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

Relapsing Multiple Scelrosis Clinical Trial

— ASCLEPIOS II  

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: NCT02792231
• Other study ID #: COMB157G2302
• Secondary ID: 2015-005419-33
• Status: Completed
• Phase: Phase 3
• Start date: August 26, 2016
• Est. completion date: October 22, 2020

Study information

• Verified date: October 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 comparatorcontrolled, 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: 955
• Est. completion date: October 22, 2020
• Est. primary completion date: July 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Male or female patients aged 18 to 55 years at Screening
• Diagnosis of multiple sclerosis (MS)
• Relapsing MS: relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) with disease activity
• Documentation of at least: 1 relapse during the previous 1 year OR 2 relapses during the previous 2 years OR a positive gadolinium-enhancing MRI scan during the year prior to randomization
• Disability status at Screening with an Expanded Disability Status Scale (EDSS) score of 0 to 5.5
• Neurologically stable within 1 month prior to randomization

Exclusion Criteria:

• Patients with primary progressive MS or SPMS without disease activity
• 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 Scelrosis
• Sclerosis

Intervention

Drug:
• Ofatumumab subcutaneous injection
Ofatumumab 20 mg prefilled 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	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Tucuman
Australia	Novartis Investigative Site	Liverpool	New South Wales
Austria	Novartis Investigative Site	Vienna
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Aalst
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Edegem	Antwerpen
Belgium	Novartis Investigative Site	Gent
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Canada	Novartis Investigative Site	Greenfield Park	Quebec
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Croatia	Novartis Investigative Site	Osijek
Croatia	Novartis Investigative Site	Zagreb
Czechia	Novartis Investigative Site	Brno	Czech Republic
Czechia	Novartis Investigative Site	Havirov	Czech Republic
Czechia	Novartis Investigative Site	Ostrava-Poruba
Czechia	Novartis Investigative Site	Praha 10
Czechia	Novartis Investigative Site	Teplice	Czech Republic
Finland	Novartis Investigative Site	Tampere
Finland	Novartis Investigative Site	Turku
France	Novartis Investigative Site	Bordeaux Cedex
France	Novartis Investigative Site	Clermont-Ferrand
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Nice	Cedex1
France	Novartis Investigative Site	Paris Cedex 13
France	Novartis Investigative Site	Rennes Cedex
France	Novartis Investigative Site	Strasbourg
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Homburg
Germany	Novartis Investigative Site	Koln
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Minden
Germany	Novartis Investigative Site	Siegen
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Unterhaching
Hungary	Novartis Investigative Site	Budapest	HUN
Hungary	Novartis Investigative Site	Esztergom	HUN
India	Novartis Investigative Site	Hyderabad	Andhra Pradesh
India	Novartis Investigative Site	Ludhiana	Punjab
India	Novartis Investigative Site	Mumbai
India	Novartis Investigative Site	Mumbai	Maharashtra
India	Novartis Investigative Site	Mumbai	Maharashtra
India	Novartis Investigative Site	New Delhi	Delhi
India	Novartis Investigative Site	Pune	Maharashtra
Italy	Novartis Investigative Site	Genova
Italy	Novartis Investigative Site	Milano
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Rome
Latvia	Novartis Investigative Site	Riga	LV
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Riga
Lithuania	Novartis Investigative Site	Kaunas	LTU
Lithuania	Novartis Investigative Site	Vilnius
Mexico	Novartis Investigative Site	Chihuahua
Norway	Novartis Investigative Site	Drammen
Peru	Novartis Investigative Site	Cercado De Lima	Lima
Peru	Novartis Investigative Site	Lima
Peru	Novartis Investigative Site	San Isidro	Lima
Poland	Novartis Investigative Site	Glogow
Poland	Novartis Investigative Site	Rzeszow
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Poland	Novartis Investigative Site	Zabrze
Portugal	Novartis Investigative Site	Amadora
Portugal	Novartis Investigative Site	Braga
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Loures
Portugal	Novartis Investigative Site	Matosinhos	Porto
Portugal	Novartis Investigative Site	Porto
Portugal	Novartis Investigative Site	Santa Maria da Feira
Russian Federation	Novartis Investigative Site	Ekaterinburg
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Krasnoyarsk
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	St. Petersburg
Russian Federation	Novartis Investigative Site	St. Petersburg
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Martin
Slovakia	Novartis Investigative Site	Ruzomberok
South Africa	Novartis Investigative Site	Pretoria
South Africa	Novartis Investigative Site	Rosebank
Spain	Novartis Investigative Site	Baracaldo	Vizcaya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Pozuelo de Alarcon	Madrid
Spain	Novartis Investigative Site	San Sebastian
Spain	Novartis Investigative Site	Sevilla	Andalucia
Switzerland	Novartis Investigative Site	Lugano
Taiwan	Novartis Investigative Site	Tainan
Turkey	Novartis Investigative Site	Haseki / Istanbul
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Mersin
Turkey	Novartis Investigative Site	Trabzon
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Luton	Beds
United Kingdom	Novartis Investigative Site	Sheffield	South Yorkshire
United States	Novartis Investigative Site	Akron	Ohio
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Anderson	Indiana
United States	Novartis Investigative Site	Asheville	North Carolina
United States	Novartis Investigative Site	Aurora	Colorado
United States	Novartis Investigative Site	Basalt	Colorado
United States	Novartis Investigative Site	Billings	Montana
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Boulder	Colorado
United States	Novartis Investigative Site	Bradenton	Florida
United States	Novartis Investigative Site	Centennial	Colorado
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Cordova	Tennessee
United States	Novartis Investigative Site	Cullman	Alabama
United States	Novartis Investigative Site	Denver	Colorado
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Fairfield	Connecticut
United States	Novartis Investigative Site	Fort Collins	Colorado
United States	Novartis Investigative Site	Fort Collins	Colorado
United States	Novartis Investigative Site	Gainesville	Florida
United States	Novartis Investigative Site	Golden Valley	Minnesota
United States	Novartis Investigative Site	Great Falls	Montana
United States	Novartis Investigative Site	Greensboro	North Carolina
United States	Novartis Investigative Site	Greenville	Texas
United States	Novartis Investigative Site	Greer	South Carolina
United States	Novartis Investigative Site	Indianapolis	Indiana
United States	Novartis Investigative Site	Kirkland	Washington
United States	Novartis Investigative Site	Knoxville	Tennessee
United States	Novartis Investigative Site	Lubbock	Texas
United States	Novartis Investigative Site	Maitland	Florida
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	Newark	Delaware
United States	Novartis Investigative Site	Ocala	Florida
United States	Novartis Investigative Site	Oldsmar	Florida
United States	Novartis Investigative Site	Orem	Utah
United States	Novartis Investigative Site	Ormond Beach	Florida
United States	Novartis Investigative Site	Palm Coast	Florida
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Saint Petersburg	Florida
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	Novartis Investigative Site	Sarasota	Florida
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Sherman	Texas
United States	Novartis Investigative Site	Suwanee	Georgia
United States	Novartis Investigative Site	Tacoma	Washington
United States	Novartis Investigative Site	Tallahassee	Florida
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Tucson	Arizona
United States	Novartis Investigative Site	Waukesha	Wisconsin
United States	Novartis Investigative Site	Wellesley	Massachusetts
United States	Novartis Investigative Site	Westerville	Ohio
United States	Novartis Investigative Site	Willow Grove	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  Croatia,  Czechia,  Finland,  France,  Germany,  Hungary,  India,  Italy,  Latvia,  Lithuania,  Mexico,  Norway,  Peru,  Poland,  Portugal,  Russian Federation,  Slovakia,  South Africa,  Spain,  Switzerland,  Taiwan,  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 COMB157G2301 to address this endpoint.	Baseline, every 3 months up to 2.5 years
Secondary	3-month Confirmed Disability Worsening (3mCDW) Based on EDSS - Study COMB157G2302	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 COMB157G2301 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 COMB157G2301 to address this endpoint.	Baseline, every 3 months up to 2.5 years
Secondary	6-month Confirmed Disability Worsening (6mCDW) Based on EDSS - Study COMB157G2302	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 COMB157G2301 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 COMB157G2301 to address this endpoint.	Baseline, every 3 months up to 2.5 years
Secondary	6-month Confirmed Disability Improvement (6mCDI ) Based on EDSS - Study COMB157G2302	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 COMB157G2301 to address this endpoint.	Baseline, every 3 months up to 2.5 years
Secondary	Number of Gadolinium-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	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 COMB157G2301 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 COMB157G2301 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 COMB157G2301 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 COMB157G2301 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. 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 COMB157G2301 to address this endpoint.	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 COMB157G2301 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 COMB157G2301 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 COMB157G2301 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	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