the criterion for disability improvement was a decrease in EDSS of =1 or =0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2302 to address this endpoint.	Baseline, every 3 months up to 2.5 years
Secondary	6-month Confirmed Disability Improvement (6mCDI ) Based on EDSS - Study COMB157G2301	A 6-month confirmed disability improvement (6mCDI) was defined as a decrease from baseline EDSS sustained for at least 6 months. For patients with a baseline EDSS of 0 to 1.5, no disability improvement was possible based on the protocol definition of an improvement; for patients with a baseline EDSS of =2 to 6 or =6.5 to 9.5, the criterion for disability improvement was a decrease in EDSS of =1 or =0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2302 to address this endpoint.	Baseline, every 3 months up to 2.5 years
Secondary	Number of Gd-enhancing T1 Lesions Per MRI Scan	Total number of Gd-enhancing T1 lesions across all scans per patient adjusted for different number of scans due to variable follow-up time in study.	Baseline, yearly up to 2.5 years
Secondary	Number of New or Enlarging T2 Lesions on MRI Per Year (Annualized Lesion Rate)	Number of new/enlarging T2 lesions on last available MRI scan compared to baseline adjusted for different time of scans versus baseline due to variable follow up time in study	Baseline, yearly up to 2.5 years
Secondary	Neurofilament Light Chain (NfL) Concentration in Serum	The NfL concentration (geometric mean concentration) was estimated by treatment and time point with using a repeated measures model on the basis of all evaluable log-transformed NfL values.	Month 3, 12 and 24
Secondary	Annualized Rate of Brain Volume Loss Based on Assessments of Percent Brain Volume Change From Baseline	Percent change from baseline in brain volume loss (BVL) on all MRI scans adjusted for different time of scan versus baseline due to variable follow up time in study	Baseline, months 12 and 24
Secondary	Percentage of Participants With Confirmed Relapse	A confirmed MS relapse was defined as one accompanied by a clinically-relevant change in the EDSS performed by the Independent 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 or 2 points on one functional score (excluding changes involving bowel/bladder or cerebral functional system).	Baseline up to 2.5 years
Secondary	Annualized Relapse Rate (ARR) >8 Weeks After Onset of Treatment	ARR was the number of confirmed relapses in a year, calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of time in study. A confirmed MS relapse was defined as one accompanied by a clinically-relevant change in the EDSS performed by the Independent 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 or 2 points on one functional score (excluding changes involving bowel/bladder or cerebral functional system). Comparisons were made to the previous rating (the last EDSS rating that did not occur during a relapse).	Baseline up to 2.5 years
Secondary	3-month Confirmed Disability Worsening (3mCDW) Based on EDSS > 8 Weeks After Onset of Treatment - Pooled Data	A 3-month confirmed disability worsening (3mCDW) was defined as an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 3 months. For patients with a baseline EDSS of 0, the criterion for disability worsening was an increase in EDSS of =1.5, for patients with a baseline EDSS of 1 to 5 or =5.5, the criterion for disability worsening was an increase in EDSS of =1 or =0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2302 to address this endpoint.	Baseline up to 2.5 years
Secondary	6-month Confirmed Disability Worsening (6mCDW) Based on EDSS > 8 Weeks After Onset of Treatment - Pooled Data	A 6-month confirmed disability worsening (6mCDW) was defined as an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 6 months. For patients with a baseline EDSS of 0, the criterion for disability worsening was an increase in EDSS of =1.5, for patients with a baseline EDSS of 1 to 5 or =5.5, the criterion for disability worsening was an increase in EDSS of =1 or =0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2302 to address this endpoint.	Baseline up to 2.5 years
Secondary	6-month Confirmed Cognitive Decline on Symbol Digit Modalities Test (SDMT) - Pooled Data	A 6-month confirmed cognitive decline was defined as a decrease from baseline of at least 4 points in SDMT score sustained for at least 6 months. Processing speed was measured by the Symbol Digit Modalities Test (SDMT) score. SDMT measures the time to pair abstract symbols with specific numbers. The test requires visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items in 90 seconds. (max=110, min=0). Higher scores indicate improvement. Lower scores indicate worsening. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2302 to address this endpoint	Baseline, every 6 months up to 2.5 years
Secondary	6-month Confirmed Disability Worsening (6mCDW) or 6-month Confirmed Cognitive Decline (6mCCD) - Pooled Data	A 6-month confirmed disability worsening (6mCDW) was defined as an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 6 months. For patients with a baseline EDSS of 0, the criterion for disability worsening was an increase in EDSS of =1.5, for patients with a baseline EDSS of 1 to 5 or =5.5, the criterion for disability worsening was an increase in EDSS of =1 or =0.5, respectively. A 6-month confirmed cognitive decline (6mCCD) was defined as a 4-point worsening on Symbol Digit Modalities Test (SDMT) sustained for at least 6 months. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2302 to address this endpoint.	Baseline up to 2.5 years
Secondary	Change in Cognitive Performance Measured by the Symbol Digit Modalities Test (SDMT) - Pooled Data	Processing speed is being measured by the Symbol Digit Modalities Test (SDMT) score. SDMT measures the time to pair abstract symbols with specific numbers. The test requires visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items in 90 seconds. (max=110, min=0). Higher scores indicate improvement. Lower scores indicate worsening.	Baseline up to 2.5 years
Secondary	6-month Confirmed Worsening of at Least 20% in the Timed 25-Foot Walk (T25FW) - Pooled Data	The patient is directed to walk 25 feet quickly and safely as possible from one marked end to the other. The time is calculated from the initiation of the patient instructed to begin, until the patient has reached the 25-foot mark. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2302 to address this endpoint.	Baseline, every 3 months up to 2.5 years
Secondary	6-month Confirmed Worsening of at Least 20% in the 9-Hole Peg Test (9HPT) - Pooled Data	9 Hole Peg Test is a test of upper limb function. Participants place 9 pegs on pegboard and remove pegs and this is timed for each hand. Time recorded in seconds. Longer time indicates poorer upper limb function. 20% improvement is defined as 20% shorter time in seconds. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2302 to address this endpoint.	Baseline, every 6 months up to 2.5 years
Secondary	6-month Confirmed Disability Improvement (6mCDI) Sustained Until End of Study (EOS) as Measured by EDSS - Pooled Data	A 6-month confirmed disability improvement (6mCDI) sustained until EOS was defined as a decrease from baseline EDSS sustained until EOS. For patients with a baseline EDSS of 0 to 1.5, no disability improvement was possible based on the protocol definition of an improvement; for patients with a baseline EDSS of =2 to 6 or =6.5 to 9.5, the criterion for disability improvement was a decrease in EDSS of =1 or =0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2302 to address this endpoint.	Baseline, every 3 months up to 2.5 years
Secondary	Number of New or Enlarging T2 Lesions on MRI Per Year From Month 12 Until End of Study (EOS)	Number of new/enlarging T2 lesions on the last available MRI scan compared to Month 12 adjusted for different time of scans versus Month 12 due to variable follow up time in study.	Month 12 up to 2.5 years
Secondary	Percent Change in T2 Lesion Volume Relative to Baseline	Percent change from baseline in total T2 lesion volume	Baseline, Month 12, Month 24
Secondary	No Evidence of Disease Activity (NEDA-4)	NEDA-4 was defined as no 3-month confirmed disability worsening, no confirmed MS relapse, no new or enlarging T2 lesions compared to baseline, and the annualized rate of brain atrophy >-0.04%.	Baseline, Month 12, Month 24
Secondary	Multiple Sclerosis Impact Scale (MSIS-29) Physical Impact Score Change From Baseline	MSIS-29 is a 29-item, self-administered questionnaire that includes 2 domains, physical and psychological. Responses are captured on a 4-point scale ranging from "not at all" (1) to "extremely" (4), where higher scores reflect greater impact on day to day life.	Baseline, every 6 months up to 2.5 years
Secondary	Multiple Sclerosis Impact Scale (MSIS-29) Psychological Impact Score Change From Baseline	MSIS-29 is a 29-item, self-administered questionnaire that includes 2 domains, physical and psychological. Responses are captured on a 4-point scale ranging from "not at all" (1) to "extremely" (4), where higher scores reflect greater impact on day to day life.	Baseline, every 6 months up to 2.5 years
Secondary	Annualized Relapse Rates (ARR) by NfL High-low Subgroups - Pooled Data	ARR was the number of confirmed relapses in a year, calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of time in study. A confirmed MS relapse was defined as one accompanied by a clinically-relevant change in the EDSS performed by the Independent 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 or 2 points on one functional score (excluding changes involving bowel/bladder or cerebral functional system).	Baseline up to 2.5 years
Secondary	Number of New or Enlarging T2 Lesions Per Year by NfL High-low Subgroups - Pooled Data	Number of new or enlarging T2 lesions on MRI per year (annualized lesion rate).	Baseline, yearly up to 2.5 years
Secondary	Annual Rate of Percent Change in Brain Volume Loss by NfL High-low Subgroups - Pooled Data	Percent change from baseline in brain volume loss (BVL) on all MRI scans adjusted for different time of scan versus baseline due to variable follow up time in study.	Baseline, Months 12 and 24
Secondary	Pharmacokinetic (PK) Concentrations of Ofatumumab	Summary statistics of pharmacokinetic (PK) concentrations from trough samples collected within a 7-day window prior or at day of dosing.	Baseline, Weeks 4, 12, 24, 48, 96