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)

Rheumatoid Arthritis Clinical Trial

Official title:

A Randomized, Double-blind, Multicenter Study Evaluating the Safety and Efficacy of Sarilumab Added to Non-MTX DMARDs or as Monotherapy in Japanese Patients With Active Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02373202
• Other study ID #: LTS13618
• Secondary ID: U1111-1160-6525
• Status: Completed
• Phase: Phase 3
• First received: February 12, 2015
• Last updated: January 5, 2018
• Start date: February 2015
• Est. completion date: November 2016

Study information

• Verified date: January 2018
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion criteria:

Diagnosis of rheumatoid arthritis (RA), according to the American College of Rheumatology/The European League Against Rheumatism (ACR/EULAR) 2010 Rheumatoid Arthritis Classification Criteria with >=3 months disease duration.

Moderately to severely active RA defined as:

• At least 4 of 68 tender joints and 4 of 66 swollen joints at screening visit.

• High sensitivity C-Reactive Protein (hs-CRP) >=4 mg/L or Erythrocyte Sedimentation Rate (ESR) >=28 mm/hr at screening visit.

For the combination stratum:

Participants who had continuous treatment with non-biologic DMARDs other than MTX for at least 12 weeks prior to the randomization and on a stable dose for a minimum of 6 weeks prior to screening.

For the monotherapy stratum:

Participants who per investigator judgment were any of inappropriate, intolerant or inadequate to MTX treatment.

Exclusion criteria:

Participants <20 years of age. Prior treatment with tumor necrosis factor (TNF) antagonists or any other RA-directed biologic agents without the appropriate off-drug period prior to screening.

Prior treatment with anti-interleukin-6 (anti-IL-6) or anti-interleukin-6 receptor (IL-6R) antagonist therapies, including but not limited to tocilizumab or sarilumab.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Sarilumab
Pharmaceutical form:solution
• Sulfasalazine
Pharmaceutical form: Tablet Route of administration: Oral
• Leflunomide
Pharmaceutical form: Tablet Route of administration: Oral
• Bucillamine
Pharmaceutical form: Tablet Route of administration: Oral
• Tacrolimus
Pharmaceutical form: Capsule Route of administration: Oral
• Mizoribine
Pharmaceutical form: Tablet Route of administration: Oral

Locations

Country	Name	City	State
Japan	Investigational Site Number 392010	Asahi-Shi
Japan	Investigational Site Number 392001	Asahikawa-Shi
Japan	Investigational Site Number 392070	Beppu-Shi
Japan	Investigational Site Number 392036	Chiba-Shi
Japan	Investigational Site Number 392083	Chuo-Ku
Japan	Investigational Site Number 392004	Fukui-Shi
Japan	Investigational Site Number 392039	Fukuoka-Shi
Japan	Investigational Site Number 392030	Ichinomiya-Shi
Japan	Investigational Site Number 392002	Iizuka-Shi
Japan	Investigational Site Number 392019	Kagoshima-Shi
Japan	Investigational Site Number 392066	Kamakura-Shi
Japan	Investigational Site Number 392050	Kato-Shi
Japan	Investigational Site Number 392037	Kawachi-Nagano-Shi
Japan	Investigational Site Number 392099	Kawasaki-Shi
Japan	Investigational Site Number 392013	Kitakyushu-Shi
Japan	Investigational Site Number 392097	Kochi-Shi
Japan	Investigational Site Number 392065	Kushiro-Shi
Japan	Investigational Site Number 392026	Matsuyama-Shi
Japan	Investigational Site Number 392034	Miyagi-Gun
Japan	Investigational Site Number 392076	Nagoya-Shi
Japan	Investigational Site Number 392080	Nagoya-Shi
Japan	Investigational Site Number 392046	Narashino-Shi
Japan	Investigational Site Number 392059	Oita-Shi
Japan	Investigational Site Number 392062	Okayama-Shi
Japan	Investigational Site Number 392027	Osaki-Shi
Japan	Investigational Site Number 392049	Sagamihara-Shi
Japan	Investigational Site Number 392014	Sapporo-Shi
Japan	Investigational Site Number 392041	Sapporo-Shi
Japan	Investigational Site Number 392073	Sapporo-Shi
Japan	Investigational Site Number 392006	Sasebo-Shi
Japan	Investigational Site Number 392021	Sendai-Shi
Japan	Investigational Site Number 392022	Sendai-Shi
Japan	Investigational Site Number 392033	Sendai-Shi
Japan	Investigational Site Number 392071	Sendai-Shi
Japan	Investigational Site Number 392029	Shizuoka-Shi
Japan	Investigational Site Number 392023	Takaoka-Shi
Japan	Investigational Site Number 392003	Tomakomai-Shi
Japan	Investigational Site Number 392074	Urasoe-Shi
Japan	Investigational Site Number 392079	Urayasu-Shi
Japan	Investigational Site Number 392048	Yokohama-Shi

Sponsors (2)

Lead Sponsor	Collaborator
Sanofi	Regeneron Pharmaceuticals

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	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.	Baseline up to Week 58
Primary	Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities	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% IFB	Baseline up to Week 58
Primary	Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities	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 ms	Baseline up to Week 58
Primary	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 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)	Baseline up to Week 58
Primary	Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters	Criteria for potentially clinically significant abnormalities: Glucose: <=3.9 mmol/L and 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	Baseline up to Week 58
Primary	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	Baseline up to Week 58
Primary	Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters	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/L	Baseline up to Week 58
Primary	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; Unconjugated bilirubin: >1.5 ULN; ALT >3 ULN and TBILI >2 ULN; CBILI >35% TBILI and TBILI >1.5 ULN; Albumin: <=25 g/L	Baseline up to Week 58
Secondary	Percentage of Participants Achieving American College of Rheumatology (ACR) 20, 50 and 70 Responses at 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.	Week 52
Secondary	Change From Baseline at Week 52 in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP)	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.	Baseline, Week 52
Secondary	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at 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.	Baseline, Week 52