Primary Objective: -To demonstrate that sarilumab added to methotrexate (MTX) reduce signs and symptoms of rheumatoid arthritis (RA) in Japanese RA participants with an inadequate response to MTX. Secondary Objective: -To assess the safety of sarilumab added to MTX in Japanese RA participants with an inadequate response to MTX.
The total duration of study was expected up to 62 weeks (screening period of 4 weeks, treatment period of 52 weeks, and a 6-week post treatment observation).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
243
Pharmaceutical form: solution for injection Route of administration: subcutaneous
Pharmaceutical form: solution for injection Route of administration: subcutaneous
Dispensed according to local practice.
Percentage of Participants Achieving American College of Rheumatology 20 (ACR20) Response at Week 24
American College of Rheumatology (ACR) response is a composite rating scale that includes 7 variables: tender joints count (TJC \[68 joints\]); Swollen joints count (SJC \[66 joints\]); levels of an acute phase reactant (high sensitivity C-reactive protein \[hs-CRP level\]); participant's assessment of pain (measured on 0 \[no pain\]-100 mm \[worst pain\] visual analog scale \[VAS\]); participant's global assessment of disease activity (measured on 0 \[no arthritis activity\]-100 mm \[maximal arthritis activity\] VAS); physician's global assessment of disease activity (measured on 0 \[no arthritis activity\]-100 mm \[maximal arthritis activity\] VAS); participant's assessment of physical function (measured by health assessment questionnaire disability index \[HAQ-DI\], with scoring range of 0 \[better health\] - 3 \[worst health\]). ACR20 response was defined as achieving at least 20% improvement in both TJC and SJC, and at least 20% improvement in at least 3 of the 5 other assessments.
Time frame: Week 24
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after informed consent form is signed. AE includes serious as well as non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, In-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Any AEs that developed or worsened or became serious during double-blind on-treatment period, single-blind on-treatment period up to 6-week post-treatment follow-up period (up to Week 58) were considered treatment-emergent.
Time frame: For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
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Dispensed according to local practice.
Investigational Site Number 392010
Asahi-Shi, Japan
Investigational Site Number 392001
Asahikawa-Shi, Japan
Investigational Site Number 392035
Asahikawa-Shi, Japan
Investigational Site Number 392070
Beppu-Shi, Japan
Investigational Site Number 392036
Chiba, Japan
Investigational Site Number 392083
Chūōku, Japan
Investigational Site Number 392047
Fuchu-Shi, Japan
Investigational Site Number 392004
Fukui-shi, Japan
Investigational Site Number 392007
Fukuoka, Japan
Investigational Site Number 392038
Fukuoka, Japan
...and 86 more locations
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities
Criteria for potentially clinically significant vital sign abnormalities: * Systolic blood pressure supine (SBP\[S\]): \<=95 mmHg and decrease from baseline (DFB) \>=20 mmHg; \>=160 mmHg and increase from baseline (IFB) \>=20 mmHg * Diastolic blood pressure supine (DBP\[S\]): \<=45 mmHg and DFB \>=10 mmHg; \>=110 mmHg and IFB \>=10 mmHg * Orthostatic systolic blood pressure (SBP\[O\]): \<=-20 mmHg * Orthostatic diastolic blood pressure (DBP\[O\]): \<=-10 mmHg * Heart rate supine (HR\[S\]): \<=50 beats per minute (bpm) and DFB \>=20 bpm; \>=120 bpm and IFB \>=20 bpm * Weight: \>=5% DFB; \>=5% IFB
Time frame: For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities
Criteria for potentially clinically significant ECG abnormalities: * PR Interval: \>200 millisecond (ms); \>200 ms and IFB \>=25%; \>220 ms; \>220 ms and IFB \>=25%; \>240 ms; \>240 ms and IFB \>=25% * QRS Interval: \>110 ms; \>110 ms and IFB \>=25%; \>120 ms; \>120 ms and IFB \>=25% * QT Interval: \>500 ms * QTc Bazett (QTc B): \>450 ms; 480 ms; 500 ms; IFB \>30 and \<=60 ms; IFB \>60 ms * QTc Fridericia (QTc F): \>450 ms; 480 ms; 500 ms; IFB \>30 and \<=60 ms; IFB \>60 ms
Time frame: For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters
Criteria for potentially clinically significant abnormalities: * Hemoglobin: \<=115 g/L (Male\[M\]) or \<=95 g/L (Female\[F\]); \>=185 g/L (M) or \>=165 g/L (F); DFB \>=20 g/L * Hematocrit: \<=0.37 v/v (M) or \<=0.32 v/v (F); \>=0.55 v/v (M) or \>=0.5 v/v (F) * Red blood cells (RBC): \>=6 Tera/L * Platelets: \<50 Giga/L; \>=50 and \<100 Giga/L; \>=700 Giga/L * White blood cells (WBC): \<3.0 Giga/L (Non-Black\[NB\]) or \<2.0 Giga/L (Black\[B\]); \>=16.0 Giga/L * Neutrophils: \<1.5 Giga/L (NB) or \<1.0 Giga/L (B); \<1.0 Giga/L * Lymphocytes: \<0.5 Giga/L; \>=0.5 Giga/L and \< lower limit of normal (LLN); \>4.0 Giga/L * Monocytes: \>0.7 Giga/L * Basophils: \>0.1 Giga/L * Eosinophils: \>0.5 Giga/L or \>upper limit of normal (ULN) (if ULN \>=0.5 Giga/L)
Time frame: For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters
Criteria for potentially clinically significant abnormalities: * Glucose: \<=3.9 mmol/L and \<LLN; \>=11.1 mmol/L unfasted or \>=7 mmol/L fasted * Hemoglobin A1c (HbA1c): \>8% * Total cholesterol: \>=6.2 mmol/L; \>=7.74 mmol/L * LDL cholesterol: \>=4.1 mmol/L; \>=4.9 mmol/L * Triglycerides: \>=4.6 mmol/L; \>=5.6 mmol/L
Time frame: For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes
Criteria for potentially clinically significant abnormalities: * Sodium: \<=129 mmol/L; \>=160 mmol/L * Potassium: \<3 mmol/L; \>=5.5 mmol/L * Chloride: \<80 mmol/L; \>115 mmol/L
Time frame: For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters
Criteria for potentially clinically significant abnormalities: * Creatinine: \>=150 micromol/L; \>=30% change from baseline; \>=100% change from baseline * Creatinine clearance: \<15 mL/min; \>=15 to \<30 mL/min; \>=30 to \< 60 mL/min; \>=60 to \<90 mL/min * Blood urea nitrogen: \>=17 mmol/L * Uric acid: \<120 micromol/L; \>408 micromol/L
Time frame: For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm: Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58
Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters
Criteria for potentially clinically significant abnormalities: * Alanine Aminotransferase (ALT): \>1 ULN and \<=1.5 ULN; \>1.5 ULN and \<=3 ULN; \>3 ULN and \<=5 ULN; \>5 ULN and \<=10 ULN; \>10 ULN and \<=20 ULN; \>20 ULN * Aspartate aminotransferase (AST): \>1 ULN and \<=1.5 ULN; \>1.5 ULN and \<=3 ULN; \>3 ULN and \<=5 ULN; \>5 ULN and \<=10 ULN; \>10 ULN and \<=20 ULN; \>20 ULN * Alkaline phosphatase: \>1.5 ULN * Total bilirubin (TBILI): \>1.5 ULN; \>2 ULN * Conjugated bilirubin (CBILI): \>1.5 ULN; \>2 ULN * Unconjugated bilirubin: \>1.5 ULN; \>2 ULN * ALT and TBILI: ALT \>3 ULN and TBILI \>2 ULN * CBILI and TBILI: CBILI \>35% TBILI and TBILI \>1.5 ULN * Albumin: \<=25 g/L
Time frame: For placebo arm: Baseline up to Week 24; For sarilumab 150 mg/150 mg, sarilumab 200 mg/200 mg and sarilumab rescue arm : Baseline up to Week 58; For placebo/sarilumab 150 mg and placebo/sarilumab 200 mg arm: Week 25 up to Week 58