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Dose Ranging Study to Evaluate the Efficacy and Safety of SAR153191 (REGN88) in Patients With Ankylosing Spondylitis (ALIGN)

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ClinicalTrials.gov Identifier: NCT01061723
Recruitment Status : Completed
First Posted : February 3, 2010
Results First Posted : August 8, 2017
Last Update Posted : August 8, 2017
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Ankylosing Spondylitis
Interventions Drug: Sarilumab
Drug: Placebo
Enrollment 301
Recruitment Details The study was conducted at 68 centers in Europe, Canada and the United States. A total of 563 participants were screened between 04 February 2010 and 24 February 2011. Of 563 participants, 301 were randomized and 300 were treated.
Pre-assignment Details Participants were randomized in 1:1:1:1:1:1 ratio for Placebo and Sarilumab (100 mg weekly [qw]; 150 mg qw; 100 mg every other week [q2w]; 150 mg q2w and 200 mg q2w) with screening high-sensitivity C-Reactive Protein (hs-CRP) (≤1.5 mg/L or >1.5 mg/L) and region as stratification factors.
Arm/Group Title Placebo Sarilumab 100 mg q2w Sarilumab 150 mg q2w Sarilumab 100 mg qw Sarilumab 200 mg q2w Sarilumab 150 mg qw
Hide Arm/Group Description Placebo (for sarilumab) qw for 12 weeks. Sarilumab 100 mg subcutaneous (SC) injection alternating with placebo q2w for 12 weeks. Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks. Sarilumab 100 mg SC injection qw for 12 weeks. Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks. Sarilumab 150 mg SC injection qw for 12 weeks.
Period Title: Overall Study
Started 50 49 50 52 50 50
Treated 50 49 50 52 50 49
Completed 46 43 40 44 47 41
Not Completed 4 6 10 8 3 9
Reason Not Completed
Adverse Event             0             2             5             5             2             6
Lack of Efficacy             2             3             4             2             1             1
Randomized but not treated             0             0             0             0             0             1
Other than specified above             2             1             1             1             0             1
Arm/Group Title Placebo Sarilumab 100 mg q2w Sarilumab 150 mg q2w Sarilumab 100 mg qw Sarilumab 200 mg q2w Sarilumab 150 mg qw Total
Hide Arm/Group Description Placebo (for sarilumab) qw for 12 weeks. Sarilumab 100 mg SC injection alternating with placebo q2w for 12 weeks. Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks. Sarilumab 100 mg SC injection qw for 12 weeks. Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks. Sarilumab 150 mg SC injection qw for 12 weeks. Total of all reporting groups
Overall Number of Baseline Participants 50 49 50 52 50 50 301
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 50 participants 49 participants 50 participants 52 participants 50 participants 50 participants 301 participants
40.3  (11.7) 42.4  (10.8) 43.0  (11.3) 40.4  (11.5) 37.2  (10.4) 41.1  (11.1) 40.7  (11.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants 49 participants 50 participants 52 participants 50 participants 50 participants 301 participants
Female
12
  24.0%
19
  38.8%
16
  32.0%
15
  28.8%
10
  20.0%
11
  22.0%
83
  27.6%
Male
38
  76.0%
30
  61.2%
34
  68.0%
37
  71.2%
40
  80.0%
39
  78.0%
218
  72.4%
1.Primary Outcome
Title Percentage of Participants Who Achieved 20% Response According to the Assessment in Ankylosing Spondylitis (AS) Working Group Criteria for Response (ASAS20) at Week 12
Hide Description 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.
Time Frame Baseline to Week 12 (Last Observation Carried Forward [LOCF])
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population included all randomized participants. Missing data was imputed using LOCF.
Arm/Group Title Placebo Sarilumab 100 mg q2w Sarilumab 150 mg q2w Sarilumab 100 mg qw Sarilumab 200 mg q2w Sarilumab 150 mg qw
Hide Arm/Group Description:
Placebo (for sarilumab) qw for 12 weeks.
Sarilumab 100 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 100 mg SC injection qw for 12 weeks.
Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection qw for 12 weeks.
Overall Number of Participants Analyzed 50 49 50 52 50 50
Measure Type: Number
Unit of Measure: percentage of participants
24.0 24.5 30.0 19.2 30.0 38.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Sarilumab 100 mg q2w
Comments Sarilumab group was compared to placebo group. Analysis was performed using two-sided Cochran-Mantel-Haenszel test. Pairwise comparisons of the response rates between each dose of sarilumab and placebo were derived.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.966
Comments Threshold for significance = 0.05
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
0.4 to 2.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Sarilumab 150 mg q2w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.467
Comments Threshold for significance = 0.05
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
0.6 to 3.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Sarilumab 100 mg qw
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.559
Comments Threshold for significance = 0.05
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
0.3 to 1.9
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Sarilumab 200 mg q2w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.496
Comments Threshold for significance = 0.05
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
0.6 to 3.4
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Sarilumab 150 mg qw
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.143
Comments Threshold for significance = 0.05
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.8
Confidence Interval (2-Sided) 95%
0.8 to 4.2
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants Who Achieved 40% Response According to the Assessment in AS Working Group Criteria for Response (ASAS40) at Week 12
Hide Description 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.
Time Frame Baseline to Week 12 (LOCF)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Missing data was imputed using LOCF.
Arm/Group Title Placebo Sarilumab 100 mg q2w Sarilumab 150 mg q2w Sarilumab 100 mg qw Sarilumab 200 mg q2w Sarilumab 150 mg qw
Hide Arm/Group Description:
Placebo (for sarilumab) qw for 12 weeks.
Sarilumab 100 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 100 mg SC injection qw for 12 weeks.
Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection qw for 12 weeks.
Overall Number of Participants Analyzed 50 49 50 52 50 50
Measure Type: Number
Unit of Measure: percentage of participants
8.0 14.3 16.0 5.8 18.0 20.0
3.Secondary Outcome
Title Percentage of Participants Who Achieved Partial Remission According to the Assessment in AS Working Group Criteria for Response (ASAS) at Week 12
Hide Description 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.
Time Frame Baseline to Week 12 (LOCF)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Missing data was imputed using LOCF.
Arm/Group Title Placebo Sarilumab 100 mg q2w Sarilumab 150 mg q2w Sarilumab 100 mg qw Sarilumab 200 mg q2w Sarilumab 150 mg qw
Hide Arm/Group Description:
Placebo (for sarilumab) qw for 12 weeks.
Sarilumab 100 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 100 mg SC injection qw for 12 weeks.
Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection qw for 12 weeks.
Overall Number of Participants Analyzed 50 49 50 52 50 50
Measure Type: Number
Unit of Measure: percentage of participants
2.0 8.2 2.0 1.9 2.0 8.0
4.Secondary Outcome
Title Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 12
Hide Description 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).
Time Frame Baseline, Week 12 (LOCF)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Missing data was imputed using LOCF. Number of participants analyzed = participants with ASDAS score assessment at specified time-points.
Arm/Group Title Placebo Sarilumab 100 mg q2w Sarilumab 150 mg q2w Sarilumab 100 mg qw Sarilumab 200 mg q2w Sarilumab 150 mg qw
Hide Arm/Group Description:
Placebo (for sarilumab) qw for 12 weeks.
Sarilumab 100 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 100 mg SC injection qw for 12 weeks.
Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection qw for 12 weeks.
Overall Number of Participants Analyzed 49 47 50 51 50 49
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.4  (0.7) -0.5  (0.9) -0.8  (1.2) -1.1  (0.8) -1.2  (0.9) -1.6  (0.9)
5.Secondary Outcome
Title Change From Baseline in BASDAI Score at Week 12
Hide Description 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.
Time Frame Baseline, Week 12 (LOCF)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Missing data was imputed using LOCF. Number of participants analyzed = participants with BASDAI score assessment at specified time-points.
Arm/Group Title Placebo Sarilumab 100 mg q2w Sarilumab 150 mg q2w Sarilumab 100 mg qw Sarilumab 200 mg q2w Sarilumab 150 mg qw
Hide Arm/Group Description:
Placebo (for sarilumab) qw for 12 weeks.
Sarilumab 100 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 100 mg SC injection qw for 12 weeks.
Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection qw for 12 weeks.
Overall Number of Participants Analyzed 49 48 50 51 50 49
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.9  (1.7) -0.8  (1.9) -1.1  (2.0) -0.4  (1.4) -0.9  (1.8) -1.2  (1.8)
6.Secondary Outcome
Title Change From Baseline in Range of Motion Assessed by the Bath AS Metrology Index (BASMI) at Week 12
Hide Description 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.
Time Frame Baseline, Week 12 (LOCF)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Missing data was imputed using LOCF. Number of participants analyzed=participants with BASMI score assessment at specified time-points.
Arm/Group Title Placebo Sarilumab 100 mg q2w Sarilumab 150 mg q2w Sarilumab 100 mg qw Sarilumab 200 mg q2w Sarilumab 150 mg qw
Hide Arm/Group Description:
Placebo (for sarilumab) qw for 12 weeks.
Sarilumab 100 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 100 mg SC injection qw for 12 weeks.
Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection qw for 12 weeks.
Overall Number of Participants Analyzed 49 48 50 51 50 49
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.2  (0.8) -0.2  (0.9) -0.2  (0.8) -0.4  (0.9) -0.1  (0.8) -0.2  (0.7)
7.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Baseline, Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Number of participants analyzed = participants with ASspiMRI-a assessment at specified time-points.
Arm/Group Title Placebo Sarilumab 100 mg q2w Sarilumab 150 mg q2w Sarilumab 100 mg qw Sarilumab 200 mg q2w Sarilumab 150 mg qw
Hide Arm/Group Description:
Placebo (for sarilumab) qw for 12 weeks.
Sarilumab 100 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 100 mg SC injection qw for 12 weeks.
Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection qw for 12 weeks.
Overall Number of Participants Analyzed 45 42 44 47 46 44
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.5  (2.2) -0.5  (1.8) -0.1  (3.4) 0.1  (2.4) -0.3  (3.3) 0.3  (3.3)
8.Secondary Outcome
Title Percentage of Participants Who Achieved ASAS 5/6 Improvement Criteria at Week 12
Hide Description 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.
Time Frame Baseline to Week 12 (LOCF)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Missing data was imputed using LOCF.
Arm/Group Title Placebo Sarilumab 100 mg q2w Sarilumab 150 mg q2w Sarilumab 100 mg qw Sarilumab 200 mg q2w Sarilumab 150 mg qw
Hide Arm/Group Description:
Placebo (for sarilumab) qw for 12 weeks.
Sarilumab 100 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 100 mg SC injection qw for 12 weeks.
Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection qw for 12 weeks.
Overall Number of Participants Analyzed 50 49 50 52 50 50
Measure Type: Number
Unit of Measure: percentage of participants
6.0 12.2 10.0 13.5 14.0 32.0
9.Secondary Outcome
Title Change From Baseline in Chest Expansion at Week 12
Hide Description The difference between maximal inspiration and expiration to the nearest 0.1 cm was recorded. The best of 2 tries were recorded.
Time Frame Baseline, Week 12 (LOCF)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Missing data was imputed using LOCF. Number of participants analyzed = participants with chest expansion assessment at specified time-points.
Arm/Group Title Placebo Sarilumab 100 mg q2w Sarilumab 150 mg q2w Sarilumab 100 mg qw Sarilumab 200 mg q2w Sarilumab 150 mg qw
Hide Arm/Group Description:
Placebo (for sarilumab) qw for 12 weeks.
Sarilumab 100 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 100 mg SC injection qw for 12 weeks.
Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection qw for 12 weeks.
Overall Number of Participants Analyzed 49 47 49 51 50 49
Mean (Standard Deviation)
Unit of Measure: cm
0.2  (1.0) 0.2  (1.2) 0.0  (1.2) -0.1  (0.9) 0.1  (1.3) 0.3  (1.3)
10.Secondary Outcome
Title Change From Baseline in Swollen Joint Index at Week 12
Hide Description 44 swollen joints were examined including sternal, clavicular, elbow, shoulder, wrist, knee, metacarpophalangian, interphalangian, metatarpophalangian and metatarsophalangeal joints.
Time Frame Baseline, Week 12 (LOCF)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Missing data was imputed using LOCF. Number of participants analyzed = participants with swollen joint count assessment at specified time-points.
Arm/Group Title Placebo Sarilumab 100 mg q2w Sarilumab 150 mg q2w Sarilumab 100 mg qw Sarilumab 200 mg q2w Sarilumab 150 mg qw
Hide Arm/Group Description:
Placebo (for sarilumab) qw for 12 weeks.
Sarilumab 100 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 100 mg SC injection qw for 12 weeks.
Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection qw for 12 weeks.
Overall Number of Participants Analyzed 50 48 50 51 50 49
Mean (Standard Deviation)
Unit of Measure: Joints
-0.4  (1.1) -0.8  (3.1) -0.3  (1.9) -0.3  (2.4) -0.4  (1.6) -0.2  (7.3)
11.Secondary Outcome
Title Change From Baseline in Hs-CRP at Week 12
Hide Description 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.
Time Frame Baseline, Week 12 (LOCF)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Missing data was imputed using LOCF. Number of participants analyzed = participants with Hs-CRP assessment at specified time-points.
Arm/Group Title Placebo Sarilumab 100 mg q2w Sarilumab 150 mg q2w Sarilumab 100 mg qw Sarilumab 200 mg q2w Sarilumab 150 mg qw
Hide Arm/Group Description:
Placebo (for sarilumab) qw for 12 weeks.
Sarilumab 100 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 100 mg SC injection qw for 12 weeks.
Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection qw for 12 weeks.
Overall Number of Participants Analyzed 50 48 50 51 50 49
Mean (Standard Deviation)
Unit of Measure: mg/dL
-3.7  (19.1) -1.2  (17.9) -5.8  (27.6) -13.5  (20.3) -11.5  (17.5) -14.3  (15.3)
12.Secondary Outcome
Title Change From Baseline in ASAS Individual Components at Week 12
Hide Description 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.
Time Frame Baseline, Week 12 (LOCF)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Missing data was imputed using LOCF. Number of participants analyzed = participants with ASAS assessment at specified time-points.
Arm/Group Title Placebo Sarilumab 100mg q2w Sarilumab 150mg q2w Sarilumab 100mg qw Sarilumab 200mg q2w Sarilumab 150mg qw
Hide Arm/Group Description:
Placebo (for sarilumab) qw for 12 weeks.
Sarilumab 100 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 100 mg SC injection qw for 12 weeks.
Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks.
Sarilumab 150 mg SC injection qw for 12 weeks.
Overall Number of Participants Analyzed 49 48 50 51 50 49
Mean (Standard Deviation)
Unit of Measure: units on a scale
Participant global assessment -1.0  (1.9) -1.1  (2.3) -0.8  (2.3) -0.4  (2.2) -0.9  (2.2) -1.6  (2.0)
Back pain -0.8  (1.8) -1.3  (2.2) -1.2  (2.4) -0.5  (1.8) -0.9  (2.2) -1.6  (2.1)
Inflammation -1.4  (1.8) -0.8  (2.0) -1.1  (2.0) -0.7  (2.1) -1.0  (1.9) -1.8  (2.3)
Physical function -0.6  (1.2) -0.5  (1.7) -0.4  (2.0) -0.1  (1.4) -0.6  (1.9) -1.1  (1.9)
Time Frame All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Week 18) regardless of seriousness or relationship to investigational product
Adverse Event Reporting Description Reported adverse events are treatment-emergent adverse events that is AEs that developed/worsened during ‘on treatment period’ (time from first dose injection of double-blind study to end of 6-week follow-up period). Safety population included all randomized participants who received at least one dose of the study medication.
 
Arm/Group Title Placebo SAR153191 100 mg q2w SAR153191 150 mg q2w SAR153191 100 mg qw SAR153191 200 mg q2w SAR153191 150 mg qw
Hide Arm/Group Description Placebo (for sarilumab) qw for 12 weeks. Sarilumab 100 mg SC injection alternating with placebo q2w for 12 weeks. Sarilumab 150 mg SC injection alternating with placebo q2w for 12 weeks. Included a participant randomized to sarilumab 200 mg q2w who received sarilumab 150 mg q2w in error. Sarilumab 100 mg SC injection qw for 12 weeks. Sarilumab 200 mg SC injection alternating with placebo q2w for 12 weeks. Excluded a participant randomized to sarilumab 200 mg q2w who received sarilumab 150 mg q2w in error. Sarilumab 150 mg SC injection qw for 12 weeks.
All-Cause Mortality
Placebo SAR153191 100 mg q2w SAR153191 150 mg q2w SAR153191 100 mg qw SAR153191 200 mg q2w SAR153191 150 mg qw
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo SAR153191 100 mg q2w SAR153191 150 mg q2w SAR153191 100 mg qw SAR153191 200 mg q2w SAR153191 150 mg qw
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/50 (0.00%)   1/49 (2.04%)   4/51 (7.84%)   1/52 (1.92%)   0/49 (0.00%)   1/49 (2.04%) 
Blood and lymphatic system disorders             
Neutropenia  1  0/50 (0.00%)  0/49 (0.00%)  1/51 (1.96%)  0/52 (0.00%)  0/49 (0.00%)  0/49 (0.00%) 
Cardiac disorders             
Myocardial ischemia  1  0/50 (0.00%)  0/49 (0.00%)  1/51 (1.96%)  0/52 (0.00%)  0/49 (0.00%)  0/49 (0.00%) 
General disorders             
Pain  1  0/50 (0.00%)  0/49 (0.00%)  1/51 (1.96%)  0/52 (0.00%)  0/49 (0.00%)  0/49 (0.00%) 
Infections and infestations             
Helicobacter gastritis  1  0/50 (0.00%)  0/49 (0.00%)  0/51 (0.00%)  1/52 (1.92%)  0/49 (0.00%)  0/49 (0.00%) 
Investigations             
Alanine aminotransferase increased  1  0/50 (0.00%)  0/49 (0.00%)  1/51 (1.96%)  0/52 (0.00%)  0/49 (0.00%)  0/49 (0.00%) 
False positive tuberculosis test  1  0/50 (0.00%)  0/49 (0.00%)  0/51 (0.00%)  0/52 (0.00%)  0/49 (0.00%)  1/49 (2.04%) 
Nervous system disorders             
Epilepsy  1  0/50 (0.00%)  1/49 (2.04%)  0/51 (0.00%)  0/52 (0.00%)  0/49 (0.00%)  0/49 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo SAR153191 100 mg q2w SAR153191 150 mg q2w SAR153191 100 mg qw SAR153191 200 mg q2w SAR153191 150 mg qw
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/50 (14.00%)   18/49 (36.73%)   23/51 (45.10%)   22/52 (42.31%)   19/49 (38.78%)   22/49 (44.90%) 
Blood and lymphatic system disorders             
Neutropenia  1  0/50 (0.00%)  0/49 (0.00%)  6/51 (11.76%)  2/52 (3.85%)  4/49 (8.16%)  8/49 (16.33%) 
Gastrointestinal disorders             
Abdominal pain  1  0/50 (0.00%)  3/49 (6.12%)  3/51 (5.88%)  1/52 (1.92%)  0/49 (0.00%)  0/49 (0.00%) 
Aphthous stomatitis  1  1/50 (2.00%)  3/49 (6.12%)  3/51 (5.88%)  2/52 (3.85%)  3/49 (6.12%)  1/49 (2.04%) 
Diarrhea  1  1/50 (2.00%)  2/49 (4.08%)  5/51 (9.80%)  0/52 (0.00%)  2/49 (4.08%)  0/49 (0.00%) 
General disorders             
Fatigue  1  0/50 (0.00%)  3/49 (6.12%)  2/51 (3.92%)  0/52 (0.00%)  0/49 (0.00%)  0/49 (0.00%) 
Injection site erythema  1  0/50 (0.00%)  1/49 (2.04%)  0/51 (0.00%)  3/52 (5.77%)  1/49 (2.04%)  1/49 (2.04%) 
Injection site pruritus  1  0/50 (0.00%)  0/49 (0.00%)  1/51 (1.96%)  3/52 (5.77%)  0/49 (0.00%)  1/49 (2.04%) 
Injection site reaction  1  0/50 (0.00%)  3/49 (6.12%)  2/51 (3.92%)  2/52 (3.85%)  1/49 (2.04%)  2/49 (4.08%) 
Infections and infestations             
Nasopharyngitis  1  1/50 (2.00%)  2/49 (4.08%)  2/51 (3.92%)  1/52 (1.92%)  2/49 (4.08%)  3/49 (6.12%) 
Upper respiratory tract infection  1  4/50 (8.00%)  1/49 (2.04%)  2/51 (3.92%)  7/52 (13.46%)  3/49 (6.12%)  4/49 (8.16%) 
Viral infection  1  0/50 (0.00%)  0/49 (0.00%)  3/51 (5.88%)  0/52 (0.00%)  0/49 (0.00%)  0/49 (0.00%) 
Injury, poisoning and procedural complications             
Accidental overdose  1  2/50 (4.00%)  2/49 (4.08%)  2/51 (3.92%)  2/52 (3.85%)  3/49 (6.12%)  1/49 (2.04%) 
Investigations             
Alanine aminotransferase increased  1  0/50 (0.00%)  0/49 (0.00%)  0/51 (0.00%)  4/52 (7.69%)  4/49 (8.16%)  1/49 (2.04%) 
Aspartate aminotransferase increased  1  0/50 (0.00%)  0/49 (0.00%)  0/51 (0.00%)  3/52 (5.77%)  1/49 (2.04%)  0/49 (0.00%) 
Musculoskeletal and connective tissue disorders             
Musculoskeletal pain  1  0/50 (0.00%)  1/49 (2.04%)  0/51 (0.00%)  0/52 (0.00%)  3/49 (6.12%)  1/49 (2.04%) 
Nervous system disorders             
Headache  1  0/50 (0.00%)  4/49 (8.16%)  2/51 (3.92%)  0/52 (0.00%)  2/49 (4.08%)  1/49 (2.04%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra 14.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
Name/Title: Trial Transparency Team
Organization: Sanofi
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01061723     History of Changes
Other Study ID Numbers: DRI11073
2009-016068-35 ( EudraCT Number )
First Submitted: February 2, 2010
First Posted: February 3, 2010
Results First Submitted: May 24, 2017
Results First Posted: August 8, 2017
Last Update Posted: August 8, 2017