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

NCT02792218 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: COMB157G23012015-005418-31
• Study Type: interventional
• Target: 930
• Locations: 28 countries
• Sites: 157

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 Sclerosis

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 COMB157G2301

  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 COMB157G2301

  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)

OMB 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 pre-filled syringes for subcutaneous injection on days 1, 7, 14, week 4 and every 4 weeks thereafter

OMB 20 mg

Teriflunomide-matching placebo capsules DRUG

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

OMB 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:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (166)

Novartis Investigative Site

Phoenix, Arizona, 85013, United States

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Berkeley, California, 94705, United States

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Fullerton, California, 92835, United States

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Sacramento, California, 95817, United States

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Washington D.C., District of Columbia, 20007, United States

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Atlantis, Florida, 33462-6608, United States

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Delray Beach, Florida, 33445, United States

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Hollywood, Florida, 33021, United States

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Loxahatchee Groves, Florida, 33470, United States

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Miami, Florida, 33032, United States

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Miami, Florida, 33136, United States

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Naples, Florida, 34102, United States

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North Palm Beach, Florida, 33408, United States

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Pensacola, Florida, 32514, United States

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Port Charlotte, Florida, 33952, United States

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Sunrise, Florida, 33351, United States

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Vero Beach, Florida, 32960, United States

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West Palm Beach, Florida, 33407, United States

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Savannah, Georgia, 31406, United States

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Honolulu, Hawaii, 96817, United States

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Chicago, Illinois, 60612, United States

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Northbrook, Illinois, 60062, United States

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Indianapolis, Indiana, 46202, United States

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Des Moines, Iowa, 50314-2611, United States

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Kansas City, Kansas, 66160, United States

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Overland Park, Kansas, 66210, United States

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Alexandria, Louisiana, 71301, United States

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Baton Rouge, Louisiana, 70810, United States

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Clinton Township, Michigan, 48035, United States

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Detroit, Michigan, 48201, United States

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Golden Valley, Minnesota, 55422, United States

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Chesterfield, Missouri, 63017, United States

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Ozark, Missouri, 65721, United States

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St Louis, Missouri, 63110, United States

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Las Vegas, Nevada, 89106, United States

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Latham, New York, 12110, United States

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Charlotte, North Carolina, 28204, United States

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Raleigh, North Carolina, 27607, United States

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Winston-Salem, North Carolina, 27103, United States

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Winston-Salem, North Carolina, 27157, United States

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Cleveland, Ohio, 44195, United States

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Oklahoma City, Oklahoma, 73104, United States

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Spartanburg, South Carolina, 29303, United States

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Johnson City, Tennessee, 37604, United States

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Knoxville, Tennessee, 37920, United States

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Dallas, Texas, 75246, United States

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El Paso, Texas, 79935, United States

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Houston, Texas, 77074, United States

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Round Rock, Texas, 78681, United States

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San Antonio, Texas, 78229, United States

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San Antonio, Texas, 78258, United States

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Virginia Beach, Virginia, 23456, United States

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Green Bay, Wisconsin, 54311, United States

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Madison, Wisconsin, 53792, United States

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Milwaukee, Wisconsin, 53215, United States

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Neenah, Wisconsin, 54956, United States

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Rosario, Santa Fe Province, S2000BZL, Argentina

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Buenos Aires, 1061, Argentina

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Córdoba, X5004CDT, Argentina

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New Lambton Heights, New South Wales, 2305, Australia

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St Leonards, New South Wales, 2065, Australia

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Brasschaat, 2930, Belgium

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Bruges, 8000, Belgium

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Liège, 4000, Belgium

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Overpelt, 3900, Belgium

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Plovdiv, 4002, Bulgaria

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Sofia, 1309, Bulgaria

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Sofia, 1431, Bulgaria

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Vancouver, British Columbia, V6T 1Z3, Canada

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Gatineau, Quebec, J9J 0A5, Canada

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Montreal, Quebec, H3A 2B4, Canada

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Québec, Quebec, G1J 1Z4, Canada

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Rijeka, HRV, 51000, Croatia

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Zagreb, 10000, Croatia

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Praha 4 Krc, Czech Republic, 140 59, Czechia

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Hradec Králové, CZE, 500 05, Czechia

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Olomouc, CZE, 775 20, Czechia

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Jihlava, 586 01, Czechia

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Pardubice, 532 03, Czechia

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Prague, 150 06, Czechia

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Aarhus, 8000, Denmark

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Copenhagen, DK-2100, Denmark

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Odense C, 5000, Denmark

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Tallinn, 10617, Estonia

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Tartu, 51014, Estonia

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Nancy, Cedex, 54035, France

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Lille, 59037, France

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Nantes, 44093, France

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Nîmes, 30029, France

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Barsinghausen, 30890, Germany

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Bayreuth, 95445, Germany

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Bielefeld, D 33647, Germany

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Hamburg, 20249, Germany

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Marburg, 35043, Germany

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München, 80377, Germany

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München, 81377, Germany

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Neuburg an der Donau, 86633, Germany

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Potsdam, 14471, Germany

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Ulm, 89073, Germany

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Wiesbaden, 65191, Germany

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Athens, GR, 115 25, Greece

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Athens, 115 28, Greece

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Thessaloniki, GR 54636, Greece

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Budapest, HUN, 1135, Hungary

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Budapest, 1106, Hungary

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Kistarcsa, 2143, Hungary

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Szeged, 6725, Hungary

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Bangalore, Karnataka, 560054, India

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Kochi, Kerala, 682 026, India

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New Delhi, National Capital Territory of Delhi, 110017, India

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Chandigarh, Punjab, 160012, India

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Kolkata, West Bengal, 700068, India

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Mangalore, 575018, India

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Ashkelon, 78278, Israel

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Haifa, 310 9601, Israel

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Sefad, 13100, Israel

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Tel Aviv, 6423906, Israel

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Milan, MI, 20132, Italy

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Roma, RM, 00189, Italy

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Gallarate, VA, 21013, Italy

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Napoli, 80131, Italy

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Mexico City, Mexico City, 03100, Mexico

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Sittard-Geleen, BG, 6162 BG, Netherlands

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Amsterdam, 1081 HV, Netherlands

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Rotterdam, 3015 CE, Netherlands

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Bydgoszcz, 85-796, Poland

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Gdansk, 80 952, Poland

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Gdansk, 80-462, Poland

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Gdansk, 80-803, Poland

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Katowice, 40 571, Poland

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Kielce, 25 726, Poland

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Lodz, 90 324, Poland

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Guaynabo, 00968, Puerto Rico

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Kemerovo, 650066, Russia

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Moscow, 125367, Russia

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Nizhny Novgorod, 603155, Russia

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Novosibirsk, 630007, Russia

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Saint Petersburg, 194044, Russia

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Saransk, 430032, Russia

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Sestroretsk, 197706, Russia

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Tyumen, 625000, Russia

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Banská Bystrica, 97517, Slovakia

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Bratislava, 82606, Slovakia

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Bratislava, 83305, Slovakia

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Nitra, 94901, Slovakia

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Trnava, 917 75, Slovakia

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Cadiz, Andalusia, 11009, Spain

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Barcelona, Catalonia, 08026, Spain

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Barcelona, Catalonia, 08035, Spain

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Barcelona, Catalonia, 08036, Spain

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L'Hospitalet de Llobregat, Catalonia, 08907, Spain

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Salt, Catalonia, 17190, Spain

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El Palmar, Murcia, 30120, Spain

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Barcelona, 08003, Spain

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Valencia, 46026, Spain

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Gothenburg, 413 45, Sweden

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Stockholm, 102 35, Sweden

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Basel, 4031, Switzerland

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Khon Kaen, THA, 40002, Thailand

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Istanbul, 34147, Turkey (Türkiye)

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Izmir, 35040, Turkey (Türkiye)

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Kocaeli, 41380, Turkey (Türkiye)

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Samsun, 55139, Turkey (Türkiye)

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Headington, Oxfordshire, OX3 9DU, United Kingdom

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Glasgow, G51 4TF, United Kingdom

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London, E1 1BB, 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 COMB157G2302 to address these endpoints.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

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: September 20, 2016
• Primary Completion: July 5, 2019
• Study Completion: July 20, 2020
• Last Updated: October 1, 2021
• Results First Posted: October 19, 2020

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will share

Locations

IL (4); NL (3); ES (2); AR (3); SE (2); FR (4); US (56); BE (4); DK (3); PL (7); DE (11); CH (1); GR (3); HU (4); BU (3); ME (1); SL (5); CZ (6); TH (1); CR (2); IT (4); RU (8); CA (4); PR (1); TU (4); GB (3); AU (2); IN (6)