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

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ClinicalTrials.gov Identifier: NCT02792218
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 Sclerosis 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 comparator-controlled, parallel-group, multi-center study with variable treatment duration in approximately 900 patients with relapsing multiple sclorosis (RMS). The maximal treatment duration in the study for an individual patient was 2.5 years.

Eligible patients were randomized to receive either experimental ofatumumab subcutaneous (s.c.) injections every 4 weeks or active comparator teriflunomide orally once daily. The dose regimen for ofatumumab for this study was a loading dose regimen of 20 mg at Day 1, Day 7 and Day 14, followed by a maintenance dose regimen of 20 mg administered every 4 weeks starting at Week 4. In order to blind for the different formulations, double-dummy masking was used i.e. all patients will take injections (containing either active ofatumumab or placebo) and oral capsules (containing either active teriflunomide or placebo).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 930 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 : September 20, 2016
Actual Primary Completion Date : July 5, 2019
Actual Study Completion Date : July 20, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: OMB 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 pre-filled 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 (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.

  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 and 24 ]
    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.

  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): NCT02792218


Locations
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United States, Arizona
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Phoenix, Arizona, United States, 85013
United States, California
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Berkeley, California, United States, 94705
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Fullerton, California, United States, 92835
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Sacramento, California, United States, 95817
United States, District of Columbia
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Washington, District of Columbia, United States, 20007
United States, Florida
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Atlantis, Florida, United States, 33462-6608
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Delray Beach, Florida, United States, 33445
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Hollywood, Florida, United States, 33021
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Loxahatchee Groves, Florida, United States, 33470
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Miami, Florida, United States, 33032
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Miami, Florida, United States, 33136
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Naples, Florida, United States, 34102
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North Palm Beach, Florida, United States, 33408
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Pensacola, Florida, United States, 32514
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Port Charlotte, Florida, United States, 33952
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Sunrise, Florida, United States, 33351
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Vero Beach, Florida, United States, 32960
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West Palm Beach, Florida, United States, 33407
United States, Georgia
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Savannah, Georgia, United States, 31406
United States, Hawaii
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Honolulu, Hawaii, United States, 96817
United States, Illinois
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Chicago, Illinois, United States, 60612
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Northbrook, Illinois, United States, 60062
United States, Indiana
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Indianapolis, Indiana, United States, 46202
United States, Iowa
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Des Moines, Iowa, United States, 50314-2611
United States, Kansas
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Kansas City, Kansas, United States, 66160
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Overland Park, Kansas, United States, 66210
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Alexandria, Louisiana, United States, 71301
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Baton Rouge, Louisiana, United States, 70810
United States, Michigan
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Clinton Township, Michigan, United States, 48035
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Detroit, Michigan, United States, 48201
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Golden Valley, Minnesota, United States, 55422
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Chesterfield, Missouri, United States, 63017
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Ozark, Missouri, United States, 65721
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Saint Louis, Missouri, United States, 63110
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Las Vegas, Nevada, United States, 89106
United States, New York
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Latham, New York, United States, 12110
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Charlotte, North Carolina, United States, 28204
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Raleigh, North Carolina, United States, 27607
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Winston-Salem, North Carolina, United States, 27103
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Winston-Salem, North Carolina, United States, 27157
United States, Ohio
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Cleveland, Ohio, United States, 44195
United States, Oklahoma
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Oklahoma City, Oklahoma, United States, 73104
United States, South Carolina
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Spartanburg, South Carolina, United States, 29303
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Johnson City, Tennessee, United States, 37604
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Knoxville, Tennessee, United States, 37920
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Dallas, Texas, United States, 75246
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El Paso, Texas, United States, 79935
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Houston, Texas, United States, 77074
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Round Rock, Texas, United States, 78681
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San Antonio, Texas, United States, 78229
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San Antonio, Texas, United States, 78258
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Virginia Beach, Virginia, United States, 23456
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Green Bay, Wisconsin, United States, 54311
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Madison, Wisconsin, United States, 53792
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Milwaukee, Wisconsin, United States, 53215
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Neenah, Wisconsin, United States, 54956
Argentina
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Rosario, Santa Fe, Argentina, S2000BZL
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Buenos Aires, Argentina, 1061
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Cordoba, Argentina, X5004CDT
Australia, New South Wales
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New Lambton Heights, New South Wales, Australia, 2305
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St Leonards, New South Wales, Australia, 2065
Belgium
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Brasschaat, Belgium, 2930
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Brugge, Belgium, 8000
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Liege, Belgium, 4000
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Pelt, Belgium, 3900
Bulgaria
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Plovdiv, Bulgaria, 4002
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Sofia, Bulgaria, 1309
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Sofia, Bulgaria, 1431
Canada, British Columbia
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Vancouver, British Columbia, Canada, V6T 1Z3
Canada, Quebec
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Gatineau, Quebec, Canada, J9J 0A5
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Montreal, Quebec, Canada, H3A 2B4
Canada
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Quebec, Canada, G1J 1Z4
Croatia
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Rijeka, HRV, Croatia, 51000
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Zagreb, Croatia, 10000
Czechia
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Praha 4 Krc, Czech Republic, Czechia, 140 59
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Hradec Kralove, CZE, Czechia, 500 05
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Olomouc, CZE, Czechia, 775 20
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JIhlava, Czechia, 586 01
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Pardubice, Czechia, 532 03
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Praha 5, Czechia, 150 06
Denmark
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Aarhus, Denmark, 8000
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Copenhagen, Denmark, DK-2100
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Odense C, Denmark, 5000
Estonia
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Tallinn, Estonia, 10617
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Tartu, Estonia, 51014
France
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Nancy, Cedex, France, 54035
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Lille Cedex, France, 59037
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Nantes Cedex 1, France, 44093
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Nimes Cedex, France, 30029
Germany
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Barsinghausen, Germany, 30890
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Bayreuth, Germany, 95445
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Bielefeld, Germany, D 33647
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Hamburg, Germany, 20249
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Marburg, Germany, 35043
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Muenchen, Germany, 80377
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Muenchen, Germany, 81377
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Neuburg an der Donau, Germany, 86633
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Potsdam, Germany, 14471
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Ulm, Germany, 89073
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Wiesbaden, Germany, 65191
Greece
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Athens, GR, Greece, 115 25
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Athens, Greece, 115 28
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Thessaloniki, Greece, GR 54636
Hungary
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Budapest, HUN, Hungary, 1135
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Budapest, Hungary, 1106
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Kistarcsa, Hungary, 2143
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Szeged, Hungary, 6725
India
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New Delhi, Delhi, India, 110017
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Bangalore, Karnataka, India, 560054
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Kochi, Kerala, India, 682 026
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Chandigarh, Punjab, India, 160012
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Kolkata, West Bengal, India, 700068
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Mangalore, India, 575018
Israel
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Ashkelon, Israel, 78278
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Haifa, Israel, 310 9601
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Sefad, Israel, 13100
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Tel Aviv, Israel, 6423906
Italy
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Milano, MI, Italy, 20132
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Roma, RM, Italy, 00189
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Gallarate, VA, Italy, 21013
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Napoli, Italy, 80131
Mexico
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Mexico, Distrito Federal, Mexico, 03100
Netherlands
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Sittard-Geleen, BG, Netherlands, 6162 BG
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Amsterdam, Netherlands, 1081 HV
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Rotterdam, Netherlands, 3015 CE
Poland
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Bydgoszcz, Poland, 85-796
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Gdansk, Poland, 80 952
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Gdansk, Poland, 80-462
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Gdansk, Poland, 80-803
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Katowice, Poland, 40 571
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Kielce, Poland, 25 726
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Lodz, Poland, 90 324
Puerto Rico
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Guaynabo, Puerto Rico, 00968
Russian Federation
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Kemerovo, Russian Federation, 650066
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Moscow, Russian Federation, 125367
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Nizhny Novgorod, Russian Federation, 603155
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Novosibirsk, Russian Federation, 630007
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Saint Petersburg, Russian Federation, 194044
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Saransk, Russian Federation, 430032
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Sestroretsk, Russian Federation, 197706
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Tyumen, Russian Federation, 625000
Slovakia
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Banska Bystrica, Slovakia, 97517
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Bratislava, Slovakia, 82606
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Bratislava, Slovakia, 83305
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Nitra, Slovakia, 94901
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Trnava, Slovakia, 917 75
Spain
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Cadiz, Andalucia, Spain, 11009
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Barcelona, Cataluna, Spain, 08026
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Barcelona, Cataluna, Spain, 08036
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Barcelona, Catalunya, Spain, 08035
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L Hospitalet De Llobregat, Catalunya, Spain, 08907
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Salt, Cataluña, Spain, 17190
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El Palmar, Murcia, Spain, 30120
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Barcelona, Spain, 08003
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Valencia, Spain, 46026
Sweden
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Goeteborg, Sweden, 413 45
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Stockholm, Sweden, 102 35
Switzerland
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Basel, Switzerland, 4031
Thailand
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Khon Kaen, THA, Thailand, 40002
Turkey
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Istanbul, Turkey, 34147
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Izmir, Turkey, 35040
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Kocaeli, Turkey, 41380
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Samsun, Turkey, 55139
United Kingdom
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Headington, Oxfordshire, United Kingdom, OX3 9DU
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Glasgow, United Kingdom, G51 4TF
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London, United Kingdom, E1 1BB
Sponsors and Collaborators
Novartis Pharmaceuticals
  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: NCT02792218    
Other Study ID Numbers: COMB157G2301
2015-005418-31 ( 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


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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