Dose Ranging Study to Evaluate the Efficacy and Safety of SAR153191 (REGN88) in Patients With Ankylosing Spondylitis
- Registration Number
- NCT01061723
- Lead Sponsor
- Sanofi
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 301
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sarilumab 100 mg q2w Sarilumab Sarilumab 100 mg Subcutaneous (SC) injection alternating with placebo every other week (q2w) for 12 weeks. Sarilumab 150 mg q2w Placebo Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks. Sarilumab 200 mg q2w Placebo Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks. Sarilumab 150 mg q2w Sarilumab Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks. Placebo Placebo Placebo (for sarilumab) weekly (qw) for 12 weeks. Sarilumab 100 mg q2w Placebo Sarilumab 100 mg Subcutaneous (SC) injection alternating with placebo every other week (q2w) for 12 weeks. Sarilumab 200 mg q2w Sarilumab Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks. Sarilumab 150 mg qw Sarilumab Sarilumab 150 mg SC injection qw for 12 weeks. Sarilumab 100 mg qw Sarilumab Sarilumab 100 mg SC injection qw for 12 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Achieved 20% Response According to the Assessment in Ankylosing Spondylitis (AS) Working Group Criteria for Response (ASAS20) at Week 12 Baseline to Week 12 (Last Observation Carried Forward [LOCF]) Clinical response to treatment for ASAS20 was assessed according to ASAS20 criteria. Treatment response for ASAS20 was defined as an improvement by a decrease of ≥20% and ≥1unit on a 0 (no pain) - 10 (most severe pain) numerical rating scale (NRS) in at least 3 of the 4 ASAS improvement criteria (ASAS-IC) domains: assessment of physical function (measured by Bath Ankylosing Spondylitis Functional Index \[BASFI\]), back pain (0-10 NRS), participant global assessment (0-10 NRS) and inflammation (measured as the mean of the last 2 Bath Ankylosing Spondylitis Disease Activity Index \[BASDAI\] questions) and no worsening (increase in score) of ≥20% and ≥1 unit on a 0-10 NRS in the remaining 4th domain.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Who Achieved 40% Response According to the Assessment in AS Working Group Criteria for Response (ASAS40) at Week 12 Baseline to Week 12 (LOCF) Clinical response to treatment for ASAS40 was assessed according to ASAS40 criteria. Treatment response for ASAS40 was defined as an improvement by a decrease of ≥40% and ≥2 units on a 0 (no pain)-10 (most severe pain) NRS in at least 3 of the 4 ASAS-IC domains (participant global assessment, back pain, physical function and inflammation) and no worsening (increase in score) at all in the remaining 4th domain.
Percentage of Participants Who Achieved Partial Remission According to the Assessment in AS Working Group Criteria for Response (ASAS) at Week 12 Baseline to Week 12 (LOCF) Participants were classified as having achieved ASAS partial remission if they had a value ≤ 2 units on a 0 -10 NRS in each of the 4 domains: (participant global assessment, back pain, physical function and inflammation) of the ASAS-IC.
Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 12 Baseline, Week 12 (LOCF) ASDAS consists of five components: (Total back pain assessed by BASDAI question 2 on a 0 \[no pain\] - 10 \[most severe pain\] NRS, participant global of disease activity on a 0 \[none\] - 10 \[severe\] NRS, peripheral pain/swelling assessed by BASDAI question 3 on a 0 \[none\] - 10 \[most severe pain\] NRS, duration of morning stiffness assessed by BASDAI question 6 on a NRS from 0 \[0 hour\] - 10 \[2 or more hours\] and hs-CRP in mg/L). ASDAS score was calculated as follows: 0.121 x total back pain + 0.110 x participant global of disease activity + 0.073 x peripheral pain/swelling + 0.058 x duration of morning stiffness + 0.579 x ln(CRP + 1). The scores were categorized as: inactive disease (\< 1.3), moderate (1.3 - \< 2.1), high (2.1 - 3.5) and very high disease activity (\> 3.5).
Change From Baseline in BASDAI Score at Week 12 Baseline, Week 12 (LOCF) BASDAI comprises of a 0 (no pain) -10 (very severe pain) NRS, used to answer 6 questions (Q) related to symptoms of AS (fatigue/tiredness, neck, back or hip pain, pain / swelling in joints, discomfort in tender areas, morning stiffness duration and morning stiffness severity). The BASDAI total score was calculated by computing the mean of Q5 and Q6 and adding it to the sum of Q1 to Q4. This score was then divided by 5. BASDAI total score=Q1+Q2+Q3+Q4+\[Q5+Q6/2\]/5. The total BASDAI score ranges from 0=none to 10=severe, where lower score indicated less disease activity.
Change From Baseline in Range of Motion Assessed by the Bath AS Metrology Index (BASMI) at Week 12 Baseline, Week 12 (LOCF) The range of motion was measured by the BASMI (11-point scale) including chest expansion in cm. It composed of 5 clinical measurements associated with a score: tragus to wall distance, modified schober's test, lateral spinal flexion, intermalleolar distance and cervical rotation. BASMI score was calculated by dividing the total of the score by 5, and the score ranges from 0-10. Higher BASMI score indicates more severe limitation of movement.
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 Baseline, Week 12 ASspiMRI-a scoring system was used on all MRIs to score the level of the disease. MRIs were obtained using 1.0 or 1.5 Tesla scanners and phased array coils. Sagittal images of the upper (C2 to T10) and lower (T8 to S1) spine were used using both T1 weighted spin echo and fat saturated Short Tau Inversion Recovery (STIR) sequences. Each vertebral body unit was given an activity score based on the amount of bone marrow edema or erosion. Both T1 and STIR sequences were analyzed for change. Total spine ASspiMRI-a score in the Berlin modification range from 0 to 69 with higher scores indicating higher disease activity. A negative value in total spine ASspiMRI-a score change from baseline indicates an improvement from baseline. The higher the negative value the higher the reduction of inflammation.
Percentage of Participants Who Achieved ASAS 5/6 Improvement Criteria at Week 12 Baseline to Week 12 (LOCF) ASAS 5/6 responder had an improvement of 20% in 5 of 6 domains (physical function, back pain, participant global assessment, inflammation, spinal mobility and acute phase reactants) of ASAS-IC without deterioration in the 6th domain. Spinal mobility was assessed by the mean of the 5 BASMI scores on the 11-point scale (score ranges from 0-10) and the hs-CRP for the acute phase reactant.
Change From Baseline in Chest Expansion at Week 12 Baseline, Week 12 (LOCF) The difference between maximal inspiration and expiration to the nearest 0.1 cm was recorded. The best of 2 tries were recorded.
Change From Baseline in Swollen Joint Index at Week 12 Baseline, Week 12 (LOCF) 44 swollen joints were examined including sternal, clavicular, elbow, shoulder, wrist, knee, metacarpophalangian, interphalangian, metatarpophalangian and metatarsophalangeal joints.
Change From Baseline in Hs-CRP at Week 12 Baseline, Week 12 (LOCF) Participant's blood samples were collected at screening, baseline before dosing and at every visit to evaluate the level of hs-CRP. The hs-CRP is a protein marker in the blood associated with inflammation with higher values indicating a greater degree of inflammation.
Change From Baseline in ASAS Individual Components at Week 12 Baseline, Week 12 (LOCF) ASAS consists of 4 individual components: Participant global assessment to assess the disease activity over the last week on a 0 (no pain) - 10 (severe pain) NRS; back pain which consist of the mean of the nocturnal back pain and the total back pain at every visit on a 0 (no pain) - 10 (most severe pain) NRS; inflammation measured as the mean of the last 2 BASDAI questions (intensity and duration of morning stiffness) and physical function measured as mean of 10 scores of BASFI at every visit on 0 (easy) -10 (impossible) NRS. Lower score corresponds to a better functioning.
Trial Locations
- Locations (80)
Investigational Site Number 840027
🇺🇸Los Angeles, California, United States
Investigational Site Number 840009
🇺🇸Boca Raton, Florida, United States
Investigational Site Number 840015
🇺🇸Boise, Idaho, United States
Investigational Site Number 840036
🇺🇸Syracuse, New York, United States
Investigational Site Number 056004
🇧🇪Liège, Belgium
Investigational Site Number 348001
🇭🇺Budapest, Hungary
Investigational Site Number 616001
🇵🇱Krakow, Poland
Investigational Site Number 840007
🇺🇸San Diego, California, United States
Investigational Site Number 840033
🇺🇸Anaheim, California, United States
Investigational Site Number 840001
🇺🇸Naples, Florida, United States
Investigational Site Number 840021
🇺🇸Rock Island, Illinois, United States
Investigational Site Number 840008
🇺🇸Lansing, Michigan, United States
Investigational Site Number 840003
🇺🇸Wheaton, Maryland, United States
Investigational Site Number 840028
🇺🇸Freehold, New Jersey, United States
Investigational Site Number 840016
🇺🇸Albany, New York, United States
Investigational Site Number 840004
🇺🇸Dallas, Texas, United States
Investigational Site Number 840023
🇺🇸Bethlehem, Pennsylvania, United States
Investigational Site Number 840030
🇺🇸Houston, Texas, United States
Investigational Site Number 840034
🇺🇸Chesapeake, Virginia, United States
Investigational Site Number 036001
🇦🇺East Malvern, Australia
Investigational Site Number 036004
🇦🇺Shenton Park, Australia
Investigational Site Number 036003
🇦🇺Hobart, Australia
Investigational Site Number 036002
🇦🇺Woolloongabba, Australia
Investigational Site Number 056003
🇧🇪Brussels, Belgium
Investigational Site Number 040001
🇦🇹Graz, Austria
Investigational Site Number 040002
🇦🇹Wien, Austria
Investigational Site Number 124004
🇨🇦Montreal, Canada
Investigational Site Number 124007
🇨🇦London, Canada
Investigational Site Number 056002
🇧🇪Leuven, Belgium
Investigational Site Number 124008
🇨🇦Newmarket, Canada
Investigational Site Number 124003
🇨🇦Pointe-Claire, Canada
Investigational Site Number 124001
🇨🇦Quebec, Canada
Investigational Site Number 124006
🇨🇦Saskatoon, Canada
Investigational Site Number 203005
🇨🇿Hlucin, Czechia
Investigational Site Number 203003
🇨🇿Brno, Czechia
Investigational Site Number 203002
🇨🇿Hradec Kralove, Czechia
Investigational Site Number 203001
🇨🇿Praha 2, Czechia
Investigational Site Number 250005
🇫🇷Bordeaux, France
Investigational Site Number 276002
🇩🇪Berlin, Germany
Investigational Site Number 276001
🇩🇪Herne, Germany
Investigational Site Number 348003
🇭🇺Debrecen, Hungary
Investigational Site Number 348005
🇭🇺Sátoraljaújhely, Hungary
Investigational Site Number 348004
🇭🇺Veszprém, Hungary
Investigational Site Number 440002
🇱🇹Vilnius, Lithuania
Investigational Site Number 440001
🇱🇹Kaunas, Lithuania
Investigational Site Number 528002
🇳🇱Nijmegen, Netherlands
Investigational Site Number 528001
🇳🇱Amsterdam, Netherlands
Investigational Site Number 616002
🇵🇱Bialystok, Poland
Investigational Site Number 724004
🇪🇸La Coruña, Spain
Investigational Site Number 724001
🇪🇸Sevilla, Spain
Investigational Site Number 792001
🇹🇷Izmir, Turkey
Investigational Site Number 124002
🇨🇦Vancouver, Canada
Investigational Site Number 840013
🇺🇸San Francisco, California, United States
Investigational Site Number 840005
🇺🇸Oklahoma City, Oklahoma, United States
Investigational Site Number 840006
🇺🇸Birmingham, Alabama, United States
Investigational Site Number 840017
🇺🇸Upland, California, United States
Investigational Site Number 840029
🇺🇸Worcester, Massachusetts, United States
Investigational Site Number 840018
🇺🇸Kansas City, Kansas, United States
Investigational Site Number 840014
🇺🇸Duncansville, Pennsylvania, United States
Investigational Site Number 840002
🇺🇸Saint Louis, Missouri, United States
Investigational Site Number 056001
🇧🇪Gent, Belgium
Investigational Site Number 056005
🇧🇪Genk, Belgium
Investigational Site Number 124005
🇨🇦Toronto, Canada
Investigational Site Number 124010
🇨🇦Vancouver, Canada
Investigational Site Number 203004
🇨🇿Uherske Hradiste, Czechia
Investigational Site Number 250001
🇫🇷Besancon, France
Investigational Site Number 250002
🇫🇷Creteil Cedex, France
Investigational Site Number 250003
🇫🇷Paris, France
Investigational Site Number 276005
🇩🇪Hamburg, Germany
Investigational Site Number 276004
🇩🇪Erlangen, Germany
Investigational Site Number 276003
🇩🇪Frankfurt Am Main, Germany
Investigational Site Number 792002
🇹🇷Ankara, Turkey
Investigational Site Number 616003
🇵🇱Warszawa, Poland
Investigational Site Number 616004
🇵🇱Lublin, Poland
Investigational Site Number 616005
🇵🇱Torun, Poland
Investigational Site Number 724002
🇪🇸Madrid, Spain
Investigational Site Number 724005
🇪🇸Barcelona, Spain
Investigational Site Number 840010
🇺🇸Toledo, Ohio, United States
Investigational Site Number 124009
🇨🇦Trois-Rivières, Canada
Investigational Site Number 840032
🇺🇸Orlando, Florida, United States