Clinical trial NCT01061736: Evaluation of Sarilumab (SAR153191/REGN88) on Top of Methotrexate in Rheumatoid Arthritis Patients
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter, Two-part, Dose Ranging and Confirmatory Study With an Operationally Seamless Design, Evaluating Efficacy and Safety of SAR153191 on Top of Methotrexate (MTX) in Patients With Active Rheumatoid Arthritis Who Are Inadequate Responders to MTX Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Rheumatoid Arthritis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2010-02-03
Enrollment: 1675
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objectives:

Part A (dose ranging study):

To demonstrate that sarilumab (SAR153191/REGN88) on top of MTX was effective on reduction of signs and symptoms of rheumatoid arthritis at 12 weeks.

Part B (pivotal study):

To demonstrate that sarilumab added to MTX was effective in:

* reduction of signs and symptoms of rheumatoid arthritis at 24 weeks
* inhibition of progression of structural damage at 52 weeks
* improvement in physical function at 16 weeks

Secondary Objectives:

Part B:

To demonstrate that sarilumab added to MTX was effective in induction of a major clinical response at 52 weeks

To assess the safety of sarilumab added to MTX

To document the pharmacokinetic profile of sarilumab added to MTX in participants with active rheumatoid arthritis who were inadequate responders to MTX therapy.

Detailed description: The total study duration for a participant was 16-22 weeks (Part A) and 56-62 weeks (Part B) broken down as follows:

* Screening: Up to 4 weeks
* Treatment: 12 weeks (Part A) and 52 weeks (Part B)\*
* Follow-up: 6 weeks (for participants who would not continue in the long-term extension study).

'\*' Participants successfully completing their treatment period would be offered the opportunity to enter the long term extension study LTS11210 (SARIL-RA-EXTEND) (NCT01146652).

Eligibility criteria: Inclusion criteria :

* Diagnosis of rheumatoid arthritis ≥3 months duration
* Active disease defined as:

  * at least 8/68 tender joints and 6/66 swollen joints,
  * high sensitivity C-reactive protein (hs-CRP) \>6 mg/l,
  * continuous treatment with MTX for at least 12 weeks prior to baseline visit and on stable dose for at least 6 weeks prior to screening visit.

Part B only:

* Bone erosion based on documented X-ray prior to first study drug intake, or
* Cyclic Citrullinated Peptide (CCP) positive, or
* Rheumatoid Factor (RF) positive.

Exclusion criteria:

* Age \<18 years or \>75 years.
* Treatment with disease-modifying antirheumatic drugs (DMARDs) other than MTX within 4 weeks or 12 weeks prior to screening (depending on DMARDs).
* Past history of non-response to prior Tumor Necrosis Factor (TNF) or biologic treatment.
* Any past or current biologic agents for the treatment of rheumatoid arthritis within 3 months.
* Use of parenteral glucocorticoids or intraarticular glucocorticoids within 4 weeks prior to screening visit.
* Use of oral glucocorticoid greater than 10mg/day or equivalent/day, or a change in dosage within 4 weeks prior to baseline visit.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Primary outcomes:
measure: Part A: Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12
timeFrame: Baseline to Week 12
measure: Part B: Percentage of Participants Achieving ACR20 Response at Week 24
timeFrame: Baseline to Week 24
measure: Part B: Change From Baseline in Health Assessment Question Disability Index (HAQ-DI) at Week 16
timeFrame: Baseline, Week 16
measure: Part B: Change From Baseline in Van Der Heijde Modified Total Sharp Score (mTSS) at Week 52
timeFrame: Baseline, Week 52
Secondary outcomes:
measure: Part B: Percentage of Participants Achieving a Major Clinical Response at Week 52
timeFrame: Baseline up to Week 52
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Investigational Site Number 840070
state: Alabama
city: Birmingham
country: United States
facility: Investigational Site Number 840004
state: Alabama
city: Gilbert
country: United States
facility: Investigational Site Number 840072
state: Arizona
city: Beverly Hills
country: United States
facility: Investigational Site Number 840029
state: California
city: Palm Desert
country: United States
facility: Investigational Site Number 840007
state: California
city: San Francisco
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state: California
city: Santa Maria
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city: Upland
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city: Miami
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city: Orlando
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city: Palm Harbor
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city: Sarasota
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state: Florida
city: Atlanta
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city: Decatur
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city: Marietta
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city: Idaho Falls
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state: Idaho
city: Chicago
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state: Illinois
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state: Kentucky
city: Cumberland
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state: Maryland
city: Frederick
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city: Wheaton
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state: Maryland
city: Saint Louis
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state: Missouri
city: Omaha
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state: Nebraska
city: New York
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state: New York
city: Hickory
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state: North Carolina
city: Toledo
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state: Ohio
city: Oklahoma City
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state: Oklahoma
city: Tulsa
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state: Oklahoma
city: Tulsa
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state: Oklahoma
city: Bethlehem
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state: Pennsylvania
city: Duncansville
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state: Pennsylvania
city: Reading
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state: Pennsylvania
city: Columbia
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state: South Carolina
city: North Charleston
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state: South Carolina
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state: Tennessee
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city: Dallas
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state: Texas
city: Mesquite
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state: Texas
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state: Washington
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city: Heidelberg West
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city: St Leonards
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city: Victoria Park
country: Australia
facility: Investigational Site Number 036014
city: Woodville
country: Australia
facility: Investigational Site Number 036007
city: Graz
country: Austria
facility: Investigational Site Number 040001
city: Wien
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city: Genk
country: Belgium
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country: Belgium
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city: Campinas
country: Brazil
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country: Brazil
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country: Brazil
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country: Brazil
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city: Burlington
country: Canada
facility: Investigational Site Number 124004
city: Mississauga
country: Canada
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city: Newmarket
country: Canada
facility: Investigational Site Number 124008
city: St. Catharines
country: Canada
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country: Canada
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city: Winnipeg
country: Canada
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city: Osorno
country: Chile
facility: Investigational Site Number 152005
city: Puerto Montt
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country: Chile
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country: Colombia
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country: Colombia
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country: Colombia
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city: Medellin
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country: Czechia
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city: Praha 2
country: Czechia
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city: Uherske Hradiste
country: Czechia
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city: Cairo
country: Egypt
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country: Egypt
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city: Tallinn
country: Estonia
facility: Investigational Site Number 233001
city: Tallinn
country: Estonia
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city: Helsinki
country: Finland
facility: Investigational Site Number 246001
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country: Finland
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city: Pori
country: Finland
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city: Berlin
country: Germany
facility: Investigational Site Number 276007
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country: Germany
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city: Erlangen
country: Germany
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country: Germany
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country: Germany
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country: Germany
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country: Greece
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country: Hungary
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country: India
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city: New Delhi
country: India
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city: Anyang
country: Korea, Republic of
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country: Korea, Republic of
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country: Korea, Republic of
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city: Daegu
country: Korea, Republic of
facility: Investigational Site Number 410013
city: Daejeon
country: Korea, Republic of
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city: Gwangju
country: Korea, Republic of
facility: Investigational Site Number 410010
city: Incheon
country: Korea, Republic of
facility: Investigational Site Number 410009
city: Incheon
country: Korea, Republic of
facility: Investigational Site Number 410001
city: Jeonju
country: Korea, Republic of
facility: Investigational Site Number 410011
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410007
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410012
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410003
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410002
city: Suwon
country: Korea, Republic of
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country: Lithuania
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country: Malaysia
facility: Investigational Site Number 458001
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country: Mexico
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country: New Zealand
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country: Norway
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city: Aveiro
country: Portugal
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city: Lisboa
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city: Lisboa
country: Portugal
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city: Braila
country: Romania
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country: Romania
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city: Galati
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city: Kemerovo
country: Russian Federation
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city: Kemerovo
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city: Moscow
country: Russian Federation
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country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Moscow
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city: Moscow
country: Russian Federation
facility: Investigational Site Number 643012
city: Novosibirsk
country: Russian Federation
facility: Investigational Site Number 643009
city: Ryazan
country: Russian Federation
facility: Investigational Site Number 643016
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 643014
city: Samara
country: Russian Federation
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city: Saratov
country: Russian Federation
facility: Investigational Site Number 643011
city: St-Petersburg
country: Russian Federation
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city: St-Petersburg
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city: Ufa
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city: Cape Town
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country: South Africa
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country: South Africa
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country: South Africa
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city: Durban
country: South Africa
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city: Johannesburg
country: South Africa
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city: Kempton Park
country: South Africa
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city: Pretoria
country: South Africa
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city: Pretoria
country: South Africa
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city: Pretoria
country: South Africa
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city: Stellenbosch
country: South Africa
facility: Investigational Site Number 710010
city: Barcelona
country: Spain
facility: Investigational Site Number 724010
city: La Coruña
country: Spain
facility: Investigational Site Number 724009
city: Sabadell
country: Spain
facility: Investigational Site Number 724011
city: Santiago De Compostela
country: Spain
facility: Investigational Site Number 724012
city: Sevilla
country: Spain
facility: Investigational Site Number 724007
city: Linkou
country: Taiwan
facility: Investigational Site Number 158002
city: Taipei
country: Taiwan
facility: Investigational Site Number 158001
city: Bangkok
country: Thailand
facility: Investigational Site Number 764001
city: Bangkok
country: Thailand
facility: Investigational Site Number 764003
city: Adana
country: Turkey
facility: Investigational Site Number 792003
city: Ankara
country: Turkey
facility: Investigational Site Number 792002
city: Ankara
country: Turkey
facility: Investigational Site Number 792005
city: Antalya
country: Turkey
facility: Investigational Site Number 792004
city: Izmir
country: Turkey
facility: Investigational Site Number 792001
city: Dnipropetrovsk
country: Ukraine
facility: Investigational Site Number 804003
city: Donetsk
country: Ukraine
facility: Investigational Site Number 804002
city: Kharkov
country: Ukraine
facility: Investigational Site Number 804010
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804008
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804004
city: Lviv
country: Ukraine
facility: Investigational Site Number 804005
city: Simferopol
country: Ukraine
facility: Investigational Site Number 804006
city: Zaporizhzhia
country: Ukraine
facility: Investigational Site Number 804009
Study officials:
affiliation: Division of Immunology and Rheumatology - Stanford University - USA
name: Mark C Genovese, MD, Professor of Medicine
role: PRINCIPAL_INVESTIGATOR
affiliation: Dpt of Rheumatology - Leiden University Medical Center - The Netherlands
name: TWJ Huizinga, Prof Dr
role: STUDY_CHAIR
References:
citation: Strand V, Kosinski M, Chen CI, Joseph G, Rendas-Baum R, Graham NM, van Hoogstraten H, Bayliss M, Fan C, Huizinga T, Genovese MC. Sarilumab plus methotrexate improves patient-reported outcomes in patients with active rheumatoid arthritis and inadequate responses to methotrexate: results of a phase III trial. Arthritis Res Ther. 2016 Sep 6;18(1):198. doi: 10.1186/s13075-016-1096-9.
citation: Huizinga TW, Fleischmann RM, Jasson M, Radin AR, van Adelsberg J, Fiore S, Huang X, Yancopoulos GD, Stahl N, Genovese MC. Sarilumab, a fully human monoclonal antibody against IL-6Ralpha in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial. Ann Rheum Dis. 2014 Sep;73(9):1626-34. doi: 10.1136/annrheumdis-2013-204405. Epub 2013 Dec 2.
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