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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)

Primary Purpose

Rheumatoid Arthritis

Status

Completed

Phase

Phase 3

Locations

Japan

Study Type

Interventional

Intervention

Sarilumab

Sulfasalazine

Leflunomide

Bucillamine

Tacrolimus

Mizoribine

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Sarilumab 150 mg q2w + DMARDs

Sarilumab 200 mg q2w + DMARDs

Sarilumab 150 mg q2w

Sarilumab 200 mg q2w

Arm Description

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.

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.

Participants received sarilumab 150 mg, SC injection, q2w for up to 52 weeks.

Participants received sarilumab 200 mg, SC injection, q2w for up to 52 weeks.

Outcomes

Primary Outcome Measures

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.

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

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

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)

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 [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/L

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

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

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

Secondary Outcome Measures

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.

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.

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.

Full Information

NCT ID

NCT02373202

First Posted

February 12, 2015

Last Updated

January 5, 2018

Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02373202

Brief Title

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)

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2018

Overall Recruitment Status

Completed

Study Start Date

February 2015 (undefined)

Primary Completion Date

November 2016 (Actual)

Study Completion Date

November 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sanofi

Collaborators

Regeneron Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

91 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sarilumab 150 mg q2w + DMARDs

Arm Type

Experimental

Arm Description

Arm Title

Sarilumab 200 mg q2w + DMARDs

Arm Type

Experimental

Arm Description

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.

Arm Title

Sarilumab 150 mg q2w

Arm Type

Experimental

Arm Description

Participants received sarilumab 150 mg, SC injection, q2w for up to 52 weeks.

Arm Title

Sarilumab 200 mg q2w

Arm Type

Experimental

Arm Description

Participants received sarilumab 200 mg, SC injection, q2w for up to 52 weeks.

Intervention Type

Drug

Intervention Name(s)

Sarilumab

Other Intervention Name(s)

SAR153191 (REGN88)

Intervention Description

Pharmaceutical form:solution

Intervention Type

Drug

Intervention Name(s)

Sulfasalazine

Intervention Description

Pharmaceutical form: Tablet Route of administration: Oral

Intervention Type

Drug

Intervention Name(s)

Leflunomide

Intervention Description

Pharmaceutical form: Tablet Route of administration: Oral

Intervention Type

Drug

Intervention Name(s)

Bucillamine

Intervention Description

Pharmaceutical form: Tablet Route of administration: Oral

Intervention Type

Drug

Intervention Name(s)

Tacrolimus

Intervention Description

Pharmaceutical form: Capsule Route of administration: Oral

Intervention Type

Drug

Intervention Name(s)

Mizoribine

Intervention Description

Pharmaceutical form: Tablet Route of administration: Oral

Primary Outcome Measure Information:

Title

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Description

Time Frame

Baseline up to Week 58

Title

Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities

Description

Time Frame

Baseline up to Week 58

Title

Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities

Description

Time Frame

Baseline up to Week 58

Title

Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters

Description

Time Frame

Baseline up to Week 58

Title

Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters

Description

Time Frame

Baseline up to Week 58

Title

Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes

Description

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

Baseline up to Week 58

Title

Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters

Description

Time Frame

Baseline up to Week 58

Title

Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters

Description

Time Frame

Baseline up to Week 58

Secondary Outcome Measure Information:

Title

Percentage of Participants Achieving American College of Rheumatology (ACR) 20, 50 and 70 Responses at Week 52

Description

Time Frame

Week 52

Title

Change From Baseline at Week 52 in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP)

Description

Time Frame

Baseline, Week 52

Title

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52

Description

Time Frame

Baseline, Week 52

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Clinical Sciences & Operations

Organizational Affiliation

Sanofi

Official's Role

Study Director

Facility Information:

Facility Name

Investigational Site Number 392010

City

Asahi-Shi

Country

Japan

Facility Name

Investigational Site Number 392001

City

Asahikawa-Shi

Country

Japan

Facility Name

Investigational Site Number 392070

City

Beppu-Shi

Country

Japan

Facility Name

Investigational Site Number 392036

City

Chiba-Shi

Country

Japan

Facility Name

Investigational Site Number 392083

City

Chuo-Ku

Country

Japan

Facility Name

Investigational Site Number 392004

City

Fukui-Shi

Country

Japan

Facility Name

Investigational Site Number 392039

City

Fukuoka-Shi

Country

Japan

Facility Name

Investigational Site Number 392030

City

Ichinomiya-Shi

Country

Japan

Facility Name

Investigational Site Number 392002

City

Iizuka-Shi

Country

Japan

Facility Name

Investigational Site Number 392019

City

Kagoshima-Shi

Country

Japan

Facility Name

Investigational Site Number 392066

City

Kamakura-Shi

Country

Japan

Facility Name

Investigational Site Number 392050

City

Kato-Shi

Country

Japan

Facility Name

Investigational Site Number 392037

City

Kawachi-Nagano-Shi

Country

Japan

Facility Name

Investigational Site Number 392099

City

Kawasaki-Shi

Country

Japan

Facility Name

Investigational Site Number 392013

City

Kitakyushu-Shi

Country

Japan

Facility Name

Investigational Site Number 392097

City

Kochi-Shi

Country

Japan

Facility Name

Investigational Site Number 392065

City

Kushiro-Shi

Country

Japan

Facility Name

Investigational Site Number 392026

City

Matsuyama-Shi

Country

Japan

Facility Name

Investigational Site Number 392034

City

Miyagi-Gun

Country

Japan

Facility Name

Investigational Site Number 392076

City

Nagoya-Shi

Country

Japan

Facility Name

Investigational Site Number 392080

City

Nagoya-Shi

Country

Japan

Facility Name

Investigational Site Number 392046

City

Narashino-Shi

Country

Japan

Facility Name

Investigational Site Number 392059

City

Oita-Shi

Country

Japan

Facility Name

Investigational Site Number 392062

City

Okayama-Shi

Country

Japan

Facility Name

Investigational Site Number 392027

City

Osaki-Shi

Country

Japan

Facility Name

Investigational Site Number 392049

City

Sagamihara-Shi

Country

Japan

Facility Name

Investigational Site Number 392014

City

Sapporo-Shi

Country

Japan

Facility Name

Investigational Site Number 392041

City

Sapporo-Shi

Country

Japan

Facility Name

Investigational Site Number 392073

City

Sapporo-Shi

Country

Japan

Facility Name

Investigational Site Number 392006

City

Sasebo-Shi

Country

Japan

Facility Name

Investigational Site Number 392021

City

Sendai-Shi

Country

Japan

Facility Name

Investigational Site Number 392022

City

Sendai-Shi

Country

Japan

Facility Name

Investigational Site Number 392033

City

Sendai-Shi

Country

Japan

Facility Name

Investigational Site Number 392071

City

Sendai-Shi

Country

Japan

Facility Name

Investigational Site Number 392029

City

Shizuoka-Shi

Country

Japan

Facility Name

Investigational Site Number 392023

City

Takaoka-Shi

Country

Japan

Facility Name

Investigational Site Number 392003

City

Tomakomai-Shi

Country

Japan

Facility Name

Investigational Site Number 392074

City

Urasoe-Shi

Country

Japan

Facility Name

Investigational Site Number 392079

City

Urayasu-Shi

Country

Japan

Facility Name

Investigational Site Number 392048

City

Yokohama-Shi

Country

Japan

12. IPD Sharing Statement

Learn more about this trial

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)

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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

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial