Clinical trial NCT02792231: Efficacy and Safety of Ofatumumab Compared to Teriflunomide in Patients With Relapsing Multiple Sclerosis.
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2016-06-07
Enrollment: 955
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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).

Eligibility criteria: Inclusion Criteria:

* Male or female patients aged 18 to 55 years at Screening
* Diagnosis of multiple sclerosis (MS)
* Relapsing MS: relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) with disease activity
* Documentation of at least: 1 relapse during the previous 1 year OR 2 relapses during the previous 2 years OR a positive gadolinium-enhancing MRI scan during the year prior to randomization
* Disability status at Screening with an Expanded Disability Status Scale (EDSS) score of 0 to 5.5
* Neurologically stable within 1 month prior to randomization

Exclusion Criteria:

* Patients with primary progressive MS or SPMS without disease activity
* Disease duration of more than 10 years in patients with an EDSS score of 2 or less
* Patients with an active chronic disease of the immune system other than MS
* Patients at risk of developing or having reactivation of hepatitis
* Patients with active systemic infections or with neurological findings consistent with PML

Primary outcomes:
measure: Annualized Relapse Rate (ARR)
timeFrame: Baseline up to 2.5 years
Secondary outcomes:
measure: 3-month Confirmed Disability Worsening (3mCDW) Based on EDSS - Pooled Data
timeFrame: Baseline, every 3 months up to 2.5 years
measure: 3-month Confirmed Disability Worsening (3mCDW) Based on EDSS - Study COMB157G2302
timeFrame: Baseline, every 3 months up to 2.5 years
measure: 6-month Confirmed Disability Worsening (6mCDW) Based on EDSS - Pooled Data
timeFrame: Baseline, every 3 months up to 2.5 years
measure: 6-month Confirmed Disability Worsening (6mCDW) Based on EDSS - Study COMB157G2302
timeFrame: Baseline, every 3 months up to 2.5 years
measure: 6-month Confirmed Disability Improvement (6mCDI ) Based on EDSS - Pooled Data
timeFrame: Baseline, every 3 months up to 2.5 years
measure: 6-month Confirmed Disability Improvement (6mCDI ) Based on EDSS - Study COMB157G2302
timeFrame: Baseline, every 3 months up to 2.5 years
measure: Number of Gadolinium-enhancing T1 Lesions Per MRI Scan
timeFrame: Baseline, yearly up to 2.5 years
measure: Number of New or Enlarging T2 Lesions on MRI Per Year (Annualized Lesion Rate)
timeFrame: Baseline, yearly up to 2.5 years
measure: Neurofilament Light Chain (NfL) Concentration in Serum
timeFrame: Month 3, 12 and 24
measure: Annualized Rate of Brain Volume Loss Based on Assessments of Percent Brain Volume Change From Baseline
timeFrame: Baseline, Months 12 and 24
measure: Participants With Confirmed Relapse
timeFrame: Baseline up to 2.5 years
measure: Annualized Relapse Rate (ARR) >8 Weeks After Onset of Treatment
timeFrame: Baseline up to 2.5 years
measure: 3-month Confirmed Disability Worsening (3mCDW) Based on EDSS > 8 Weeks After Onset of Treatment - Pooled Data
timeFrame: Baseline up to 2.5 years
measure: 6-month Confirmed Disability Worsening (6mCDW) Based on EDSS > 8 Weeks After Onset of Treatment - Pooled Data
timeFrame: Baseline up to 2.5 years
measure: 6-month Confirmed Cognitive Decline on Symbol Digit Modalities Test (SDMT) - Pooled Data
timeFrame: Baseline, every 6 months up to 2.5 years
measure: 6-month Confirmed Disability Worsening (6mCDW) or 6-month Confirmed Cognitive Decline (6mCCD) - Pooled Data
timeFrame: Baseline up to 2.5 years
measure: Change in Cognitive Performance Measured by the Symbol Digit Modalities Test (SDMT) - Pooled Data
timeFrame: Baseline up to 2.5 years
measure: 6-month Confirmed Worsening of at Least 20% in the Timed 25-Foot Walk (T25FW) - Pooled Data
timeFrame: Baseline, every 3 months up to 2.5 years
measure: 6-month Confirmed Worsening of at Least 20% in the 9-Hole Peg Test (9HPT) - Pooled Data
timeFrame: Baseline, every 6 months up to 2.5 years
measure: 6-month Confirmed Disability Improvement (6mCDI) Sustained Until End of Study (EOS) as Measured by EDSS - Pooled Data
timeFrame: Baseline, every 3 months up to 2.5 years
measure: Number of New or Enlarging T2 Lesions on MRI Per Year From Month 12 Until End of Study (EOS)
timeFrame: Month 12 up to 2.5 years
measure: Percent Change in T2 Lesion Volume Relative to Baseline
timeFrame: Baseline, Month 12, Month 24
measure: No Evidence of Disease Activity (NEDA-4)
timeFrame: Baseline, Month 12, Month 24
measure: Multiple Sclerosis Impact Scale (MSIS-29) Physical Impact Score Change From Baseline
timeFrame: Baseline, every 6 months up to 2.5 years
measure: Multiple Sclerosis Impact Scale (MSIS-29) Psychological Impact Score Change From Baseline
timeFrame: Baseline, every 6 months up to 2.5 years
measure: Annualized Relapse Rates (ARR) by NfL High-low Subgroups - Pooled Data
timeFrame: Baseline up to 2.5 years
measure: Number of New or Enlarging T2 Lesions Per Year by NfL High-low Subgroups - Pooled Data
timeFrame: Baseline, yearly up to 2.5 years
measure: Brain Volume Loss by NfL High-low Subgroups - Pooled Data
timeFrame: Baseline, Months 12 and 24
measure: Pharmacokinetic (PK) Concentrations of Ofatumumab
timeFrame: Baseline, Weeks 4, 12, 24, 48, 96
Other outcomes:
Locations:
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country: United States
facility: Novartis Investigative Site
state: Alabama
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city: Tucson
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city: Oldsmar
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city: Ormond Beach
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city: Palm Coast
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city: Sarasota
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city: Tallahassee
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state: Florida
city: Tampa
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state: Florida
city: Tampa
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city: Tampa
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city: Knoxville
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state: Tennessee
city: Nashville
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state: Tennessee
city: Greenville
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state: Texas
city: Lubbock
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facility: Novartis Investigative Site
state: Texas
city: Sherman
country: United States
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state: Texas
city: Orem
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state: Utah
city: Salt Lake City
country: United States
facility: Novartis Investigative Site
state: Utah
city: Salt Lake City
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facility: Novartis Investigative Site
state: Utah
city: Kirkland
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state: Washington
city: Seattle
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state: Washington
city: Tacoma
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state: Washington
city: Waukesha
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state: Wisconsin
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Rosario
country: Argentina
facility: Novartis Investigative Site
state: Santa Fe
city: Tucuman
country: Argentina
facility: Novartis Investigative Site
city: Liverpool
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Wien
country: Austria
facility: Novartis Investigative Site
city: Edegem
country: Belgium
facility: Novartis Investigative Site
state: Antwerpen
city: Aalst
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
facility: Novartis Investigative Site
city: Sofia
country: Bulgaria
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city: London
country: Canada
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state: Ontario
city: Ottawa
country: Canada
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state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Greenfield Park
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Osijek
country: Croatia
facility: Novartis Investigative Site
city: Zagreb
country: Croatia
facility: Novartis Investigative Site
city: Brno
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Havirov
country: Czechia
facility: Novartis Investigative Site
state: Czech Republic
city: Teplice
country: Czechia
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state: Czech Republic
city: Ostrava-Poruba
country: Czechia
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country: Czechia
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country: Finland
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city: Turku
country: Finland
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city: Nice
country: France
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state: Cedex1
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Clermont-Ferrand
country: France
facility: Novartis Investigative Site
city: Montpellier
country: France
facility: Novartis Investigative Site
city: Paris Cedex 13
country: France
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city: Rennes Cedex
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
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city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
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city: Heidelberg
country: Germany
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city: Homburg
country: Germany
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city: Koln
country: Germany
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city: Leipzig
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city: Leipzig
country: Germany
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city: Unterhaching
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city: Budapest
country: Hungary
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state: HUN
city: Esztergom
country: Hungary
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state: Andhra Pradesh
city: New Delhi
country: India
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state: Delhi
city: Mumbai
country: India
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state: Maharashtra
city: Mumbai
country: India
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city: Pune
country: India
facility: Novartis Investigative Site
state: Maharashtra
city: Ludhiana
country: India
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state: Punjab
city: Mumbai
country: India
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city: Padova
country: Italy
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state: PD
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Genova
country: Italy
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Rome
country: Italy
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city: Riga
country: Latvia
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state: LV
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Riga
country: Latvia
facility: Novartis Investigative Site
city: Kaunas
country: Lithuania
facility: Novartis Investigative Site
state: LTU
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
city: Chihuahua
country: Mexico
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city: Drammen
country: Norway
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city: Cercado De Lima
country: Peru
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state: Lima
city: San Isidro
country: Peru
facility: Novartis Investigative Site
state: Lima
city: Lima
country: Peru
facility: Novartis Investigative Site
city: Glogow
country: Poland
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city: Rzeszow
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Zabrze
country: Poland
facility: Novartis Investigative Site
city: Matosinhos
country: Portugal
facility: Novartis Investigative Site
state: Porto
city: Amadora
country: Portugal
facility: Novartis Investigative Site
city: Braga
country: Portugal
facility: Novartis Investigative Site
city: Coimbra
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Loures
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Santa Maria da Feira
country: Portugal
facility: Novartis Investigative Site
city: Ekaterinburg
country: Russian Federation
facility: Novartis Investigative Site
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
city: Krasnoyarsk
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Nizhny Novgorod
country: Russian Federation
facility: Novartis Investigative Site
city: Novosibirsk
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St. Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Martin
country: Slovakia
facility: Novartis Investigative Site
city: Ruzomberok
country: Slovakia
facility: Novartis Investigative Site
city: Pretoria
country: South Africa
facility: Novartis Investigative Site
city: Rosebank
country: South Africa
facility: Novartis Investigative Site
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Pozuelo de Alarcon
country: Spain
facility: Novartis Investigative Site
state: Madrid
city: Baracaldo
country: Spain
facility: Novartis Investigative Site
state: Vizcaya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: San Sebastian
country: Spain
facility: Novartis Investigative Site
city: Lugano
country: Switzerland
facility: Novartis Investigative Site
city: Tainan
country: Taiwan
facility: Novartis Investigative Site
city: Haseki / Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Mersin
country: Turkey
facility: Novartis Investigative Site
city: Trabzon
country: Turkey
facility: Novartis Investigative Site
city: Luton
country: United Kingdom
facility: Novartis Investigative Site
state: Beds
city: Sheffield
country: United Kingdom
facility: Novartis Investigative Site
state: South Yorkshire
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.