A Study Assessing the Efficacy and Safety of Sarilumab Added to MTX in Japanese Patients With Moderately to Severely Active Rheumatoid Arthritis (SARIL-RA-KAKEHASI)

Rheumatoid Arthritis Clinical Trial

Official title:

A Randomized, Double-blind, Multicenter Study With a Placebo-controlled Period Assessing the Efficacy and Safety of Sarilumab Added to Methotrexate (MTX) in Japanese Patients With Moderately to Severely Active Rheumatoid Arthritis Who Are Inadequate Responders to MTX Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02293902
• Other study ID #: EFC14059
• Secondary ID: U1111-1155-7401
• Status: Completed
• Phase: Phase 3
• First received: November 13, 2014
• Last updated: January 5, 2018
• Start date: November 2014
• Est. completion date: October 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 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.

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 243
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 75 Years

Eligibility

Inclusion criteria:

• Diagnosis of 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 8 of 68 tender joints and 6 of 66 swollen joints at screening visit.

• High sensitivity C-Reactive Protein (hs-CRP) >=6mg/L at screening visit.

Exclusion criteria:

• Participants <20 or >75 years of age.

• Treatment with any Disease-modifying antirheumatic drug (DMARD) other than MTX or biologic agent 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 SAR153191 (REGN88)
Pharmaceutical form: solution for injection Route of administration: subcutaneous

Other:
• Placebo (for sarilumab)
Pharmaceutical form: solution for injection Route of administration: subcutaneous

Drug:
• Methotrexate
Dispensed according to local practice.
• Folic acid
Dispensed according to local practice.

Locations

Country	Name	City	State
Japan	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-Shi
Japan	Investigational Site Number 392083	Chuo-Ku
Japan	Investigational Site Number 392047	Fuchu-Shi
Japan	Investigational Site Number 392004	Fukui-Shi
Japan	Investigational Site Number 392007	Fukuoka-Shi
Japan	Investigational Site Number 392038	Fukuoka-Shi
Japan	Investigational Site Number 392039	Fukuoka-Shi
Japan	Investigational Site Number 392078	Fukushima-Shi
Japan	Investigational Site Number 392054	Funabashi-Shi
Japan	Investigational Site Number 392015	Hachioji-Shi
Japan	Investigational Site Number 392085	Hannan-Shi
Japan	Investigational Site Number 392091	Hiroshima-Shi
Japan	Investigational Site Number 392098	Hiroshima-Shi
Japan	Investigational Site Number 392009	Hitachinaka-Shi
Japan	Investigational Site Number 392011	Hitachinaka-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 392086	Kamogawa-Shi
Japan	Investigational Site Number 392050	Kato-Shi
Japan	Investigational Site Number 392037	Kawachi-Nagano-Shi
Japan	Investigational Site Number 392093	Kawagoe-Shi
Japan	Investigational Site Number 392099	Kawasaki-Shi
Japan	Investigational Site Number 392016	Kirishima-Shi
Japan	Investigational Site Number 392013	Kitakyushu-Shi
Japan	Investigational Site Number 392024	Kitakyushu-Shi
Japan	Investigational Site Number 392045	Kitakyushu-Shi
Japan	Investigational Site Number 392063	Kiyose-Shi
Japan	Investigational Site Number 392051	Kobe-Shi
Japan	Investigational Site Number 392097	Kochi-Shi
Japan	Investigational Site Number 392040	Koushi-Shi
Japan	Investigational Site Number 392069	Kumamoto-Shi
Japan	Investigational Site Number 392089	Kurashiki-Shi
Japan	Investigational Site Number 392065	Kushiro-Shi
Japan	Investigational Site Number 392026	Matsuyama-Shi
Japan	Investigational Site Number 392081	Matsuyama-Shi
Japan	Investigational Site Number 392094	Matsuyama-Shi
Japan	Investigational Site Number 392042	Meguro-Ku
Japan	Investigational Site Number 392082	Meguro-Ku
Japan	Investigational Site Number 392012	Mito-Shi
Japan	Investigational Site Number 392034	Miyagi-Gun
Japan	Investigational Site Number 392053	Morioka-Shi
Japan	Investigational Site Number 392032	Nagano-Shi
Japan	Investigational Site Number 392064	Nagasaki-Shi
Japan	Investigational Site Number 392043	Nagoya-Shi
Japan	Investigational Site Number 392056	Nagoya-Shi
Japan	Investigational Site Number 392076	Nagoya-Shi
Japan	Investigational Site Number 392080	Nagoya-Shi
Japan	Investigational Site Number 392031	Nakano-Ku
Japan	Investigational Site Number 392046	Narashino-Shi
Japan	Investigational Site Number 392067	Narashino-Shi
Japan	Investigational Site Number 392044	Nishinomiya-Shi
Japan	Investigational Site Number 392059	Oita-Shi
Japan	Investigational Site Number 392062	Okayama-Shi
Japan	Investigational Site Number 392008	Omura-Shi
Japan	Investigational Site Number 392057	Osaka-Shi
Japan	Investigational Site Number 392060	Osaka-Shi
Japan	Investigational Site Number 392061	Osaka-Shi
Japan	Investigational Site Number 392096	Osaka-Shi
Japan	Investigational Site Number 392027	Osaki-Shi
Japan	Investigational Site Number 392049	Sagamihara-Shi
Japan	Investigational Site Number 392072	Saitama-Shi
Japan	Investigational Site Number 392075	Sakai-Shi
Japan	Investigational Site Number 392014	Sapporo-Shi
Japan	Investigational Site Number 392068	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 392100	Sendai-Shi
Japan	Investigational Site Number 392029	Shizuoka-Shi
Japan	Investigational Site Number 392025	Sumida-Ku
Japan	Investigational Site Number 392092	Sumida-Ku
Japan	Investigational Site Number 392023	Takaoka-Shi
Japan	Investigational Site Number 392095	Takarazuka-Shi
Japan	Investigational Site Number 392020	Takasaki-Shi
Japan	Investigational Site Number 392088	Takatsuki-Shi
Japan	Investigational Site Number 392018	Tokorozawa-Shi
Japan	Investigational Site Number 392003	Tomakomai-Shi
Japan	Investigational Site Number 392005	Tomakomai-Shi
Japan	Investigational Site Number 392077	Tonami-Shi
Japan	Investigational Site Number 392052	Toshima-Ku
Japan	Investigational Site Number 392058	Toyama-Shi
Japan	Investigational Site Number 392055	Toyonaka-Shi
Japan	Investigational Site Number 392074	Urasoe-Shi
Japan	Investigational Site Number 392079	Urayasu-Shi
Japan	Investigational Site Number 392048	Yokohama-Shi
Japan	Investigational Site Number 392090	Yokohama-Shi
Japan	Investigational Site Number 392101	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	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.	Week 24
Secondary	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.	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
Secondary	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	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
Secondary	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	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
Secondary	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)	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
Secondary	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	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
Secondary	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	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
Secondary	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	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
Secondary	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	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