Efficacy and Safety of Ofatumumab Compared to Teriflunomide in Patients With Relapsing Multiple Sclerosis. (ASCLEPIOS II)

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

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

Study Overview

• Status: Completed
• Conditions: Relapsing Multiple Scelrosis
• Intervention / Treatment: Drug: Ofatumumab subcutaneous injection; Drug: Teriflunomide-matching placebo capsules; Drug: Teriflunomide capsule; Drug: Matching placebo of ofatumumab subcutaneous injections

Detailed 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).

• Study Type: Interventional
• Enrollment (Actual): 955
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Tucuman, Argentina, 4000
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1428AQK
      • Novartis Investigative Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000DSW
      • Novartis Investigative Site
• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Novartis Investigative Site
• Austria
  • Vienna, Austria, 1090
    • Novartis Investigative Site
  • Wien, Austria, 1010
    • Novartis Investigative Site
• Belgium
  • Aalst, Belgium, 9300
    • Novartis Investigative Site
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Gent, Belgium, 9000
    • Novartis Investigative Site
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Novartis Investigative Site
• Bulgaria
  • Sofia, Bulgaria, 1113
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1413
    • Novartis Investigative Site
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • Novartis Investigative Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Novartis Investigative Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Novartis Investigative Site
• Croatia
  • Osijek, Croatia, 31000
    • Novartis Investigative Site
  • Zagreb, Croatia, 10000
    • Novartis Investigative Site
• Czechia
  • Ostrava-Poruba, Czechia, 708 52
    • Novartis Investigative Site
  • Praha 10, Czechia, 100 34
    • Novartis Investigative Site
  • Czech Republic
    • Brno, Czech Republic, Czechia, 656 91
      • Novartis Investigative Site
    • Havirov, Czech Republic, Czechia, 736 01
      • Novartis Investigative Site
    • Teplice, Czech Republic, Czechia, 415 01
      • Novartis Investigative Site
• Finland
  • Tampere, Finland, 33100
    • Novartis Investigative Site
  • Turku, Finland, 20520
    • Novartis Investigative Site
• France
  • Bordeaux Cedex, France, 33076
    • Novartis Investigative Site
  • Clermont-Ferrand, France, 63000
    • Novartis Investigative Site
  • Montpellier, France, 34295
    • Novartis Investigative Site
  • Paris Cedex 13, France, 75651
    • Novartis Investigative Site
  • Rennes Cedex, France, 35033
    • Novartis Investigative Site
  • Strasbourg, France, 67098
    • Novartis Investigative Site
  • Cedex1
    • Nice, Cedex1, France, 06001
      • Novartis Investigative Site
• Germany
  • Bochum, Germany, 44791
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Essen, Germany, 45147
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  • Hamburg, Germany, 22179
    • Novartis Investigative Site
  • Hannover, Germany, 30625
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  • Heidelberg, Germany, 69120
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  • Homburg, Germany, 66421
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  • Koln, Germany, 50935
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  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Leipzig, Germany, 04107
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  • Minden, Germany, 32429
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  • Siegen, Germany, 57076
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  • Ulm, Germany, 89081
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  • Unterhaching, Germany, 82008
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• Hungary
  • HUN
    • Budapest, HUN, Hungary, 1204
      • Novartis Investigative Site
    • Esztergom, HUN, Hungary, 2500
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• India
  • Mumbai, India, 400016
    • Novartis Investigative Site
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500018
      • Novartis Investigative Site
  • Delhi
    • New Delhi, Delhi, India, 110 060
      • Novartis Investigative Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400008
      • Novartis Investigative Site
    • Mumbai, Maharashtra, India, 400012
      • Novartis Investigative Site
    • Pune, Maharashtra, India, 411004
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  • Punjab
    • Ludhiana, Punjab, India, 141008
      • Novartis Investigative Site
• Italy
  • Genova, Italy, 16132
    • Novartis Investigative Site
  • Milano, Italy, 20133
    • Novartis Investigative Site
  • Napoli, Italy, 80138
    • Novartis Investigative Site
  • Rome, Italy, 00178
    • Novartis Investigative Site
  • PD
    • Padova, PD, Italy, 35128
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00133
      • Novartis Investigative Site
• Latvia
  • Riga, Latvia, LV 1002
    • Novartis Investigative Site
  • Riga, Latvia, LV-1038
    • Novartis Investigative Site
  • LV
    • Riga, LV, Latvia, LV-1005
      • Novartis Investigative Site
• Lithuania
  • Vilnius, Lithuania, LT-08661
    • Novartis Investigative Site
  • LTU
    • Kaunas, LTU, Lithuania, LT 50161
      • Novartis Investigative Site
• Mexico
  • Chihuahua, Mexico, 31238
    • Novartis Investigative Site
• Norway
  • Drammen, Norway, 1086
    • Novartis Investigative Site
• Peru
  • Lima, Peru, Lima 13
    • Novartis Investigative Site
  • Lima
    • Cercado De Lima, Lima, Peru, 01
      • Novartis Investigative Site
    • San Isidro, Lima, Peru, 27
      • Novartis Investigative Site
• Poland
  • Glogow, Poland, 36-060
    • Novartis Investigative Site
  • Rzeszow, Poland, 35 055
    • Novartis Investigative Site
  • Warszawa, Poland, 02 957
    • Novartis Investigative Site
  • Wroclaw, Poland, 51-685
    • Novartis Investigative Site
  • Zabrze, Poland, 41-800
    • Novartis Investigative Site
• Portugal
  • Amadora, Portugal, 2720-276
    • Novartis Investigative Site
  • Braga, Portugal, 4710243
    • Novartis Investigative Site
  • Coimbra, Portugal, 3000-075
    • Novartis Investigative Site
  • Lisboa, Portugal, 1500 650
    • Novartis Investigative Site
  • Lisboa, Portugal, 1600190
    • Novartis Investigative Site
  • Lisboa, Portugal, 1169-050
    • Novartis Investigative Site
  • Loures, Portugal, 2674514
    • Novartis Investigative Site
  • Porto, Portugal, 4000001
    • Novartis Investigative Site
  • Santa Maria da Feira, Portugal, 4520 211
    • Novartis Investigative Site
  • Porto
    • Matosinhos, Porto, Portugal, 4454509
      • Novartis Investigative Site
• Russian Federation
  • Ekaterinburg, Russian Federation, 620109
    • Novartis Investigative Site
  • Kazan, Russian Federation, 420021
    • Novartis Investigative Site
  • Krasnoyarsk, Russian Federation, 660049
    • Novartis Investigative Site
  • Moscow, Russian Federation, 127015
    • Novartis Investigative Site
  • Nizhny Novgorod, Russian Federation, 603137
    • Novartis Investigative Site
  • Novosibirsk, Russian Federation, 630087
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 197022
    • Novartis Investigative Site
  • St. Petersburg, Russian Federation, 197376
    • Novartis Investigative Site
  • St. Petersburg, Russian Federation, 197110
    • Novartis Investigative Site
• Slovakia
  • Bratislava, Slovakia, 813 69
    • Novartis Investigative Site
  • Martin, Slovakia, 036 59
    • Novartis Investigative Site
  • Ruzomberok, Slovakia, 03426
    • Novartis Investigative Site
• South Africa
  • Pretoria, South Africa, 0041
    • Novartis Investigative Site
  • Rosebank, South Africa, 2196
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Madrid, Spain, 28006
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Madrid, Spain, 28222
    • Novartis Investigative Site
  • San Sebastian, Spain, 20014
    • Novartis Investigative Site
  • Andalucia
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41017
      • Novartis Investigative Site
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Novartis Investigative Site
  • Vizcaya
    • Baracaldo, Vizcaya, Spain, 48903
      • Novartis Investigative Site
• Switzerland
  • Lugano, Switzerland, 6900
    • Novartis Investigative Site
• Taiwan
  • Tainan, Taiwan, 70403
    • Novartis Investigative Site
• Turkey
  • Haseki / Istanbul, Turkey, 34096
    • Novartis Investigative Site
  • Izmir, Turkey, 35340
    • Novartis Investigative Site
  • Mersin, Turkey, 33079
    • Novartis Investigative Site
  • Trabzon, Turkey, 61080
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom, SW17 0QT
    • Novartis Investigative Site
  • London, United Kingdom, SE5 9RS
    • Novartis Investigative Site
  • Beds
    • Luton, Beds, United Kingdom, LU4 0DZ
      • Novartis Investigative Site
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2JF
      • Novartis Investigative Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233-0271
      • Novartis Investigative Site
    • Cullman, Alabama, United States, 35058
      • Novartis Investigative Site
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Novartis Investigative Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Novartis Investigative Site
    • Basalt, Colorado, United States, 81621
      • Novartis Investigative Site
    • Boulder, Colorado, United States, 80301
      • Novartis Investigative Site
    • Centennial, Colorado, United States, 80112
      • Novartis Investigative Site
    • Colorado Springs, Colorado, United States, 80907
      • Novartis Investigative Site
    • Denver, Colorado, United States, 80210
      • Novartis Investigative Site
    • Fort Collins, Colorado, United States, 80528
      • Novartis Investigative Site
    • Fort Collins, Colorado, United States, 907-280528
      • Novartis Investigative Site
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Novartis Investigative Site
  • Delaware
    • Newark, Delaware, United States, 19713
      • Novartis Investigative Site
  • Florida
    • Bradenton, Florida, United States, 34205
      • Novartis Investigative Site
    • Gainesville, Florida, United States, 32611
      • Novartis Investigative Site
    • Maitland, Florida, United States, 32751
      • Novartis Investigative Site
    • Ocala, Florida, United States, 34471
      • Novartis Investigative Site
    • Oldsmar, Florida, United States, 34677
      • Novartis Investigative Site
    • Ormond Beach, Florida, United States, 32174
      • Novartis Investigative Site
    • Palm Coast, Florida, United States, 32164
      • Novartis Investigative Site
    • Saint Petersburg, Florida, United States, 33713
      • Novartis Investigative Site
    • Sarasota, Florida, United States, 34243
      • Novartis Investigative Site
    • Tallahassee, Florida, United States, 32312
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33612
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33609
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33603
      • Novartis Investigative Site
  • Georgia
    • Suwanee, Georgia, United States, 30024
      • Novartis Investigative Site
  • Indiana
    • Anderson, Indiana, United States, 46011
      • Novartis Investigative Site
    • Indianapolis, Indiana, United States, 46256
      • Novartis Investigative Site
  • Massachusetts
    • Wellesley, Massachusetts, United States, 02481
      • Novartis Investigative Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Novartis Investigative Site
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Novartis Investigative Site
  • Montana
    • Billings, Montana, United States, 59101
      • Novartis Investigative Site
    • Great Falls, Montana, United States, 59405
      • Novartis Investigative Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-0001
      • Novartis Investigative Site
  • North Carolina
    • Asheville, North Carolina, United States, 28806
      • Novartis Investigative Site
    • Charlotte, North Carolina, United States, 28202
      • Novartis Investigative Site
    • Greensboro, North Carolina, United States, 27405
      • Novartis Investigative Site
  • Ohio
    • Akron, Ohio, United States, 44320
      • Novartis Investigative Site
    • Columbus, Ohio, United States, 43214
      • Novartis Investigative Site
    • Columbus, Ohio, United States, 43221
      • Novartis Investigative Site
    • Westerville, Ohio, United States, 43081
      • Novartis Investigative Site
  • Oregon
    • Portland, Oregon, United States, 97225
      • Novartis Investigative Site
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Novartis Investigative Site
    • Willow Grove, Pennsylvania, United States, 19090
      • Novartis Investigative Site
  • South Carolina
    • Greer, South Carolina, United States, 29650
      • Novartis Investigative Site
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Novartis Investigative Site
    • Knoxville, Tennessee, United States, 37922
      • Novartis Investigative Site
    • Nashville, Tennessee, United States, 37205
      • Novartis Investigative Site
  • Texas
    • Greenville, Texas, United States, 75401
      • Novartis Investigative Site
    • Lubbock, Texas, United States, 79410
      • Novartis Investigative Site
    • Sherman, Texas, United States, 75092
      • Novartis Investigative Site
  • Utah
    • Orem, Utah, United States, 84058
      • Novartis Investigative Site
    • Salt Lake City, Utah, United States, 84132
      • Novartis Investigative Site
    • Salt Lake City, Utah, United States, 84103
      • Novartis Investigative Site
  • Washington
    • Kirkland, Washington, United States, 98034
      • Novartis Investigative Site
    • Seattle, Washington, United States, 98122
      • Novartis Investigative Site
    • Tacoma, Washington, United States, 98405
      • Novartis Investigative Site
  • Wisconsin
    • Waukesha, Wisconsin, United States, 53188
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OMG 20 mg; Ofatumumab 20 mg pre-filled syringes for subcutaneous injectionon on days 1 ,7 ,14, week 4 and every 4 weeks thereafter and a teriflunomide-matching placebo, taken orally once daily	Drug: Ofatumumab subcutaneous injection; Ofatumumab 20 mg prefilled syringes for subcutaneous injection on days 1, 7, 14, week 4 and every 4 weeks thereafter; Drug: Teriflunomide-matching placebo capsules; Placebo capsule, matching in appearance to teriflunomide, taken orally once daily
Active Comparator: TER 14 mg; Teriflunomide 14 mg oral capsule taken once daily and matching placebo for subcutaneous injections to ofatumumab on days 1, 7, 14, week 4 and every 4 weeks thereafter	Drug: Teriflunomide capsule; Teriflunomide 14 mg oral capsule taken once daily; Drug: Matching placebo of ofatumumab subcutaneous injections; Matching placebo of ofatumumab subcutaneous injections on days 1, 7, 14, week 4 and every 4 weeks thereafter

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Percent Change in T2 Lesion Volume Relative to Baseline	Percent change from baseline in total T2 lesion volume	Baseline, Month 12, Month 24
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Gartner J, Hauser SL, Bar-Or A, Montalban X, Cohen JA, Cross AH, Deiva K, Ganjgahi H, Haring DA, Li B, Pingili R, Ramanathan K, Su W, Willi R, Kieseier B, Kappos L. Efficacy and safety of ofatumumab in recently diagnosed, treatment-naive patients with multiple sclerosis: Results from ASCLEPIOS I and II. Mult Scler. 2022 Sep;28(10):1562-1575. doi: 10.1177/13524585221078825. Epub 2022 Mar 10.
• Hauser SL, Bar-Or A, Cohen JA, Comi G, Correale J, Coyle PK, Cross AH, de Seze J, Leppert D, Montalban X, Selmaj K, Wiendl H, Kerloeguen C, Willi R, Li B, Kakarieka A, Tomic D, Goodyear A, Pingili R, Haring DA, Ramanathan K, Merschhemke M, Kappos L; ASCLEPIOS I and ASCLEPIOS II Trial Groups. Ofatumumab versus Teriflunomide in Multiple Sclerosis. N Engl J Med. 2020 Aug 6;383(6):546-557. doi: 10.1056/NEJMoa1917246.

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2016
• Primary Completion (Actual): July 10, 2019
• Study Completion (Actual): October 22, 2020

Study Registration Dates

• First Submitted: June 2, 2016
• First Submitted That Met QC Criteria: June 2, 2016
• First Posted (Estimate): June 7, 2016

Study Record Updates

• Last Update Posted (Actual): November 22, 2021
• Last Update Submitted That Met QC Criteria: October 21, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: adult; Ofatumumab; OMB157; RRMS; relapse; Relapsing multiple sclerosis; multiple sclerosis; SPMS; T2 lesions; T1 lesions; GD-enhancing MRI; McDonald criteria
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Ofatumumab; Antibodies, Monoclonal; Teriflunomide
• Other Study ID Numbers: COMB157G2302; 2015-005419-33 (EudraCT Number)

Plan for Individual participant data (IPD)

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

IPD Plan Description

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

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No