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Trial record 1 of 1 for:    NCT01900431
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Phase II Study to Analyze Sarilumab in Non-Infectious Uveitis (SARILNIUSATURN)

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ClinicalTrials.gov Identifier: NCT01900431
Recruitment Status : Completed
First Posted : July 16, 2013
Results First Posted : June 20, 2017
Last Update Posted : June 20, 2017
Sponsor:
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Uveitis
Interventions Drug: Sarilumab
Drug: Prednisone
Drug: Methotrexate
Drug: Folic/folinic acid
Other: Placebo (for Sarilumab)
Enrollment 58
Recruitment Details The study was conducted at 18 centers in 6 countries. A total of 82 participants were screened between 30 October 2013 and 17 March 2015 of whom 58 participants were randomized and 24 were screen failures. Screen failures were mainly due to exclusion criteria met.
Pre-assignment Details Participants were randomized in 2:1 ratio (Sarilumab:Placebo) and treated for 16 weeks during principal treatment period (Part A), 30 responders treated up to Week 50 with same dose during extension treatment period (Part B) while 10 non-responders and 11 participants (not completed Part A) treated with open label treatment up to Week 50 (Part C).
Arm/Group Title Placebo Sarilumab 200 mg q2w Sarilumab 200 mg q2w (Open-Label Treatment)
Hide Arm/Group Description Placebo (for Sarilumab) subcutaneous (SC) injection every 2 weeks (q2w) for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with Methotrexate (MTX) 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B). Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B). Non-responders and non-completers observed in Part A were treated with Sarilumab 200 mg SC injection q2w for 34 weeks as open-label treatment in open-label treatment period (Part C) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Period Title: Principal Treatment Period (Part A)
Started 20 38 0
Completed 13 [1] 28 [2] 0
Not Completed 7 10 0
Reason Not Completed
Adverse Event             1             3             0
Lack of Efficacy             6             6             0
Other than specified above             0             1             0
[1]
8 responders entered Part B and 5 non-responders entered Part C.
[2]
22 responders entered Part B, 5 non-responders entered Part C, 1 discontinued the study.
Period Title: Extended Treatment Period (Part B)
Started 8 22 0
Completed 7 12 0
Not Completed 1 10 0
Reason Not Completed
Adverse Event             0             2             0
Lack of Efficacy             1             7             0
Other than specified above             0             1             0
Period Title: Open-Label Treatment Period (Part C)
Started 0 0 21 [1]
Completed 0 0 13
Not Completed 0 0 8
Reason Not Completed
Adverse Event             0             0             2
Lack of Efficacy             0             0             3
Withdrawal by Subject             0             0             3
[1]
10 non-responders (5 Placebo, 5 Sarilumab) & 11 non-completers (6 Placebo, 5 Sarilumab) from Part A.
Arm/Group Title Placebo Sarilumab 200 mg q2w Total
Hide Arm/Group Description Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B) and non-responders were proposed to be treated with open-label Sarilumab 200 mg q2w in open-label treatment period (Part-C). Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B) and non-responders were proposed to be treated with open-label Sarilumab 200 mg q2w in open-label treatment period (Part-C). Total of all reporting groups
Overall Number of Baseline Participants 20 38 58
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants 38 participants 58 participants
41.5  (13.0) 39.3  (15.3) 40.0  (14.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 38 participants 58 participants
Female
13
  65.0%
23
  60.5%
36
  62.1%
Male
7
  35.0%
15
  39.5%
22
  37.9%
1.Primary Outcome
Title Percentage of Participants With at Least 2-step Reduction in Vitreous Haze (VH) or Prednisone Dose <10 mg/Day at Week 16
Hide Description At least 2-step reduction in VH per central review from baseline was evaluated on Miami 9-step scale. VH is the obscuration of fundus by vitreous cells and protein exudation. Each of the 9-step scale (from grade 0 [low opacity] to 8 [more opacity]) images (in increasing order of opacity) are equivalent to approximately 0.3 log units of degradation in visual acuity based on the Bangerter calibration. Participants with prednisone dose <10 mg/day (or equivalent oral corticosteroid) were also evaluated.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent-to-treat population (mITT) included all randomized participants who received at least 1 injection analyzed according to the group to which the participant was allocated by the randomization schedule. Modified multiple imputation approach was used on VH missing adjudicated scores.
Arm/Group Title Placebo (Part A) Sarilumab 200 mg q2w (Part A)
Hide Arm/Group Description:
Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Overall Number of Participants Analyzed 20 38
Measure Type: Number
Unit of Measure: Percentage of participants
30.0 46.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Part A), Sarilumab 200 mg q2w (Part A)
Comments Analysis was performed using combined estimate for odds ratio obtained by combining the log-transformation of odds ratio from Cochran Mantel-Haenszel (CMH) analyses of the different imputed datasets, using Rubin's formulae, and then by back-transforming the combined estimate. The CMH analyses were adjusted for randomization stratification factor VH level (VH >= 4 versus VH <4).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2354
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.1
Confidence Interval (2-Sided) 90%
0.8 to 5.6
Estimation Comments Sarilumab 200 mg q2w vs Placebo
2.Secondary Outcome
Title Change From Baseline in VH Scale at Week 16
Hide Description Change from baseline in VH scale was evaluated on Miami 9-step scale. VH is the obscuration of fundus by vitreous cells and protein exudation. Each of the 9-step scale (from grade 0 [low opacity] to 8 [more opacity]) images (in increasing order of opacity) were equivalent to approximately 0.3 log units of degradation in visual acuity based on the Bangerter calibration. Least squares (LS) mean was calculated using mixed model for repeated measurements (MMRM) model with treatment groups, visits and visit-by-treatment groups interaction as fixed categorical effects as well as fixed continuous covariate of baseline adjudicated VH.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Number of participants analyzed = participants with VH assessment at baseline and post-baseline visits.
Arm/Group Title Placebo (Part A) Sarilumab 200 mg q2w (Part A)
Hide Arm/Group Description:
Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Overall Number of Participants Analyzed 13 28
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.1  (0.23) -0.9  (0.16)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Part A), Sarilumab 200 mg q2w (Part A)
Comments Analysis was performed using mixed effect model with repeated measures (MMRM) with treatment groups, visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline adjudicated VH.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0127
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Square (LS) Mean Difference
Estimated Value -0.7
Confidence Interval (2-Sided) 90%
-1.223 to -0.262
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.29
Estimation Comments Sarilumab 200 mg q2w vs Placebo
3.Secondary Outcome
Title Percentage of Participants With Anterior Chamber (AC) Cell Score = 0 or At Least 2-step Reduction in Score at Week 16
Hide Description Participants with AC cell score = 0 or with ≥2 step reduction from baseline at Week 16 were evaluated. Slit lamp examinations were conducted at each visit to assess AC cell count. The number of AC cells observed within a 1 mm × 1 mm slit beam was used to determine the grade according to the Standardization of Uveitis Nomenclature (SUN) criteria: grade 0 = no cells; grade +0.5 = 1 - 5 cells; grade +1 = 6 - 25 cells; grade +2= 26 - 50 cells; grade +3 = too many to count.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Number of participants analyzed = participants with non-missing AC cell score at Week 16.
Arm/Group Title Placebo (Part A) Sarilumab 200 mg q2w (Part A)
Hide Arm/Group Description:
Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Overall Number of Participants Analyzed 15 29
Measure Type: Number
Unit of Measure: Percentage of participants
86.7 86.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Part A), Sarilumab 200 mg q2w (Part A)
Comments Analysis was performed using common odds ratio which came from CMH analysis adjusted for randomization stratification factor VH level (VH >=4 versus VH <4).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.95
Confidence Interval (2-Sided) 90%
0.11 to 6.093
Estimation Comments Sarilumab 200 mg q2w vs Placebo
4.Secondary Outcome
Title Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at Week 16
Hide Description BCVA score is based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters, and then at 1 meter. The range of ETDRS is 0 to 100 letters. The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. LS mean was calculated using MMRM model with treatment groups, randomization strata of VH level (<4, >=4), visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline BCVA.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Number of participants analyzed = participants with BCVA score assessment at baseline and post-baseline visits.
Arm/Group Title Placebo (Part A) Sarilumab 200 mg q2w (Part A)
Hide Arm/Group Description:
Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Overall Number of Participants Analyzed 15 29
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
3.5  (1.84) 9.3  (1.36)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Part A), Sarilumab 200 mg q2w (Part A)
Comments Analysis was performed using MMRM model with treatment groups, randomization strata of VH level (<4, >=4), visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline BCVA.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0153
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 5.8
Confidence Interval (2-Sided) 90%
1.99 to 9.67
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.26
Estimation Comments Sarilumab 200 mg q2w vs Placebo
5.Secondary Outcome
Title Change From Baseline in Central Retinal Thickness (CRT) At Week 16
Hide Description CRT was measured by spectral domain optical coherence tomography (SD-OCT), a non-invasive diagnostic system providing high-resolution imaging sections of the retina. All images were transmitted to the central reading center. SD-OCT was performed in the study eye after pupil dilation. LS mean was calculated using MMRM model with treatment groups, randomization strata of VH level (<4, >=4), visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline CRT.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Number of participants analyzed = participants with CRT assessment at baseline and post-baseline visits.
Arm/Group Title Placebo (Part A) Sarilumab 200 mg q2w (Part A)
Hide Arm/Group Description:
Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Overall Number of Participants Analyzed 14 29
Least Squares Mean (Standard Error)
Unit of Measure: µm (microns)
-8.9  (11.46) -35.4  (8.36)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Part A), Sarilumab 200 mg q2w (Part A)
Comments Analysis was performed using MMRM model with treatment groups, randomization strata of VH level (<4, >=4), visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline CRT (Automatic measurement from SD-OCT).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0683
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -26.5
Confidence Interval (2-Sided) 90%
-50.41 to -2.68
Parameter Dispersion
Type: Standard Error of the Mean
Value: 14.2
Estimation Comments Sarilumab 200 mg q2w vs Placebo
6.Secondary Outcome
Title Percent Change From Baseline in CRT at Week 16
Hide Description CRT was measured by SD-OCT, a non-invasive diagnostic system providing high-resolution imaging sections of the retina. All images were transmitted to the central reading center. SD-OCT was performed in the study eye after pupil dilation. LS mean was calculated using MMRM model with treatment groups, randomization strata of VH level (<4, >=4), visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline CRT.
Time Frame Baseline to Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Number of participants analyzed = participants with CRT assessment at baseline and post-baseline visits.
Arm/Group Title Placebo (Part A) Sarilumab 200 mg q2w (Part A)
Hide Arm/Group Description:
Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Overall Number of Participants Analyzed 14 29
Least Squares Mean (Standard Error)
Unit of Measure: percent change
0.0  (2.90) -6.4  (2.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Part A), Sarilumab 200 mg q2w (Part A)
Comments Analysis was performed using MMRM model with treatment groups, randomization strata of VH level (<4, >=4), visits and visit-by-treatment groups interaction as fixed categorical effects, as well as, fixed continuous covariate of baseline CRT (Automatic measurement from SD-OCT).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0825
Comments Threshold for significance at 0.05 level.
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -6.4
Confidence Interval (2-Sided) 90%
-12.374 to -0.35
Parameter Dispersion
Type: Standard Error of the Mean
Value: 3.55
Estimation Comments Sarilumab 200 mg q2w vs Placebo
7.Secondary Outcome
Title Percentage of Participants With CRT Thickness <300 Microns at Week 16
Hide Description [Not Specified]
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
This endpoint was replaced by the percent change from baseline in CRT at Week 16 as this is more clinically relevant. Zero participant was analyzed.
Arm/Group Title Placebo (Part A) Sarilumab 200 mg q2w (Part A)
Hide Arm/Group Description:
Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Percentage of Participants Without Retinal Vessel Leakage on Fluorescein Angiography (FA) at Week 16
Hide Description [Not Specified]
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis of this endpoint was not performed as no retinal vessel leakage data was collected at Week 16. Zero participants were analyzed.
Arm/Group Title Placebo (Part A) Sarilumab 200 mg q2w (Part A)
Hide Arm/Group Description:
Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
9.Secondary Outcome
Title Percentage of Participants With Prednisone Dose of ≤5 mg/Day (or Equivalent Oral Corticosteroid) at Week 16
Hide Description Participants with prednisone dose ≤5 mg/day (or equivalent oral corticosteroid) at Week 16 were evaluated.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on mITT population. Number of participants analyzed = participants with non-missing data for prednisone (or equivalent oral corticosteroid) dose at Week 16.
Arm/Group Title Placebo (Part A) Sarilumab 200 mg q2w (Part A)
Hide Arm/Group Description:
Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
Overall Number of Participants Analyzed 15 29
Measure Type: Number
Unit of Measure: Percentage of participants
40.0 41.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo (Part A), Sarilumab 200 mg q2w (Part A)
Comments Analysis was performed using common odds ratio which came from CMH analysis adjusted for randomization stratification factor VH level (VH >=4 versus VH <4).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1
Comments Threshold for significance at 0.05 level.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.07
Confidence Interval (2-Sided) 90%
0.306 to 3.845
Estimation Comments Sarilumab 200 mg q2w vs Placebo
10.Secondary Outcome
Title Pharmacokinetics (PK) Assessment: Serum Functional Sarilumab Concentration
Hide Description Serum functional (unbound) sarilumab concentrations were determined using an enzyme-linked immunosorbent assay (ELISA) method with a lower limit of quantification (LLOQ) of 294 ng/mL. Concentrations below LLOQ were set to zero for samples at predose. Post-treatment concentrations below LLOQ were replaced by LLOQ/2. The samples were considered non-eligible for the analysis if the previous dosing time was <11 days or >17 days before the sampling time for every other week regimens.
Time Frame Predose on Day 1 (Baseline), Week 2, 4, 8, 12, 16, 24, 36, 52, and end of study (EOS) (Week 56)
Hide Outcome Measure Data
Hide Analysis Population Description
PK population: all participants who received at least one dose or part of a dose of investigational medicinal product (IMP) with at least one post-dose, non-missing serum concentration value and were analyzed according to treatment actually received. Data of this endpoint was planned to be analyzed for Sarilumab 200 mg q2w arm in Part A and B only.
Arm/Group Title Sarilumab 200 mg q2w (Part A + Part B)
Hide Arm/Group Description:
Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B).
Overall Number of Participants Analyzed 38
Mean (Standard Deviation)
Unit of Measure: ng/mL
At Baseline Number Analyzed 37 participants
0.0  (0.0)
At Week 2 Number Analyzed 29 participants
7383.3  (6547.1)
At Week 4 Number Analyzed 32 participants
9876.6  (8262.9)
At Week 8 Number Analyzed 31 participants
15958.9  (12813.1)
At Week 12 Number Analyzed 26 participants
19705.2  (15480.9)
At Week 16 Number Analyzed 26 participants
19598.4  (17280.8)
At Week 24 Number Analyzed 19 participants
22406.8  (14584.2)
At Week 36 Number Analyzed 14 participants
24375.4  (19121.7)
At Week 52 Number Analyzed 5 participants
25046.0  (17870.7)
EOS (Week 56) Number Analyzed 1 participants
1730.0 [1]   (NA)
[1]
As only one participant was analyzed at EOS, standard deviation could not be calculated.
Time Frame All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (6 weeks after the last treatment administration [Week 56]) regardless of seriousness or relationship to investigational product.
Adverse Event Reporting Description Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on treatment period' (time from the first injection of IMP to the last injection of IMP + 6 weeks).
 
Arm/Group Title Placebo (Part A + Part B) Sarilumab 200 mg q2w (Part A+ Part B) Sarilumab 200 mg q2w: Open-Label Treatment (Part C)
Hide Arm/Group Description Placebo (for Sarilumab) SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B). Sarilumab 200 mg SC injection q2w for 16 weeks during principal treatment period (Part A) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice. Responders continued with the same treatment regimen up to Week 50 during extension treatment period (Part B). Non-responders and non-completers observed in Part A were proposed to be treated with Sarilumab 200 mg SC injection q2w for 34 weeks as open-label treatment in open-label treatment period (Part-C) with background therapy of Prednisone (or equivalent oral corticosteroid) ≥15 mg/day and <80 mg/day as single therapy or in combination with MTX 10 to 25 mg/week and folic acid per local prescribing practice.
All-Cause Mortality
Placebo (Part A + Part B) Sarilumab 200 mg q2w (Part A+ Part B) Sarilumab 200 mg q2w: Open-Label Treatment (Part C)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Placebo (Part A + Part B) Sarilumab 200 mg q2w (Part A+ Part B) Sarilumab 200 mg q2w: Open-Label Treatment (Part C)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/20 (10.00%)   5/38 (13.16%)   0/21 (0.00%) 
Blood and lymphatic system disorders       
Neutropenia  1  0/20 (0.00%)  1/38 (2.63%)  0/21 (0.00%) 
Eye disorders       
Uveitis  1  0/20 (0.00%)  1/38 (2.63%)  0/21 (0.00%) 
Infections and infestations       
Staphylococcal sepsis  1  1/20 (5.00%)  0/38 (0.00%)  0/21 (0.00%) 
Investigations       
Intraocular pressure increased  1  1/20 (5.00%)  0/38 (0.00%)  0/21 (0.00%) 
Liver function test increased  1  0/20 (0.00%)  1/38 (2.63%)  0/21 (0.00%) 
Nervous system disorders       
Hypoaesthesia  1  1/20 (5.00%)  0/38 (0.00%)  0/21 (0.00%) 
Surgical and medical procedures       
Abortion induced  1  0/20 (0.00%)  2/38 (5.26%)  0/21 (0.00%) 
Vascular disorders       
Deep vein thrombosis  1  1/20 (5.00%)  0/38 (0.00%)  0/21 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra 19.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo (Part A + Part B) Sarilumab 200 mg q2w (Part A+ Part B) Sarilumab 200 mg q2w: Open-Label Treatment (Part C)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/20 (65.00%)   25/38 (65.79%)   15/21 (71.43%) 
Blood and lymphatic system disorders       
Neutropenia  1  0/20 (0.00%)  4/38 (10.53%)  1/21 (4.76%) 
Eye disorders       
Cataract  1  1/20 (5.00%)  2/38 (5.26%)  0/21 (0.00%) 
Retinal infiltrates  1  1/20 (5.00%)  2/38 (5.26%)  0/21 (0.00%) 
Uveitis  1  2/20 (10.00%)  6/38 (15.79%)  1/21 (4.76%) 
Visual impairment  1  1/20 (5.00%)  0/38 (0.00%)  2/21 (9.52%) 
Gastrointestinal disorders       
Aphthous ulcer  1  0/20 (0.00%)  2/38 (5.26%)  2/21 (9.52%) 
Diarrhoea  1  0/20 (0.00%)  1/38 (2.63%)  3/21 (14.29%) 
Nausea  1  1/20 (5.00%)  3/38 (7.89%)  1/21 (4.76%) 
General disorders       
Fatigue  1  0/20 (0.00%)  3/38 (7.89%)  0/21 (0.00%) 
Injection site bruising  1  0/20 (0.00%)  2/38 (5.26%)  0/21 (0.00%) 
Injection site swelling  1  0/20 (0.00%)  2/38 (5.26%)  0/21 (0.00%) 
Pyrexia  1  2/20 (10.00%)  0/38 (0.00%)  0/21 (0.00%) 
Hepatobiliary disorders       
Hepatic steatosis  1  0/20 (0.00%)  2/38 (5.26%)  0/21 (0.00%) 
Infections and infestations       
Bronchitis  1  2/20 (10.00%)  1/38 (2.63%)  0/21 (0.00%) 
Ear infection  1  0/20 (0.00%)  2/38 (5.26%)  0/21 (0.00%) 
Influenza  1  0/20 (0.00%)  4/38 (10.53%)  2/21 (9.52%) 
Nasopharyngitis  1  1/20 (5.00%)  2/38 (5.26%)  6/21 (28.57%) 
Upper respiratory tract infection  1  1/20 (5.00%)  2/38 (5.26%)  1/21 (4.76%) 
Urinary tract infection  1  0/20 (0.00%)  2/38 (5.26%)  2/21 (9.52%) 
Injury, poisoning and procedural complications       
Accidental overdose  1  4/20 (20.00%)  3/38 (7.89%)  1/21 (4.76%) 
Contusion  1  0/20 (0.00%)  2/38 (5.26%)  1/21 (4.76%) 
Investigations       
Alanine aminotransferase increased  1  0/20 (0.00%)  2/38 (5.26%)  0/21 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/20 (0.00%)  2/38 (5.26%)  0/21 (0.00%) 
Nervous system disorders       
Dizziness  1  0/20 (0.00%)  3/38 (7.89%)  0/21 (0.00%) 
Headache  1  2/20 (10.00%)  4/38 (10.53%)  2/21 (9.52%) 
Hypoaesthesia  1  1/20 (5.00%)  2/38 (5.26%)  0/21 (0.00%) 
Pregnancy, puerperium and perinatal conditions       
Pregnancy  1  0/20 (0.00%)  2/38 (5.26%)  0/21 (0.00%) 
Psychiatric disorders       
Middle insomnia  1  0/20 (0.00%)  2/38 (5.26%)  0/21 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  3/20 (15.00%)  4/38 (10.53%)  0/21 (0.00%) 
Skin and subcutaneous tissue disorders       
Hyperhidrosis  1  0/20 (0.00%)  2/38 (5.26%)  0/21 (0.00%) 
Vascular disorders       
Behcet's syndrome  1  1/20 (5.00%)  1/38 (2.63%)  3/21 (14.29%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDra 19.0
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
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: Sanofi
EMail: Contact-US@sanofi.com
Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01900431    
Other Study ID Numbers: ACT13480
2012-004845-34
U1111-1130-6500 ( Other Identifier: UTN )
First Submitted: July 11, 2013
First Posted: July 16, 2013
Results First Submitted: May 23, 2017
Results First Posted: June 20, 2017
Last Update Posted: June 20, 2017