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

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ClinicalTrials.gov Identifier: NCT02792231
Recruitment Status : Completed
First Posted : June 7, 2016
Results First Posted : October 19, 2020
Last Update Posted : May 12, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief 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

Condition or disease Intervention/treatment Phase
Relapsing Multiple Scelrosis Drug: Ofatumumab subcutaneous injection Drug: Teriflunomide-matching placebo capsules Drug: Teriflunomide capsule Drug: Matching placebo of ofatumumab subcutaneous injections Phase 3

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 957 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.
Actual Study Start Date : August 26, 2016
Actual Primary Completion Date : July 10, 2019
Actual Study Completion Date : October 22, 2020

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Annualized Relapse Rate (ARR) (Confirmed Relapses) [ Time Frame: Baseline up to 2.5 years ]
    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).


Secondary Outcome Measures :
  1. 3-month Confirmed Disability Worsening) (3mCDW) Based on EDSS [ Time Frame: Baseline, every 3 months up to 2.5 years ]
    A 3-month confirmed disability worsening is an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at last 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

  2. 6-month Confirmed Disability Worsening (6mCDW) Based on EDSS [ Time Frame: Baseline, every 3 months up to 2.5 years ]
    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.

  3. 6-month Confirmed Disability Improvement) (6mCDI ) Based on EDSS [ Time Frame: Baseline, every 3 months up to 2.5 years ]
    A 6-month confirmed disability improvement is a decrease from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 6 months.

  4. Number of Gd-enhancing T1 Lesions Per MRI Scan [ Time Frame: Baseline, yearly up to 2.5 years ]
    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

  5. Number of New or Enlarging T2 Lesions on MRI Per Year (Annualized Lesion Rate) [ Time Frame: Baseline, yearly up to 2.5 years ]
    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

  6. Neurofilament Light Chain (NfL) Concentration in Serum [ Time Frame: Month 3, 12, 24 ]
    The NfL concentration (geometric mean concentration) will be estimated by treatment and time point with using a repeated measures model on the basis of all evaluable log-transformed NfL values.

  7. Annualized Rate of Brain Volume Loss Based on Assessments of Percent Brain Volume Change From Baseline [ Time Frame: Baseline, months 12 and 24 ]
    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



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02792231


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

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] August 6, 2018
Statistical Analysis Plan  [PDF] October 17, 2019

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02792231    
Other Study ID Numbers: COMB157G2302
2015-005419-33 ( EudraCT Number )
First Posted: June 7, 2016    Key Record Dates
Results First Posted: October 19, 2020
Last Update Posted: May 12, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Relapsing multiple sclerosis
Ofatumumab
adult
OMB157
multiple sclerosis
T1 lesions
T2 lesions
relapse
GD-enhancing MRI
McDonald criteria
RRMS
SPMS
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Ofatumumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs