A Study Assessing the Safety and Efficacy of Sarilumab Added to Non-MTX DMARDs or as Monotherapy in Japanese Patients With Active Rheumatoid Arthritis (SARIL-RA-HARUKA)
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT02373202
- Lead Sponsor
- Sanofi
- Brief Summary
Primary Objective:
To document the long-term safety of sarilumab added to non-methotrexate (non-MTX) disease-modifying antirheumatic drugs (DMARDs) or as monotherapy.
Secondary Objective:
To document the long term efficacy of sarilumab added to non-MTX DMARDs or as monotherapy.
- Detailed Description
Total study duration was up to 62 weeks: Up to 4-week screening period, 52-week treatment period, and 6-week post-treatment follow-up period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 91
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sarilumab 150 mg q2w + DMARDs Bucillamine Participants received sarilumab 150 mg, subcutaneous (SC) injection, once every two weeks (q2w) along with non-MTX DMARDs (sulfasalazine, leflunomide, bucillamine, tacrolimus, and/or mizoribine) for up to 52 weeks. Sarilumab 200 mg q2w + DMARDs Sarilumab Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs (sulfasalazine, leflunomide, bucillamine, tacrolimus, and/or mizoribine) for up to 52 weeks. Sarilumab 200 mg q2w Sarilumab Participants received sarilumab 200 mg, SC injection, q2w for up to 52 weeks. Sarilumab 150 mg q2w + DMARDs Leflunomide Participants received sarilumab 150 mg, subcutaneous (SC) injection, once every two weeks (q2w) along with non-MTX DMARDs (sulfasalazine, leflunomide, bucillamine, tacrolimus, and/or mizoribine) for up to 52 weeks. Sarilumab 150 mg q2w + DMARDs Sarilumab Participants received sarilumab 150 mg, subcutaneous (SC) injection, once every two weeks (q2w) along with non-MTX DMARDs (sulfasalazine, leflunomide, bucillamine, tacrolimus, and/or mizoribine) for up to 52 weeks. Sarilumab 150 mg q2w + DMARDs Sulfasalazine Participants received sarilumab 150 mg, subcutaneous (SC) injection, once every two weeks (q2w) along with non-MTX DMARDs (sulfasalazine, leflunomide, bucillamine, tacrolimus, and/or mizoribine) for up to 52 weeks. Sarilumab 150 mg q2w + DMARDs Mizoribine Participants received sarilumab 150 mg, subcutaneous (SC) injection, once every two weeks (q2w) along with non-MTX DMARDs (sulfasalazine, leflunomide, bucillamine, tacrolimus, and/or mizoribine) for up to 52 weeks. Sarilumab 150 mg q2w + DMARDs Tacrolimus Participants received sarilumab 150 mg, subcutaneous (SC) injection, once every two weeks (q2w) along with non-MTX DMARDs (sulfasalazine, leflunomide, bucillamine, tacrolimus, and/or mizoribine) for up to 52 weeks. Sarilumab 200 mg q2w + DMARDs Sulfasalazine Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs (sulfasalazine, leflunomide, bucillamine, tacrolimus, and/or mizoribine) for up to 52 weeks. Sarilumab 200 mg q2w + DMARDs Bucillamine Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs (sulfasalazine, leflunomide, bucillamine, tacrolimus, and/or mizoribine) for up to 52 weeks. Sarilumab 200 mg q2w + DMARDs Leflunomide Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs (sulfasalazine, leflunomide, bucillamine, tacrolimus, and/or mizoribine) for up to 52 weeks. Sarilumab 200 mg q2w + DMARDs Tacrolimus Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs (sulfasalazine, leflunomide, bucillamine, tacrolimus, and/or mizoribine) for up to 52 weeks. Sarilumab 200 mg q2w + DMARDs Mizoribine Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs (sulfasalazine, leflunomide, bucillamine, tacrolimus, and/or mizoribine) for up to 52 weeks. Sarilumab 150 mg q2w Sarilumab Participants received sarilumab 150 mg, SC injection, q2w for up to 52 weeks.
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Baseline up to Week 58 Adverse event (AE) was defined as any untoward medical occurrence in a participant who received IMP and did not necessary have to had a causal relationship with treatment. All AEs that occurred from the first dose of the IMP administration up to 6 weeks after last dose of treatment (up to Week 58) were considered as TEAEs. SAEs were AEs resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or a medically important event. TEAEs included both SAEs and non-SAEs.
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Baseline up to Week 58 Criteria for potentially clinically significant ECG abnormalities:
* PR Interval: \>200 milliseconds (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 msNumber of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters Baseline up to Week 58 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)Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters Baseline up to Week 58 Criteria for potentially clinically significant abnormalities:
* Glucose: \<=3.9 mmol/L and \<LLN; \>=11.1 mmol/L (unfasted \[unfas\]) or \>=7 mmol/L (fasted \[fas\])
* 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/LNumber of Participants With Potentially Clinically Significant Vital Signs Abnormalities Baseline up to Week 58 Criteria for potentially clinically significant vital sign abnormalities:
* Systolic blood pressure (SBP) supine: \<=95 mmHg and decrease from baseline (DFB) \>=20 mmHg; \>=160 mmHg and increase from baseline (IFB) \>=20 mmHg
* Diastolic blood pressure (DBP) supine: \<=45 mmHg and DFB \>=10 mmHg; \>=110 mmHg and IFB ≥10 mmHg
* SBP (Orthostatic): \<=-20 mmHg
* DBP (Orthostatic): \<=-10 mmHg
* Heart rate (HR) supine: \<=50 beats per minute (bpm) and DFB \>=20 bpm; \>=120 bpm and IFB \>=20 bpm
* Weight: \>=5% DFB; \>=5% IFBNumber of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes Baseline up to Week 58 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/LNumber of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Baseline up to Week 58 Criteria for potentially clinically significant abnormalities:
* Creatinine: \>=150 micromol/L (adults); \>=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/LNumber of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters Baseline up to Week 58 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
* Unconjugated bilirubin: \>1.5 ULN
* ALT \>3 ULN and TBILI \>2 ULN
* CBILI \>35% TBILI and TBILI \>1.5 ULN
* Albumin: \<=25 g/L
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving American College of Rheumatology (ACR) 20, 50 and 70 Responses at Week 52 Week 52 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 Question-Disability Index \[HAQ-DI\], with scoring range of 0 \[better health\] - 3 \[worst health\]). ACR20/50/70 response is defined as at least 20/50/70% improvement in both TJC and SJC, and at least 20/50/70% improvement in at least 3 of the 5 other assessments, respectively.
Change From Baseline at Week 52 in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP) Baseline, Week 52 DAS28-CRP is a composite score that contains 4 variables: TJC (based on 28 joints), SJC (based on 28 joints), participant's assessment of general health on VAS (range 0 \[very well\] to 100 mm \[extremely bad\]) and CRP (mg/L). DAS28-CRP total score ranges from 2-10 with a lower score indicating less disease activity. A DAS28-CRP above 5.1 indicates high disease activity, whereas below 3.2 indicates low disease activity and below 2.6 as disease remission.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52 Baseline, Week 52 HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each items's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty.
Trial Locations
- Locations (40)
Investigational Site Number 392039
🇯🇵Fukuoka-Shi, Japan
Investigational Site Number 392006
🇯🇵Sasebo-Shi, Japan
Investigational Site Number 392023
🇯🇵Takaoka-Shi, Japan
Investigational Site Number 392076
🇯🇵Nagoya-Shi, Japan
Investigational Site Number 392097
🇯🇵Kochi-Shi, Japan
Investigational Site Number 392030
🇯🇵Ichinomiya-Shi, Japan
Investigational Site Number 392022
🇯🇵Sendai-Shi, Japan
Investigational Site Number 392033
🇯🇵Sendai-Shi, Japan
Investigational Site Number 392029
🇯🇵Shizuoka-Shi, Japan
Investigational Site Number 392046
🇯🇵Narashino-Shi, Japan
Investigational Site Number 392059
🇯🇵Oita-Shi, Japan
Investigational Site Number 392027
🇯🇵Osaki-Shi, Japan
Investigational Site Number 392049
🇯🇵Sagamihara-Shi, Japan
Investigational Site Number 392003
🇯🇵Tomakomai-Shi, Japan
Investigational Site Number 392071
🇯🇵Sendai-Shi, Japan
Investigational Site Number 392036
🇯🇵Chiba-Shi, Japan
Investigational Site Number 392083
🇯🇵Chuo-Ku, Japan
Investigational Site Number 392050
🇯🇵Kato-Shi, Japan
Investigational Site Number 392037
🇯🇵Kawachi-Nagano-Shi, Japan
Investigational Site Number 392066
🇯🇵Kamakura-Shi, Japan
Investigational Site Number 392099
🇯🇵Kawasaki-Shi, Japan
Investigational Site Number 392026
🇯🇵Matsuyama-Shi, Japan
Investigational Site Number 392034
🇯🇵Miyagi-Gun, Japan
Investigational Site Number 392014
🇯🇵Sapporo-Shi, Japan
Investigational Site Number 392021
🇯🇵Sendai-Shi, Japan
Investigational Site Number 392010
🇯🇵Asahi-Shi, Japan
Investigational Site Number 392019
🇯🇵Kagoshima-Shi, Japan
Investigational Site Number 392070
🇯🇵Beppu-Shi, Japan
Investigational Site Number 392001
🇯🇵Asahikawa-Shi, Japan
Investigational Site Number 392002
🇯🇵Iizuka-Shi, Japan
Investigational Site Number 392004
🇯🇵Fukui-Shi, Japan
Investigational Site Number 392013
🇯🇵Kitakyushu-Shi, Japan
Investigational Site Number 392065
🇯🇵Kushiro-Shi, Japan
Investigational Site Number 392080
🇯🇵Nagoya-Shi, Japan
Investigational Site Number 392062
🇯🇵Okayama-Shi, Japan
Investigational Site Number 392073
🇯🇵Sapporo-Shi, Japan
Investigational Site Number 392041
🇯🇵Sapporo-Shi, Japan
Investigational Site Number 392079
🇯🇵Urayasu-Shi, Japan
Investigational Site Number 392074
🇯🇵Urasoe-Shi, Japan
Investigational Site Number 392048
🇯🇵Yokohama-Shi, Japan