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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02373202
Recruitment Status : Completed
First Posted : February 26, 2015
Results First Posted : January 30, 2018
Last Update Posted : January 30, 2018
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Sarilumab Drug: Sulfasalazine Drug: Leflunomide Drug: Bucillamine Drug: Tacrolimus Drug: Mizoribine Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 91 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : February 2015
Actual Primary Completion Date : November 2016
Actual Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Sarilumab

Arm Intervention/treatment
Experimental: Sarilumab 150 mg q2w + DMARDs
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.
Drug: Sarilumab
Pharmaceutical form:solution
Other Name: SAR153191 (REGN88)

Drug: Sulfasalazine
Pharmaceutical form: Tablet Route of administration: Oral

Drug: Leflunomide
Pharmaceutical form: Tablet Route of administration: Oral

Drug: Bucillamine
Pharmaceutical form: Tablet Route of administration: Oral

Drug: Tacrolimus
Pharmaceutical form: Capsule Route of administration: Oral

Drug: Mizoribine
Pharmaceutical form: Tablet Route of administration: Oral

Experimental: Sarilumab 200 mg q2w + DMARDs
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.
Drug: Sarilumab
Pharmaceutical form:solution
Other Name: SAR153191 (REGN88)

Drug: Sulfasalazine
Pharmaceutical form: Tablet Route of administration: Oral

Drug: Leflunomide
Pharmaceutical form: Tablet Route of administration: Oral

Drug: Bucillamine
Pharmaceutical form: Tablet Route of administration: Oral

Drug: Tacrolimus
Pharmaceutical form: Capsule Route of administration: Oral

Drug: Mizoribine
Pharmaceutical form: Tablet Route of administration: Oral

Experimental: Sarilumab 150 mg q2w
Participants received sarilumab 150 mg, SC injection, q2w for up to 52 weeks.
Drug: Sarilumab
Pharmaceutical form:solution
Other Name: SAR153191 (REGN88)

Experimental: Sarilumab 200 mg q2w
Participants received sarilumab 200 mg, SC injection, q2w for up to 52 weeks.
Drug: Sarilumab
Pharmaceutical form:solution
Other Name: SAR153191 (REGN88)




Primary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: 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.

  2. Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities [ Time Frame: 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% IFB

  3. Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities [ Time Frame: 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 ms

  4. Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters [ Time Frame: 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)

  5. Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters [ Time Frame: 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/L

  6. Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Electrolytes [ Time Frame: 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/L

  7. Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters [ Time Frame: 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/L

  8. Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters [ Time Frame: 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 :
  1. Percentage of Participants Achieving American College of Rheumatology (ACR) 20, 50 and 70 Responses at Week 52 [ Time Frame: 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.

  2. Change From Baseline at Week 52 in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP) [ Time Frame: 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.

  3. Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52 [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02373202


Locations
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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, Japan
Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Sciences & Operations Sanofi

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02373202     History of Changes
Other Study ID Numbers: LTS13618
U1111-1160-6525 ( Other Identifier: UTN )
First Posted: February 26, 2015    Key Record Dates
Results First Posted: January 30, 2018
Last Update Posted: January 30, 2018
Last Verified: January 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Tacrolimus
Leflunomide
Mizoribine
Sulfasalazine
Bucillamine
Antirheumatic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Gastrointestinal Agents
Antioxidants
Protective Agents