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

NCT02792231 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: COMB157G23022015-005419-33
• Study Type: interventional
• Target: 955
• Locations: 29 countries
• Sites: 177

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

Conditions

Relapsing Multiple Scelrosis

Keywords

Relapsing multiple sclerosis; Ofatumumab; adult; OMB157; multiple sclerosis; T1 lesions; T2 lesions; relapse; GD-enhancing MRI; McDonald criteria; RRMS; SPMS

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (29)

• 3-month Confirmed Disability Worsening (3mCDW) Based on EDSS - Pooled Data

  Baseline, every 3 months up to 2.5 years

• 3-month Confirmed Disability Worsening (3mCDW) Based on EDSS - Study COMB157G2302

  Baseline, every 3 months up to 2.5 years

• 6-month Confirmed Disability Worsening (6mCDW) Based on EDSS - Pooled Data

  Baseline, every 3 months up to 2.5 years

• 6-month Confirmed Disability Worsening (6mCDW) Based on EDSS - Study COMB157G2302

  Baseline, every 3 months up to 2.5 years

• 6-month Confirmed Disability Improvement (6mCDI ) Based on EDSS - Pooled Data

  Baseline, every 3 months up to 2.5 years

Study Arms (2)

OMG 20 mg

EXPERIMENTAL

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; Drug: Teriflunomide-matching placebo capsules

TER 14 mg

ACTIVE COMPARATOR

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; Drug: Matching placebo of ofatumumab subcutaneous injections

Interventions

Ofatumumab subcutaneous injection DRUG

Ofatumumab 20 mg prefilled syringes for subcutaneous injection on days 1, 7, 14, week 4 and every 4 weeks thereafter

OMG 20 mg

Teriflunomide-matching placebo capsules DRUG

Placebo capsule, matching in appearance to teriflunomide, taken orally once daily

OMG 20 mg

Teriflunomide capsule DRUG

Teriflunomide 14 mg oral capsule taken once daily

TER 14 mg

Matching placebo of ofatumumab subcutaneous injections DRUG

Matching placebo of ofatumumab subcutaneous injections on days 1, 7, 14, week 4 and every 4 weeks thereafter

TER 14 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (178)

Novartis Investigative Site

Birmingham, Alabama, 35233-0271, United States

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Novartis Investigative Site

Cullman, Alabama, 35058, United States

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Novartis Investigative Site

Tucson, Arizona, 85704, United States

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Aurora, Colorado, 80045, United States

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Novartis Investigative Site

Basalt, Colorado, 81621, United States

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Boulder, Colorado, 80301, United States

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Novartis Investigative Site

Centennial, Colorado, 80112, United States

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Novartis Investigative Site

Colorado Springs, Colorado, 80907, United States

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Novartis Investigative Site

Denver, Colorado, 80210, United States

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Novartis Investigative Site

Fort Collins, Colorado, 80528, United States

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Novartis Investigative Site

Fort Collins, Colorado, 907-280528, United States

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Fairfield, Connecticut, 06824, United States

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Newark, Delaware, 19713, United States

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Bradenton, Florida, 34205, United States

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Gainesville, Florida, 32611, United States

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Maitland, Florida, 32751, United States

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Ocala, Florida, 34471, United States

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Oldsmar, Florida, 34677, United States

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Ormond Beach, Florida, 32174, United States

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Palm Coast, Florida, 32164, United States

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Sarasota, Florida, 34243, United States

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St. Petersburg, Florida, 33713, United States

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Tallahassee, Florida, 32312, United States

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Novartis Investigative Site

Tampa, Florida, 33603, United States

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Novartis Investigative Site

Tampa, Florida, 33609, United States

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Novartis Investigative Site

Tampa, Florida, 33612, United States

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Suwanee, Georgia, 30024, United States

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Anderson, Indiana, 46011, United States

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Indianapolis, Indiana, 46256, United States

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Wellesley, Massachusetts, 02481, United States

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Detroit, Michigan, 48202, United States

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Golden Valley, Minnesota, 55422, United States

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Billings, Montana, 59101, United States

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Great Falls, Montana, 59405, United States

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Albuquerque, New Mexico, 87131-0001, United States

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Asheville, North Carolina, 28806, United States

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Charlotte, North Carolina, 28202, United States

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Greensboro, North Carolina, 27405, United States

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Akron, Ohio, 44320, United States

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Columbus, Ohio, 43214, United States

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Columbus, Ohio, 43221, United States

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Westerville, Ohio, 43081, United States

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Portland, Oregon, 97225, United States

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Pittsburgh, Pennsylvania, 15212, United States

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Willow Grove, Pennsylvania, 19090, United States

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Greer, South Carolina, 29650, United States

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Cordova, Tennessee, 38018, United States

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Knoxville, Tennessee, 37922, United States

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Nashville, Tennessee, 37205, United States

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Greenville, Texas, 75401, United States

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Lubbock, Texas, 79410, United States

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Sherman, Texas, 75092, United States

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Orem, Utah, 84058, United States

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Salt Lake City, Utah, 84103, United States

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Salt Lake City, Utah, 84132, United States

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Kirkland, Washington, 98034, United States

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Seattle, Washington, 98122, United States

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Tacoma, Washington, 98405, United States

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Waukesha, Wisconsin, 53188, United States

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CABA, Buenos Aires, C1428AQK, Argentina

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Rosario, Santa Fe Province, S2000DSW, Argentina

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San Miguel de Tucumán, 4000, Argentina

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Liverpool, New South Wales, 2170, Australia

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Vienna, 1010, Austria

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Vienna, 1090, Austria

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Edegem, Antwerpen, 2650, Belgium

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Aalst, 9300, Belgium

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Brussels, 1200, Belgium

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Ghent, 9000, Belgium

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Sofia, 1113, Bulgaria

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Sofia, 1413, Bulgaria

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London, Ontario, N6A 5A5, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Greenfield Park, Quebec, J4V 2J2, Canada

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Osijek, 31000, Croatia

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Zagreb, 10000, Croatia

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Brno, Czech Republic, 656 91, Czechia

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Havířov, Czech Republic, 736 01, Czechia

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Teplice, Czech Republic, 415 01, Czechia

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Ostrava-Poruba, 708 52, Czechia

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Prague, 100 34, Czechia

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Tampere, 33100, Finland

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Turku, 20520, Finland

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Nice, Cedex1, 06001, France

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Bordeaux, 33076, France

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Clermont-Ferrand, 63000, France

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Montpellier, 34295, France

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Paris, 75651, France

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Rennes, 35033, France

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Strasbourg, 67098, France

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Bochum, 44791, Germany

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Cologne, 50935, Germany

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Dresden, 01307, Germany

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Essen, 45147, Germany

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Hamburg, 22179, Germany

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Hanover, 30625, Germany

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Heidelberg, 69120, Germany

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Homburg, 66421, Germany

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Leipzig, 04103, Germany

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Leipzig, 04107, Germany

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Minden, 32429, Germany

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Siegen, 57076, Germany

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Ulm, 89081, Germany

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Unterhaching, 82008, Germany

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Budapest, HUN, 1204, Hungary

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Esztergom, HUN, 2500, Hungary

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Hyderabad, Andhra Pradesh, 500018, India

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Mumbai, Maharashtra, 400008, India

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Mumbai, Maharashtra, 400012, India

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Pune, Maharashtra, 411004, India

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New Delhi, National Capital Territory of Delhi, 110 060, India

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Ludhiana, Punjab, 141008, India

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Mumbai, 400016, India

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Padua, PD, 35128, Italy

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Roma, RM, 00133, Italy

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Genova, 16132, Italy

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Milan, 20133, Italy

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Napoli, 80138, Italy

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Rome, 00178, Italy

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Riga, LV, LV-1005, Latvia

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Riga, LV 1002, Latvia

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Riga, LV-1038, Latvia

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Kaunas, LTU, LT 50161, Lithuania

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Vilnius, LT-08661, Lithuania

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Chihuahua City, 31238, Mexico

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Drammen, 1086, Norway

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Lima Cercado, Lima region, 01, Peru

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San Isidro, Lima region, 27, Peru

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Lima, LIMA 13, Peru

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Głogów, 36-060, Poland

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Rzeszów, 35 055, Poland

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Warsaw, 02 957, Poland

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Wroclaw, 51-685, Poland

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Zabrze, 41-800, Poland

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Matosinhos Municipality, Porto District, 4454509, Portugal

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Amadora, 2720-276, Portugal

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Braga, 4710243, Portugal

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Coimbra, 3000-075, Portugal

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Lisbon, 1169-050, Portugal

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Lisbon, 1500 650, Portugal

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Lisbon, 1600190, Portugal

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Loures, 2674514, Portugal

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Porto, 4000001, Portugal

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Santa Maria da Feira, 4520 211, Portugal

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Kazan', 420021, Russia

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Krasnoyarsk, 660049, Russia

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Moscow, 127015, Russia

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Nizhny Novgorod, 603137, Russia

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Novosibirsk, 630087, Russia

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Saint Petersburg, 197022, Russia

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Saint Petersburg, 197110, Russia

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Saint Petersburg, 197376, Russia

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Yekaterinburg, 620109, Russia

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Bratislava, 813 69, Slovakia

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Martin, 036 59, Slovakia

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Ružomberok, 03426, Slovakia

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Pretoria, 0041, South Africa

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Rosebank, 2196, South Africa

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Málaga, Andalusia, 29010, Spain

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Seville, Andalusia, 41017, Spain

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Pozuelo de Alarcón, Madrid, 28223, Spain

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Barakaldo, Vizcaya, 48903, Spain

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Donostia / San Sebastian, 20014, Spain

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Madrid, 28006, Spain

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Madrid, 28034, Spain

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Madrid, 28040, Spain

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Madrid, 28222, Spain

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Lugano, 6900, Switzerland

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Tainan, 70403, Taiwan

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Haseki / Istanbul, 34096, Turkey (Türkiye)

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Izmir, 35340, Turkey (Türkiye)

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Mersin, 33079, Turkey (Türkiye)

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Trabzon, 61080, Turkey (Türkiye)

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Luton, Beds, LU4 0DZ, United Kingdom

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Sheffield, South Yorkshire, S10 2JF, United Kingdom

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London, SE5 9RS, United Kingdom

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London, SW17 0QT, United Kingdom

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Related Publications (4)

• Williams MJ, Amezcua L, Cohan SL, Cohen JA, Delgado SR, Hua LH, Lucassen EB, Piccolo RS, Koulouris CR, Stankiewicz J. Efficacy of Ofatumumab and Teriflunomide in Patients With Relapsing MS From Racial/Ethnic Minority Groups: ASCLEPIOS I/II Subgroup Analyses. Neurology. 2024 Aug 13;103(3):e209610. doi: 10.1212/WNL.0000000000209610. Epub 2024 Jul 17.

  PMID: 39018512 DERIVED

• Bhan V, Clift F, Baharnoori M, Thomas K, Patel BP, Blanchette F, Adlard N, Vudumula U, Gudala K, Dutta N, Grima D, Mouallif S, Farhane F. Cost-consequence analysis of ofatumumab for the treatment of relapsing-remitting multiple sclerosis in Canada. J Comp Eff Res. 2023 Sep;12(9):e220175. doi: 10.57264/cer-2022-0175. Epub 2023 Aug 22.

  PMID: 37606897 DERIVED

• 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.

  PMID: 35266417 DERIVED

• 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.

  PMID: 32757523 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis; Recurrence

Interventions

teriflunomide

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

This study was not powered for the analysis of some secondary endpoints as a stand-alone study. It was pre-specified in the study protocol to combine the data with study COMB157G2301 to address these endpoints.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2016
• First Posted: June 7, 2016
• Study Start: August 26, 2016
• Primary Completion: July 10, 2019
• Study Completion: October 22, 2020
• Last Updated: November 22, 2021
• Results First Posted: October 19, 2020

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share

Locations

ES (9); CH (1); RU (9); NO (1); IT (6); GB (4); LA (3); US (59); CA (4); LI (2); SL (3); IN (7); TU (4); HU (2); FR (7); DE (14); ZA (2); CZ (5); AR (3); FI (2); BU (2); BE (4); PL (5); CR (2); TW (1); ME (1); PT (10); PE (3); AU (2)