Clinical trial NCT01061723: Dose Ranging Study to Evaluate the Efficacy and Safety of SAR153191 (REGN88) in Patients With Ankylosing Spondylitis
Official title: A Randomized Double Blind-placebo Controlled Dose Ranging Study to Evaluate the Efficacy and Safety of SAR153191 in Participants With Ankylosing Spondylitis (AS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ankylosing Spondylitis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2010-02-03
Enrollment: 301
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 objective:

- to evaluate the efficacy of Sarilumab in participants with Ankylosing Spondylitis (AS) using the assessment in AS working group criteria (ASAS) 20% response criteria (ASAS20)

Secondary objectives:

* to demonstrate that Sarilumab was effective on:

  * assessment of higher level of response \[ASAS 40% response criteria (ASAS40)\]
  * partial remission
  * disease activity
  * range of motion
  * Magnetic Resonance Imaging (MRI) of the spine
* to assess the safety and tolerability of Sarilumab in participants with AS as well as the pharmacokinetic profile of Sarilumab in participants with AS

Detailed description: The duration of participation in this study for each participant was approximately 22 weeks; including up to 4 weeks screening period, 12-weeks double-blind treatment period and 6-weeks safety follow-up period.

Eligibility criteria: Inclusion criteria:

* Diagnosis of AS according to the New York modified criteria
* Participants must had an adequate trial of at least 2 different Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) taken for at least 2 weeks in each case and, on a stable dose for ≥2 weeks or be intolerant to NSAIDs
* Participants must had active AS for ≥3 months before screening and active disease must be present at screening and at baseline; Active AS being defined by:

  * Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥4 (Numerical Rating Scale 0-10)
  * Total back pain score ≥4 (Numerical Rating Scale 0-10)

Participants treated with corticosteroid must be on a stable dose for ≥2 weeks prior to baseline

Participants treated with the Disease Modifying Anti-Rheumatic Drugs (DMARDs) hydroxychloroquine, sulfasalazine and methotrexate (MTX) must be on stable dose ≥12 weeks prior to baseline

Exclusion criteria:

* \<18 years old or ≥75 years old
* Complete fusion of the spine
* Past history of non response to any anti-Tumor Necrosis Factors (TNFs) treatment or non response to any other biological treatment for AS
* Any past or current treatment with anti-TNF's or any biological agent within 3 months prior to screening
* Treatment with DMARDs except for hydroxychloroquine, sulfasalazine and MTX
* MTX \>25 mg/week
* hydroxychloroquine \>400 mg/day
* Sulfasalazine \>3 g/day
* Treatment with oral prednisone or equivalent corticosteroids \>10 mg/day within 6 weeks prior to screening
* Use of intramuscular or intra-articular corticosteroids within the last 4 weeks before screening
* Previous treatment with cyclosporine, azathioprine

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

Primary outcomes:
measure: Percentage of Participants Who Achieved 20% Response According to the Assessment in Ankylosing Spondylitis (AS) Working Group Criteria for Response (ASAS20) at Week 12
timeFrame: Baseline to Week 12 (Last Observation Carried Forward [LOCF])
Secondary outcomes:
measure: Percentage of Participants Who Achieved 40% Response According to the Assessment in AS Working Group Criteria for Response (ASAS40) at Week 12
timeFrame: Baseline to Week 12 (LOCF)
measure: Percentage of Participants Who Achieved Partial Remission According to the Assessment in AS Working Group Criteria for Response (ASAS) at Week 12
timeFrame: Baseline to Week 12 (LOCF)
measure: Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 12
timeFrame: Baseline, Week 12 (LOCF)
measure: Change From Baseline in BASDAI Score at Week 12
timeFrame: Baseline, Week 12 (LOCF)
measure: Change From Baseline in Range of Motion Assessed by the Bath AS Metrology Index (BASMI) at Week 12
timeFrame: Baseline, Week 12 (LOCF)
measure: Change From Baseline in Magnetic Resonance Imaging (MRI) Score of the Spine Assessed by the Berlin Modification of the AS Spine MRI-active (ASspiMRI-a) Score at Week 12
timeFrame: Baseline, Week 12
measure: Percentage of Participants Who Achieved ASAS 5/6 Improvement Criteria at Week 12
timeFrame: Baseline to Week 12 (LOCF)
measure: Change From Baseline in Chest Expansion at Week 12
timeFrame: Baseline, Week 12 (LOCF)
measure: Change From Baseline in Swollen Joint Index at Week 12
timeFrame: Baseline, Week 12 (LOCF)
measure: Change From Baseline in Hs-CRP at Week 12
timeFrame: Baseline, Week 12 (LOCF)
measure: Change From Baseline in ASAS Individual Components at Week 12
timeFrame: Baseline, Week 12 (LOCF)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 840006
state: Alabama
city: Anaheim
country: United States
facility: Investigational Site Number 840033
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 840027
state: California
city: San Diego
country: United States
facility: Investigational Site Number 840007
state: California
city: San Francisco
country: United States
facility: Investigational Site Number 840013
state: California
city: Upland
country: United States
facility: Investigational Site Number 840017
state: California
city: Boca Raton
country: United States
facility: Investigational Site Number 840009
state: Florida
city: Naples
country: United States
facility: Investigational Site Number 840001
state: Florida
city: Orlando
country: United States
facility: Investigational Site Number 840032
state: Florida
city: Boise
country: United States
facility: Investigational Site Number 840015
state: Idaho
city: Rock Island
country: United States
facility: Investigational Site Number 840021
state: Illinois
city: Kansas City
country: United States
facility: Investigational Site Number 840018
state: Kansas
city: Wheaton
country: United States
facility: Investigational Site Number 840003
state: Maryland
city: Worcester
country: United States
facility: Investigational Site Number 840029
state: Massachusetts
city: Lansing
country: United States
facility: Investigational Site Number 840008
state: Michigan
city: Saint Louis
country: United States
facility: Investigational Site Number 840002
state: Missouri
city: Freehold
country: United States
facility: Investigational Site Number 840028
state: New Jersey
city: Albany
country: United States
facility: Investigational Site Number 840016
state: New York
city: Syracuse
country: United States
facility: Investigational Site Number 840036
state: New York
city: Toledo
country: United States
facility: Investigational Site Number 840010
state: Ohio
city: Oklahoma City
country: United States
facility: Investigational Site Number 840005
state: Oklahoma
city: Bethlehem
country: United States
facility: Investigational Site Number 840023
state: Pennsylvania
city: Duncansville
country: United States
facility: Investigational Site Number 840014
state: Pennsylvania
city: Dallas
country: United States
facility: Investigational Site Number 840004
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 840030
state: Texas
city: Chesapeake
country: United States
facility: Investigational Site Number 840034
state: Virginia
city: East Malvern
country: Australia
facility: Investigational Site Number 036001
city: Hobart
country: Australia
facility: Investigational Site Number 036003
city: Shenton Park
country: Australia
facility: Investigational Site Number 036004
city: Woolloongabba
country: Australia
facility: Investigational Site Number 036002
city: Graz
country: Austria
facility: Investigational Site Number 040001
city: Wien
country: Austria
facility: Investigational Site Number 040002
city: Brussels
country: Belgium
facility: Investigational Site Number 056003
city: Genk
country: Belgium
facility: Investigational Site Number 056005
city: Gent
country: Belgium
facility: Investigational Site Number 056001
city: Leuven
country: Belgium
facility: Investigational Site Number 056002
city: Liège
country: Belgium
facility: Investigational Site Number 056004
city: London
country: Canada
facility: Investigational Site Number 124007
city: Montreal
country: Canada
facility: Investigational Site Number 124004
city: Newmarket
country: Canada
facility: Investigational Site Number 124008
city: Pointe-Claire
country: Canada
facility: Investigational Site Number 124003
city: Quebec
country: Canada
facility: Investigational Site Number 124001
city: Saskatoon
country: Canada
facility: Investigational Site Number 124006
city: Toronto
country: Canada
facility: Investigational Site Number 124005
city: Trois-Rivières
country: Canada
facility: Investigational Site Number 124009
city: Vancouver
country: Canada
facility: Investigational Site Number 124002
city: Vancouver
country: Canada
facility: Investigational Site Number 124010
city: Brno
country: Czechia
facility: Investigational Site Number 203003
city: Hlucin
country: Czechia
facility: Investigational Site Number 203005
city: Hradec Kralove
country: Czechia
facility: Investigational Site Number 203002
city: Praha 2
country: Czechia
facility: Investigational Site Number 203001
city: Uherske Hradiste
country: Czechia
facility: Investigational Site Number 203004
city: Besancon
country: France
facility: Investigational Site Number 250001
city: Bordeaux
country: France
facility: Investigational Site Number 250005
city: Creteil Cedex
country: France
facility: Investigational Site Number 250002
city: Paris
country: France
facility: Investigational Site Number 250003
city: Berlin
country: Germany
facility: Investigational Site Number 276002
city: Erlangen
country: Germany
facility: Investigational Site Number 276004
city: Frankfurt Am Main
country: Germany
facility: Investigational Site Number 276003
city: Hamburg
country: Germany
facility: Investigational Site Number 276005
city: Herne
country: Germany
facility: Investigational Site Number 276001
city: Budapest
country: Hungary
facility: Investigational Site Number 348001
city: Debrecen
country: Hungary
facility: Investigational Site Number 348003
city: Sátoraljaújhely
country: Hungary
facility: Investigational Site Number 348005
city: Veszprém
country: Hungary
facility: Investigational Site Number 348004
city: Kaunas
country: Lithuania
facility: Investigational Site Number 440001
city: Vilnius
country: Lithuania
facility: Investigational Site Number 440002
city: Amsterdam
country: Netherlands
facility: Investigational Site Number 528001
city: Nijmegen
country: Netherlands
facility: Investigational Site Number 528002
city: Bialystok
country: Poland
facility: Investigational Site Number 616002
city: Krakow
country: Poland
facility: Investigational Site Number 616001
city: Lublin
country: Poland
facility: Investigational Site Number 616004
city: Torun
country: Poland
facility: Investigational Site Number 616005
city: Warszawa
country: Poland
facility: Investigational Site Number 616003
city: Barcelona
country: Spain
facility: Investigational Site Number 724005
city: La Coruña
country: Spain
facility: Investigational Site Number 724004
city: Madrid
country: Spain
facility: Investigational Site Number 724002
city: Sevilla
country: Spain
facility: Investigational Site Number 724001
city: Ankara
country: Turkey
facility: Investigational Site Number 792002
city: Izmir
country: Turkey
facility: Investigational Site Number 792001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Sieper J, Braun J, Kay J, Badalamenti S, Radin AR, Jiao L, Fiore S, Momtahen T, Yancopoulos GD, Stahl N, Inman RD. Sarilumab for the treatment of ankylosing spondylitis: results of a Phase II, randomised, double-blind, placebo-controlled study (ALIGN). Ann Rheum Dis. 2015 Jun;74(6):1051-7. doi: 10.1136/annrheumdis-2013-204963. Epub 2014 Feb 18.