Clinical trial NCT02792218: 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 Sclerosis
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: 930
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 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).

Eligibility 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

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 COMB157G2301
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 COMB157G2301
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 COMB157G2301
timeFrame: Baseline, every 3 months up to 2.5 years
measure: Number of Gd-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: Percentage of 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: Annual Rate of Percent Change in 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:
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state: Texas
city: San Antonio
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state: Texas
city: San Antonio
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state: Texas
city: Virginia Beach
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state: Virginia
city: Green Bay
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state: Wisconsin
city: Madison
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city: Milwaukee
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state: Wisconsin
city: Neenah
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state: Wisconsin
city: Rosario
country: Argentina
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state: Santa Fe
city: Buenos Aires
country: Argentina
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city: Cordoba
country: Argentina
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city: New Lambton Heights
country: Australia
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state: New South Wales
city: St Leonards
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state: New South Wales
city: Brasschaat
country: Belgium
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city: Brugge
country: Belgium
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city: Liege
country: Belgium
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city: Pelt
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city: Plovdiv
country: Bulgaria
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city: Sofia
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city: Sofia
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city: Vancouver
country: Canada
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state: British Columbia
city: Gatineau
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state: Quebec
city: Montreal
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state: Quebec
city: Quebec
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city: Rijeka
country: Croatia
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state: HRV
city: Zagreb
country: Croatia
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city: Praha 4 Krc
country: Czechia
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state: Czech Republic
city: Hradec Kralove
country: Czechia
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state: CZE
city: Olomouc
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state: CZE
city: JIhlava
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city: Pardubice
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city: Copenhagen
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country: France
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country: Greece
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country: Hungary
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city: Tel Aviv
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country: Italy
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city: Gallarate
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city: Napoli
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country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Sittard-Geleen
country: Netherlands
facility: Novartis Investigative Site
state: BG
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Bydgoszcz
country: Poland
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Gdansk
country: Poland
facility: Novartis Investigative Site
city: Katowice
country: Poland
facility: Novartis Investigative Site
city: Kielce
country: Poland
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city: Lodz
country: Poland
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city: Guaynabo
country: Puerto Rico
facility: Novartis Investigative Site
city: Kemerovo
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: Saransk
country: Russian Federation
facility: Novartis Investigative Site
city: Sestroretsk
country: Russian Federation
facility: Novartis Investigative Site
city: Tyumen
country: Russian Federation
facility: Novartis Investigative Site
city: Banska Bystrica
country: Slovakia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Nitra
country: Slovakia
facility: Novartis Investigative Site
city: Trnava
country: Slovakia
facility: Novartis Investigative Site
city: Cadiz
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluna
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Cataluna
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: L Hospitalet De Llobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Salt
country: Spain
facility: Novartis Investigative Site
state: Cataluña
city: El Palmar
country: Spain
facility: Novartis Investigative Site
state: Murcia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Goeteborg
country: Sweden
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Basel
country: Switzerland
facility: Novartis Investigative Site
city: Khon Kaen
country: Thailand
facility: Novartis Investigative Site
state: THA
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
city: Samsun
country: Turkey
facility: Novartis Investigative Site
city: Headington
country: United Kingdom
facility: Novartis Investigative Site
state: Oxfordshire
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
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.