Long-term Safety, Tolerability and Effectiveness Study of Ofatumumab in Patients With Relapsing MS

Relapsing Multiple Sclerosis Clinical Trial

— ALITHIOS  

Official title:

An Open-label, Single Arm, Multi-center Extension Study Evaluating Long-term Safety, Tolerability and Effectiveness of Ofatumumab in Subjects With Relapsing Multiple Sclerosis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03650114
• Other study ID #: COMB157G2399
• Status: Recruiting
• Phase: Phase 3
• Start date: December 28, 2018
• Est. completion date: September 7, 2028

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: Novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to collect long-term safety, tolerability, effectiveness and health outcomes data in eligible subjects who have participated in a Novartis ofatumumab clinical MS study.

Vaccination sub-study The purpose of this research sub-study is to find out the effects of ofatumumab on the development of antibody responses to selected vaccines and keyhole limpet hemocyanin (KLH) neo-antigen in subjects with relapsing multiple sclerosis (RMS).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2060
• Est. completion date: September 7, 2028
• Est. primary completion date: December 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

1. Must have completed a selected Novartis MS study which dosed ofatumumab 20 mg sc every 4 weeks

2. Written informed consent

Exclusion Criteria:

• Emergence of any clinically significant condition/disease during the previous ofatumumab study in which study participation might result in safety risk for the subject

• Subjects with active systemic bacterial, viral or fingal infections, or chronic infection (e.g. AIDS)

• Subjects taking medications prohibited by the protocol

• Pregnant or nursing (lactating) women Other protocol-defined inclusion/exclusion criteria may apply

Vaccination sub-study:

Inclusion criteria

1. Informed consent

2. Actively enrolled in the COMB157G2399 Study

3. 12 weeks of continuous treatment within the COMB157G2399 Study

4. prior vaccination history as per protocol-defined

Exclusion criteria

• known hypersensitivity or history of systemic allergic, neurologic or other reactions to vaccines

• allergies to egg or shellfish

• any safety findings including low IgG/IgM requiring ofatumumab interruption within 12 weeks prior to vaccination sub-study start

• any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 2 weeks of the first vaccination sub-study visit

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

• Multiple Sclerosis
• Relapsing Multiple Sclerosis
• Sclerosis

Intervention

Biological:
• Ofatumumab
subcutaneous injection of 20 mg ofatumumab every 4 weeks
• Tetanus toxoid (TT) containing vaccine (Td, Tdap)
0.5mL Vial/Syringe Containing 5 limit of flocculation (LF) tetanus toxoid
• 13-valent pneumococcal conjugate vaccine (13-PCV)
0.5mL Vial/Syringe
• 23-valent pneumococcal polysaccharide vaccine (23-PPV)
0.5mL Vial/Syringe
• Seasonal Quadrivalent influenza vaccine
Seasonal 2020-2021 0.5mL Vial/Syringe (trivalent may be used where quadrivalent is not available)
• Keyhole limpet hemocyanin (KLH) neo-antigen
1mg Vial

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Tucuman
Australia	Novartis Investigative Site	Liverpool	New South Wales
Australia	Novartis Investigative Site	New Lambton Heights	New South Wales
Australia	Novartis Investigative Site	St Leonards	New South Wales
Austria	Novartis Investigative Site	Vienna
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Brasschaat
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Edegem	Antwerpen
Belgium	Novartis Investigative Site	Gent
Bulgaria	Novartis Investigative Site	Pleven
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Canada	Novartis Investigative Site	Gatineau	Quebec
Canada	Novartis Investigative Site	Greenfield Park	Quebec
Canada	Novartis Investigative Site	London	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Croatia	Novartis Investigative Site	Osijek
Croatia	Novartis Investigative Site	Rijeka	HRV
Croatia	Novartis Investigative Site	Zagreb
Czechia	Novartis Investigative Site	Brno	Czech Republic
Czechia	Novartis Investigative Site	Havirov	Czech Republic
Czechia	Novartis Investigative Site	Hradec Kralove	CZE
Czechia	Novartis Investigative Site	JIhlava
Czechia	Novartis Investigative Site	Olomouc	CZE
Czechia	Novartis Investigative Site	Ostrava Poruba
Czechia	Novartis Investigative Site	Pardubice
Czechia	Novartis Investigative Site	Praha 10
Czechia	Novartis Investigative Site	Praha 4
Czechia	Novartis Investigative Site	Praha 5
Czechia	Novartis Investigative Site	Teplice	Czech Republic
Denmark	Novartis Investigative Site	Copenhagen
Denmark	Novartis Investigative Site	Odense C
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
Finland	Novartis Investigative Site	Tampere
Finland	Novartis Investigative Site	Turku
France	Novartis Investigative Site	Lille
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Nice	Cedex1
France	Novartis Investigative Site	Nimes
France	Novartis Investigative Site	Paris 13
France	Novartis Investigative Site	Strasbourg
Germany	Novartis Investigative Site	Barsinghausen
Germany	Novartis Investigative Site	Bayreuth
Germany	Novartis Investigative Site	Bielefeld
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	Koln
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Minden
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	Siegen
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Unterhaching
Greece	Novartis Investigative Site	Athens	GR
Greece	Novartis Investigative Site	Thessaloniki
Hungary	Novartis Investigative Site	Budapest	HUN
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Kistarcsa
Hungary	Novartis Investigative Site	Pecs
Hungary	Novartis Investigative Site	Szeged
India	Novartis Investigative Site	Chandigarh	Punjab
India	Novartis Investigative Site	Howrah	West Bengal
India	Novartis Investigative Site	Hyderabad	Telangana
India	Novartis Investigative Site	Kochi	Kerala
India	Novartis Investigative Site	Mangalore
India	Novartis Investigative Site	Mumbai	Maharashtra
India	Novartis Investigative Site	New Delhi	Delhi
India	Novartis Investigative Site	New Delhi	Delhi
India	Novartis Investigative Site	Pune	Maharashtra
Israel	Novartis Investigative Site	Ashkelon
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Sefad
Israel	Novartis Investigative Site	Tel Aviv
Japan	Novartis Investigative Site	Chiba
Japan	Novartis Investigative Site	Kawagoe	Saitama
Japan	Novartis Investigative Site	Kodaira	Tokyo
Japan	Novartis Investigative Site	Morioka	Iwate
Japan	Novartis Investigative Site	Niigata
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Sapporo city	Hokkaido
Japan	Novartis Investigative Site	Sendai city	Miyagi
Japan	Novartis Investigative Site	Sendai city	Miyagi
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Toon city	Ehime
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
Mexico	Novartis Investigative Site	Ciudad de Mexico	Distrito Federal
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Mexico	Novartis Investigative Site	Morelia	Michoacan
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Sittard-Geleen
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	Bydgoszcz	Woj Kujawsko-pomorskie
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Gdansk
Poland	Novartis Investigative Site	Glogow
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Kielce
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Rzeszow
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Wroclaw
Poland	Novartis Investigative Site	Zabrze
Portugal	Novartis Investigative Site	Braga
Portugal	Novartis Investigative Site	Coimbra
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	Kemerovo
Russian Federation	Novartis Investigative Site	Krasnoyarsk
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Nizhny Novgorod
Russian Federation	Novartis Investigative Site	Nizhny Novgorod
Russian Federation	Novartis Investigative Site	Novosibirsk
Russian Federation	Novartis Investigative Site	Novosibirsk
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saransk
Russian Federation	Novartis Investigative Site	Sestroretsk
Russian Federation	Novartis Investigative Site	St Petersburg
Russian Federation	Novartis Investigative Site	St. Petersburg
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	Bratislava
Slovakia	Novartis Investigative Site	Martin
Slovakia	Novartis Investigative Site	Nitra
Slovakia	Novartis Investigative Site	Trnava
South Africa	Novartis Investigative Site	Pretoria
South Africa	Novartis Investigative Site	Rosebank
Spain	Novartis Investigative Site	Baracaldo	Vizcaya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Cadiz	Andalucia
Spain	Novartis Investigative Site	Castilleja De La Cuesta	Sevilla
Spain	Novartis Investigative Site	El Palmar	Murcia
Spain	Novartis Investigative Site	Hospitalet de Llobregat	Barcelona
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	Salt	Cataluna
Spain	Novartis Investigative Site	San Sebastian	Pais Vasco
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia
Sweden	Novartis Investigative Site	Goeteborg
Sweden	Novartis Investigative Site	Stockholm
Switzerland	Novartis Investigative Site	Basel
Switzerland	Novartis Investigative Site	Lugano
Taiwan	Novartis Investigative Site	Tainan
Thailand	Novartis Investigative Site	Khon Kaen	THA
Turkey	Novartis Investigative Site	Haseki Istanbul
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Istanbul	TUR
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Kocaeli
Turkey	Novartis Investigative Site	Mersin
Turkey	Novartis Investigative Site	Samsun
Turkey	Novartis Investigative Site	Sancaktepe	Istanbul
Turkey	Novartis Investigative Site	Trabzon
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Headington	Oxfordshire
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	Neurology and Neuroscience Assos	Akron	Ohio
United States	University of New Mexico	Albuquerque	New Mexico
United States	Neuro Medical Clinic of Cenla LLC COMB157G2301	Alexandria	Louisiana
United States	Asheville Neurology Specialists PA	Asheville	North Carolina
United States	Jem Research Institute	Atlantis	Florida
United States	CU Anschutz Med Campus	Aurora	Colorado
United States	Mountain Neuro Research Center PC .	Basalt	Colorado
United States	The Neuromedical Center	Baton Rouge	Louisiana
United States	Billings Clinic	Billings	Montana
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Alpine Clinical Research Center	Boulder	Colorado
United States	Bradenton Research Center inc	Bradenton	Florida
United States	The Neurological Institute PA	Charlotte	North Carolina
United States	Rush University Medical Center	Chicago	Illinois
United States	Cleveland Clinic Foundation .	Cleveland	Ohio
United States	Colorado Springs Neurological Associates .	Colorado Springs	Colorado
United States	Ohio Health Research Institute	Columbus	Ohio
United States	Wesley Neurology Clinic	Cordova	Tennessee
United States	North Cntrl Neurology Associates PC	Cullman	Alabama
United States	Neurology Offices of South Florida PLLC CBAF312A2304	Delray Beach	Florida
United States	Novartis Investigative Site	Denver	Colorado
United States	Mercy Ruan Neurology Clinic Res Ct.	Des Moines	Iowa
United States	Henry Ford Hospital Main Centre	Detroit	Michigan
United States	Wayne Stat Uni Multi Sclerosis Clnc	Detroit	Michigan
United States	Med Research Inc	El Paso	Texas
United States	Novartis Investigative Site	Fort Collins	Colorado
United States	University of Colorado Health Neuro	Fort Collins	Colorado
United States	Fullerton Neuro and Headache Ctr	Fullerton	California
United States	Advanced Neurology Specialists	Great Falls	Montana
United States	Aurora BayCare Medical Center	Green Bay	Wisconsin
United States	Novartis Investigative Site	Greensboro	North Carolina
United States	Premier Neurology	Greenville	South Carolina
United States	Infinity Clinical Research LLC	Hollywood	Florida
United States	Hawaii Pacific Neuroscience LLC	Honolulu	Hawaii
United States	Novartis Investigative Site	Houston	Texas
United States	Josephson Wallack Munshower Neurology P.C	Indianapolis	Indiana
United States	Tri State Mountain Neurology	Johnson	Tennessee
United States	University of Kansas Medical Center .	Kansas City	Kansas
United States	Evergreen Health Multiple Sclerosis Center	Kirkland	Washington
United States	Hope Neurology	Knoxville	Tennessee
United States	University of Tennessee Medical Center COMB157G2301	Knoxville	Tennessee
United States	Cleveland Clinic Foundation	Las Vegas	Nevada
United States	Ms Ctr Of Northeastern Ny	Latham	New York
United States	Neurology and Sleep Center	Lubbock	Texas
United States	University of Wisconsin Madison	Madison	Wisconsin
United States	Neurology Associates, PA	Maitland	Florida
United States	Homestead Associates in Research Inc	Miami	Florida
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Ascension St Francis Center	Milwaukee	Wisconsin
United States	St Luke s Medical Center Aurora COMB157G2301	Milwaukee	Wisconsin
United States	Aqualane Clinical Research	Naples	Florida
United States	Christiana Care Health Services	Newark	Delaware
United States	Consultants in Neurology	Northbrook	Illinois
United States	Multiple Sclerosis Center of Excellence of OMRF	Oklahoma City	Oklahoma
United States	MS and Neuromuscular Center of Excellence	Oldsmar	Florida
United States	Neurology Associates of Ormond Beach	Ormond Beach	Florida
United States	College Park Family Care Center	Overland Park	Kansas
United States	Sharlin Health and Neurology .	Ozark	Missouri
United States	Emerald Coast Neurology	Pensacola	Florida
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	Barrow Neurological Clinics at St Josephs Hospital and MC	Phoenix	Arizona
United States	Minnesota Center Multiple Sclerosis Main Centre	Plymouth	Minnesota
United States	Neurostudies Inc	Port Charlotte	Florida
United States	Providence Neurological Services West	Portland	Oregon
United States	Velocity Clinical Research	Raleigh	North Carolina
United States	Novartis Investigative Site	Round Rock	Texas
United States	University of California Davis	Sacramento	California
United States	Mercy Research	Saint Louis	Missouri
United States	WA Uni School Of Med	Saint Louis	Missouri
United States	Novartis Investigative Site	Salt Lake City	Utah
United States	The University of Utah	Salt Lake City	Utah
United States	Neurology Center of San Antonio P.A.	San Antonio	Texas
United States	Negroski Neurology	Sarasota	Florida
United States	Roskamp Institute, Inc.	Sarasota	Florida
United States	Velocity Clinical Research	Savannah	Georgia
United States	Texas Institute for Neurological Disorders	Sherman	Texas
United States	Novartis Investigative Site	Spartanburg	South Carolina
United States	Upstate Clinical Trials LLC	Spartanburg	South Carolina
United States	Georgia Neurology and Sleep Medicine Assoc	Suwanee	Georgia
United States	Novartis Investigative Site	Tacoma	Washington
United States	AMO Corporation	Tallahassee	Florida
United States	Axiom Clinical Research of Florida	Tampa	Florida
United States	Clinical Research Of West FL Inc	Tampa	Florida
United States	University Of South Florida	Tampa	Florida
United States	Sentara Neuroscience Institute	Virginia Beach	Virginia
United States	Novartis Investigative Site	Washington	District of Columbia
United States	Dragonfly Research LLC	Wellesley	Massachusetts
United States	Premiere Research Institute	West Palm Beach	Florida
United States	Columbus Neuroscience	Westerville	Ohio
United States	Novartis Investigative Site	Willow Grove	Pennsylvania
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,  Austria,  Belgium,  Bulgaria,  Canada,  Croatia,  Czechia,  Denmark,  Estonia,  Finland,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Japan,  Latvia,  Lithuania,  Mexico,  Netherlands,  Norway,  Peru,  Poland,  Portugal,  Russian Federation,  Slovakia,  South Africa,  Spain,  Sweden,  Switzerland,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Hummoral immune response to TT vaccine	Proportion of subjects with a positive antibody response to TT vaccine measured 4 and 8 weeks after vaccination while treated with ofatumumab; 2-fold increase in titer level; Tetanus anti-bodies = 0.2 IU/mL; Mean titers of anti-tetanus antibody	Pre-vaccination, 4 and 8 weeks post-vaccination
Other	Hummoral immune response to 13-valent pneumococcal conjugate vaccine (13-PCV)	Proportion of subjects with a positive antibody response against individual anti-pneumococcal antibody serotypes while treated with ofatumumab; 2-fold increase in titer level or a > 1 microgram/mL rise in titer compared with pre-immunization titer; Positive anti-body response against at least 2 of the 13 pneumococcal antibody serotypes; Positive anti-body response against at least 50% of serotypes; Mean titers of anti-pneumococcal antibody	4 and 8 weeks
Other	Hummoral immune response to 13-PCV boosted eight weeks later by 23-valent pneumococcal polysaccharide vaccine (23-PPV)	Proportion of subjects with a positive antibody response against individual anti-pneumococcal antibody serotypes (23 serotypes to be tested individually) measured 4 and 8 weeks after the booster 23-PPV while the subject continues to be treated with ofatumumab; 2-fold increase in titer level or a > 1 microgram/mL rise in titer compared with pre-immunization titer; Positive anti-body response against at least 2 of the 23 pneumococcal antibody serotypes; Positive anti-body response against at least 50% of serotypes; Mean titers of anti-pneumococcal antibody	Pre-vaccination, 4 and 8 weeks post-vaccination
Other	Humoral immune response to KLH neo-antigen	Mean titers of anti-KLH antibody measured immediately prior the first administration of KLH and measured immediately prior to the first administration, 4, 8 and 12 weeks after the first administration, and measured 4 weeks post last administration of KLH	Pre-administration, 4, 8, 12 weeks after initial administration and 4 weeks after last administration
Other	Hummoral immune response to 2020-2021 seasonal quadrivalent influenza vaccine	Proportion of subjects fulfilling: Seroconversion: The pre-vaccination HI antibody titer is < 1:10 and the postvaccination measurement is = 1:40 (this applies to subjects with a pre-vaccination HI titer < 1:10), or; Significant increase in HI antibody titer: The pre-vaccination HI antibody titer is = 1:10 and the increase from the pre- to the post-vaccination measurement is = 4-fold (this applies to subjects with a pre-vaccination HI titer = 1:10)	Pre-vaccination and 4 weeks post-vaccination
Other	Antibody response rate to TT and influenza vaccination as a function of exposure to ofatumumab	Immune response to TT and influenza vaccination	8 weeks
Primary	Number of patients that experience an adverse event or abnormal laboratory, vital and/or ECG results and positive suicidiality outcomes		Up to 5 years
Secondary	Number of relapse rates per year	Annual Relapse Rate (ARR) time calculated as number of confirmed relapses divided by time in study per year and will also be presented for the entire duration	Core studies up to 5 years from first dose of ofatumumab (depending on if first dose was in the core or in this extension study or comparator randomization)
Secondary	Patients with confirmed 3 and 6 month disability worsening	A confirmed disability worsening is an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at last 3, or 6 months EDSS consists of seven functional systems and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, and Cerebral functions (Fatigue contributes).	Duration of the study, approximately 5 years
Secondary	Patients with confirmed 6, 12 and 24 month disability improvement and improvement until end of study	Confirmed disability improvement is a decrease from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 6, 12 or 24 months EDSS consists of seven functional systems and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, and Cerebral functions (Fatigue contributes).	Duration of the study, approximately 5 years
Secondary	Patients with changes in Expanded Disability Status Scale (EDSS) scores	Score changes in Expanded Disability Status Scale (EDSS) over time EDSS consists of seven functional systems and an ambulation score that are then combined to determine the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, and Cerebral functions (Fatigue contributes).	Core studies up to 5 years from first dose of ofatumumab (depending on if first dose was in the core or in this extension study or comparator randomization)
Secondary	Changes in and time to 6 month confirmed worsening of Symbol Digit Modalities Test Scores	Score changes and confirmed 4-point worsening sustained for 6 months in Symbol Digit Modalities Test (SDMT) scores The Symbol Digit Modalities Test is a neuropsychological, timed test for sustained attention and concentration. 3 versions will be used, alternating at each visit where done. The number of correct responses will be counted for the score.	Duration of the study, approximately 5 years
Secondary	Changes in the Magnetic Resonance Image (MRI) related to brain volume loss	Percent change from baseline in brain volume loss (BVL)	Core studies up to 5 years from first dose of ofatumumab (depending on if first dose was in the core or in this extension study or comparator randomization)
Secondary	Changes in the Magnetic Resonance Image (MRI) related to T2 lesions	Number of new or enlarging T2 lesions	Core studies up to 5 years from first dose of ofatumumab (depending on if first dose was in the core or in this extension study or comparator randomization)
Secondary	Changes in the Magnetic Resonance Image (MRI) related to Gd-enhancing lesions	Total number of Gd-enhancing lesions on all MRI scans adjusted for different time of scan versus follow up time in study	Core studies up to 5 years from first dose of ofatumumab (depending on if first dose was in the core or in this extension study or comparator randomization)
Secondary	Changes in neurofilament light change serum concentration	Extent of neurofilament light change concentration in blood NfL is a component of the neuronal cytoskeleton and is released into the cerebrospinal fluid and into subsequently blood following neuro-axonal damage	Core studies up to 5 years from first dose of ofatumumab (depending on if first dose was in the core or in this extension study or comparator randomization)