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)
Sponsor
Sanofi (Industry)
Overall Status
Completed
CT.gov ID
NCT02373202
Collaborator
Regeneron Pharmaceuticals (Industry)
91
40
4
21
2.3
0.1
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| 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.
Study Design
Study Type:
Interventional
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
:
Feb 1, 2015
Actual Primary Completion Date
:
Nov 1, 2016
Actual Study Completion Date
:
Nov 1, 2016
Arms and Interventions
| 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 Names:
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 Names:
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 Names:
|
| Experimental: Sarilumab 200 mg q2w Participants received sarilumab 200 mg, SC injection, q2w for up to 52 weeks. |
Drug: Sarilumab
Pharmaceutical form:solution
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 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% IFB
- 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 ms
- Number 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/L
- Number 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/L
- Number 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/L
- Number 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
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
20 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Investigational Site Number 392010 | Asahi-Shi | Japan | ||
| 2 | Investigational Site Number 392001 | Asahikawa-Shi | Japan | ||
| 3 | Investigational Site Number 392070 | Beppu-Shi | Japan | ||
| 4 | Investigational Site Number 392036 | Chiba-Shi | Japan | ||
| 5 | Investigational Site Number 392083 | Chuo-Ku | Japan | ||
| 6 | Investigational Site Number 392004 | Fukui-Shi | Japan | ||
| 7 | Investigational Site Number 392039 | Fukuoka-Shi | Japan | ||
| 8 | Investigational Site Number 392030 | Ichinomiya-Shi | Japan | ||
| 9 | Investigational Site Number 392002 | Iizuka-Shi | Japan | ||
| 10 | Investigational Site Number 392019 | Kagoshima-Shi | Japan | ||
| 11 | Investigational Site Number 392066 | Kamakura-Shi | Japan | ||
| 12 | Investigational Site Number 392050 | Kato-Shi | Japan | ||
| 13 | Investigational Site Number 392037 | Kawachi-Nagano-Shi | Japan | ||
| 14 | Investigational Site Number 392099 | Kawasaki-Shi | Japan | ||
| 15 | Investigational Site Number 392013 | Kitakyushu-Shi | Japan | ||
| 16 | Investigational Site Number 392097 | Kochi-Shi | Japan | ||
| 17 | Investigational Site Number 392065 | Kushiro-Shi | Japan | ||
| 18 | Investigational Site Number 392026 | Matsuyama-Shi | Japan | ||
| 19 | Investigational Site Number 392034 | Miyagi-Gun | Japan | ||
| 20 | Investigational Site Number 392076 | Nagoya-Shi | Japan | ||
| 21 | Investigational Site Number 392080 | Nagoya-Shi | Japan | ||
| 22 | Investigational Site Number 392046 | Narashino-Shi | Japan | ||
| 23 | Investigational Site Number 392059 | Oita-Shi | Japan | ||
| 24 | Investigational Site Number 392062 | Okayama-Shi | Japan | ||
| 25 | Investigational Site Number 392027 | Osaki-Shi | Japan | ||
| 26 | Investigational Site Number 392049 | Sagamihara-Shi | Japan | ||
| 27 | Investigational Site Number 392014 | Sapporo-Shi | Japan | ||
| 28 | Investigational Site Number 392041 | Sapporo-Shi | Japan | ||
| 29 | Investigational Site Number 392073 | Sapporo-Shi | Japan | ||
| 30 | Investigational Site Number 392006 | Sasebo-Shi | Japan | ||
| 31 | Investigational Site Number 392021 | Sendai-Shi | Japan | ||
| 32 | Investigational Site Number 392022 | Sendai-Shi | Japan | ||
| 33 | Investigational Site Number 392033 | Sendai-Shi | Japan | ||
| 34 | Investigational Site Number 392071 | Sendai-Shi | Japan | ||
| 35 | Investigational Site Number 392029 | Shizuoka-Shi | Japan | ||
| 36 | Investigational Site Number 392023 | Takaoka-Shi | Japan | ||
| 37 | Investigational Site Number 392003 | Tomakomai-Shi | Japan | ||
| 38 | Investigational Site Number 392074 | Urasoe-Shi | Japan | ||
| 39 | Investigational Site Number 392079 | Urayasu-Shi | Japan | ||
| 40 | Investigational Site Number 392048 | Yokohama-Shi | Japan |
Sponsors and Collaborators
- Sanofi
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Sciences & Operations, Sanofi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT02373202
Other Study ID Numbers:
- LTS13618
- U1111-1160-6525
First Posted:
Feb 26, 2015
Last Update Posted:
Jan 30, 2018
Last Verified:
Jan 1, 2018
Studies a U.S. FDA-regulated Drug Product:
Yes
Product Manufactured in and Exported from the U.S.:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This study was conducted at 40 centers in Japan. A total of 117 participants were screened between 23 February 2015 and 9 September 2015, 26 of whom were screen failures. |
|---|---|
| Pre-assignment Detail | A total of 91 participants were randomized to receive monotherapy stratum (in a ratio of 1:1 to sarilumab 150 mg, once in every two weeks [q2w] or sarilumab 200 mg, q2w) or combination stratum (background non-methotrexate disease modifying anti-rheumatic drugs [Non-MTX DMARDs] along with sarilumab 150/ 200 mg q2w in 1:1 ratio). |
| Arm/Group Title | Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w | Sarilumab 200 mg q2w |
|---|---|---|---|---|
| Arm/Group Description | Participants received sarilumab 150 mg, subcutaneous (SC) injection, q2w along with non-MTX DMARDs for up to 52 weeks. | Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs 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. |
| Period Title: Overall Study | ||||
| STARTED | 15 | 15 | 30 | 31 |
| COMPLETED | 13 | 9 | 27 | 30 |
| NOT COMPLETED | 2 | 6 | 3 | 1 |
Baseline Characteristics
| Arm/Group Title | Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w | Sarilumab 200 mg q2w | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received sarilumab 150 mg, SC injection, q2w along with non-MTX DMARDs for up to 52 weeks. | Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs 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. | Total of all reporting groups |
| Overall Participants | 15 | 15 | 30 | 31 | 91 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
56.3
(10.9)
|
63.3
(10.6)
|
54.4
(13.8)
|
52.5
(10.3)
|
55.6
(12.1)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
12
80%
|
13
86.7%
|
27
90%
|
26
83.9%
|
78
85.7%
|
| Male |
3
20%
|
2
13.3%
|
3
10%
|
5
16.1%
|
13
14.3%
|
Outcome Measures
| Title | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
|---|---|
| Description | 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. |
| Time Frame | Baseline up to Week 58 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomized participants who actually received at least one dose or a partial dose of IMP analyzed according to the treatment actually received. |
| Arm/Group Title | Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w | Sarilumab 200 mg q2w |
|---|---|---|---|---|
| Arm/Group Description | Participants received sarilumab 150 mg, SC injection, q2w along with non-MTX DMARDs for up to 52 weeks. | Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs 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. |
| Measure Participants | 15 | 15 | 30 | 31 |
| Any TEAE |
14
93.3%
|
13
86.7%
|
25
83.3%
|
28
90.3%
|
| SAE |
0
0%
|
3
20%
|
1
3.3%
|
2
6.5%
|
| Title | Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities |
|---|---|
| Description | 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 |
| Time Frame | Baseline up to Week 58 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomized participants who actually received at least one dose or a partial dose of IMP analyzed according to the treatment actually received. |
| Arm/Group Title | Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w | Sarilumab 200 mg q2w |
|---|---|---|---|---|
| Arm/Group Description | Participants received sarilumab 150 mg, SC injection, q2w along with non-MTX DMARDs for up to 52 weeks. | Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs 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. |
| Measure Participants | 15 | 15 | 30 | 31 |
| SBP (supine) <=95 mmHg and DFB >=20 mmHg |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| SBP (supine) >=160 mmHg and IFB >=20 mmHg |
1
6.7%
|
1
6.7%
|
1
3.3%
|
1
3.2%
|
| DBP (supine) <=45 mmHg and DFB >=10 mmHg |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| DBP (supine) >=110 mmHg and IFB >=10 mmHg |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| SBP (orthostatic) <=-20 mmHg |
8
53.3%
|
5
33.3%
|
5
16.7%
|
9
29%
|
| DBP (orthostatic) <=-10 mmHg |
3
20%
|
3
20%
|
5
16.7%
|
10
32.3%
|
| HR (supine) <=50 bpm and DFB >= 20 bpm |
0
0%
|
0
0%
|
1
3.3%
|
1
3.2%
|
| HR (supine) >=120 bpm and IFB >=20 bpm |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Weight >=5% DFB |
1
6.7%
|
1
6.7%
|
2
6.7%
|
0
0%
|
| Weight >=5% IFB |
3
20%
|
2
13.3%
|
12
40%
|
7
22.6%
|
| Title | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities |
|---|---|
| Description | 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 |
| Time Frame | Baseline up to Week 58 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomized participants who actually received at least one dose or a partial dose of IMP analyzed according to the treatment actually received. |
| Arm/Group Title | Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w | Sarilumab 200 mg q2w |
|---|---|---|---|---|
| Arm/Group Description | Participants received sarilumab 150 mg, SC injection, q2w along with non-MTX DMARDs for up to 52 weeks. | Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs 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. |
| Measure Participants | 15 | 15 | 30 | 31 |
| PR >200 ms |
0
0%
|
0
0%
|
0
0%
|
1
3.2%
|
| PR >200 ms and IFB >=25% |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| PR >220 ms |
0
0%
|
0
0%
|
0
0%
|
1
3.2%
|
| PR >220 ms and IFB >=25% |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| PR >240 ms |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| PR >240 ms and IFB >=25% |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QRS >110 ms |
0
0%
|
2
13.3%
|
0
0%
|
1
3.2%
|
| QRS >110 ms and IFB >=25% |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QRS >120 ms |
0
0%
|
2
13.3%
|
0
0%
|
0
0%
|
| QRS >120 ms and IFB >=25% |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QT >500 ms |
0
0%
|
0
0%
|
0
0%
|
1
3.2%
|
| QTc B >450 ms |
2
13.3%
|
1
6.7%
|
6
20%
|
10
32.3%
|
| QTc B >480 ms |
0
0%
|
1
6.7%
|
0
0%
|
1
3.2%
|
| QTc B >500 ms |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QTc B IFB >30 and <=60 ms |
0
0%
|
1
6.7%
|
2
6.7%
|
1
3.2%
|
| QTc B IFB >60 ms |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QTc F >450 ms |
2
13.3%
|
1
6.7%
|
2
6.7%
|
6
19.4%
|
| QTc F >480 ms |
0
0%
|
0
0%
|
0
0%
|
1
3.2%
|
| QTc F >500 ms |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QTc F IFB >30 and <=60 ms |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| QTc F IFB >60 ms |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Hematological Parameters |
|---|---|
| Description | 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) |
| Time Frame | Baseline up to Week 58 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomized participants who actually received at least one dose or a partial dose of IMP analyzed according to the treatment actually received. |
| Arm/Group Title | Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w | Sarilumab 200 mg q2w |
|---|---|---|---|---|
| Arm/Group Description | Participants received sarilumab 150 mg, SC injection, q2w along with non-MTX DMARDs for up to 52 weeks. | Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs 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. |
| Measure Participants | 15 | 15 | 30 | 31 |
| Hemoglobin <=115 g/L (M) or <=95 g/L (F) |
0
0%
|
1
6.7%
|
1
3.3%
|
3
9.7%
|
| Hemoglobin >=185 g/L (M) or >=165 g/L (F) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Hemoglobin DFB >=20 g/L |
0
0%
|
0
0%
|
0
0%
|
2
6.5%
|
| Hematocrit <=0.37 v/v (M) or <=0.32 v/v (F) |
0
0%
|
3
20%
|
2
6.7%
|
6
19.4%
|
| Hematocrit >0.55 v/v (M) or >=0.5 v/v (F) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| RBC >=6 Tera/L |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Platelets <50 Giga/L |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Platelets >=50 and <100 Giga/L |
1
6.7%
|
1
6.7%
|
1
3.3%
|
0
0%
|
| Platelets >=700 Giga/L |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| WBC <3.0 Giga/L (NB) or <2.0 Giga/L (B) |
6
40%
|
9
60%
|
7
23.3%
|
9
29%
|
| WBC >=16.0 Giga/L |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Neutrophils <1.5 Giga/L (NB) or <1.0 Giga/L (B) |
8
53.3%
|
11
73.3%
|
8
26.7%
|
13
41.9%
|
| Neutrophils <1.0 Giga/L |
5
33.3%
|
3
20%
|
2
6.7%
|
4
12.9%
|
| Lymphocytes <0.5 Giga/L |
0
0%
|
0
0%
|
0
0%
|
1
3.2%
|
| Lymphocytes >=0.5 Giga/L and <LLN |
3
20%
|
4
26.7%
|
3
10%
|
8
25.8%
|
| Lymphocytes >4.0 Giga/L |
0
0%
|
1
6.7%
|
0
0%
|
0
0%
|
| Monocytes >0.7 Giga/L |
1
6.7%
|
0
0%
|
3
10%
|
2
6.5%
|
| Basophils >0.1 Giga/L |
1
6.7%
|
0
0%
|
0
0%
|
5
16.1%
|
| Eosinophils >0.5 Giga/L or >ULN (ULN >=0.5 Giga/L) |
0
0%
|
0
0%
|
2
6.7%
|
2
6.5%
|
| Title | Percentage of Participants Achieving American College of Rheumatology (ACR) 20, 50 and 70 Responses at Week 52 |
|---|---|
| Description | 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. |
| Time Frame | Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population included all randomized participants who received at least one dose of IMP, irrespective of compliance with the study protocol and procedures. |
| Arm/Group Title | Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w | Sarilumab 200 mg q2w |
|---|---|---|---|---|
| Arm/Group Description | Participants received sarilumab 150 mg, SC injection, q2w along with non-MTX DMARDs for up to 52 weeks. | Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs 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. |
| Measure Participants | 15 | 15 | 30 | 31 |
| ACR20 |
73.3
488.7%
|
40.0
266.7%
|
76.7
255.7%
|
74.2
239.4%
|
| ACR50 |
60.0
400%
|
33.3
222%
|
56.7
189%
|
54.8
176.8%
|
| ACR70 |
53.3
355.3%
|
26.7
178%
|
26.7
89%
|
25.8
83.2%
|
| Title | Change From Baseline at Week 52 in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP) |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population included all randomized participants who received at least one dose of IMP, irrespective of compliance with the study protocol and procedures. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w | Sarilumab 200 mg q2w |
|---|---|---|---|---|
| Arm/Group Description | Participants received sarilumab 150 mg, SC injection, q2w along with non-MTX DMARDs for up to 52 weeks. | Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs 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. |
| Measure Participants | 14 | 10 | 28 | 30 |
| Mean (Standard Deviation) [units on a scale] |
-2.90
(1.06)
|
-2.47
(0.84)
|
-2.62
(1.12)
|
-2.64
(1.35)
|
| Title | Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 52 |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Week 52 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population included all randomized participants who received at least one dose of IMP, irrespective of compliance with the study protocol and procedures. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure. |
| Arm/Group Title | Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w | Sarilumab 200 mg q2w |
|---|---|---|---|---|
| Arm/Group Description | Participants received sarilumab 150 mg, SC injection, q2w along with non-MTX DMARDs for up to 52 weeks. | Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs 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. |
| Measure Participants | 14 | 10 | 28 | 30 |
| Mean (Standard Deviation) [units on a scale] |
-0.52
(0.45)
|
-0.34
(0.60)
|
-0.48
(0.58)
|
-0.38
(0.34)
|
| Title | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Metabolic Parameters |
|---|---|
| Description | 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 |
| Time Frame | Baseline up to Week 58 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomized participants who actually received at least one dose or a partial dose of IMP analyzed according to the treatment actually received. |
| Arm/Group Title | Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w | Sarilumab 200 mg q2w |
|---|---|---|---|---|
| Arm/Group Description | Participants received sarilumab 150 mg, SC injection, q2w along with non-MTX DMARDs for up to 52 weeks. | Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs 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. |
| Measure Participants | 15 | 15 | 30 | 31 |
| Glucose <=3.9 mmol/L and <LLN |
0
0%
|
0
0%
|
1
3.3%
|
1
3.2%
|
| Glucose >=11.1 mmol/L (unfas) or >=7 mmol/L (fas) |
0
0%
|
1
6.7%
|
0
0%
|
2
6.5%
|
| HbA1c >8% |
0
0%
|
0
0%
|
0
0%
|
1
3.2%
|
| Total Cholesterol >=6.2 mmol/L |
6
40%
|
7
46.7%
|
12
40%
|
13
41.9%
|
| Total Cholesterol >=7.74 mmol/L |
1
6.7%
|
1
6.7%
|
1
3.3%
|
2
6.5%
|
| LDL Cholesterol >=4.1 mmol/L |
1
6.7%
|
3
20%
|
6
20%
|
3
9.7%
|
| LDL Cholesterol >=4.9 mmol/L |
0
0%
|
1
6.7%
|
2
6.7%
|
1
3.2%
|
| Triglycerides >=4.6 mmol/L |
0
0%
|
0
0%
|
0
0%
|
1
3.2%
|
| Triglycerides >=5.6 mmol/L |
0
0%
|
0
0%
|
0
0%
|
1
3.2%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomized participants who actually received at least one dose or a partial dose of IMP analyzed according to the treatment actually received. |
| Arm/Group Title | Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w | Sarilumab 200 mg q2w |
|---|---|---|---|---|
| Arm/Group Description | Participants received sarilumab 150 mg, SC injection, q2w along with non-MTX DMARDs for up to 52 weeks. | Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs 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. |
| Measure Participants | 15 | 15 | 30 | 31 |
| Sodium <=129 mmol/L |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Sodium >=160 mmol/L |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Potassium <3 mmol/L |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Potassium >=5.5 mmol/L |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Chloride <80 mmol/L |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Chloride >115 mmol/L |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters |
|---|---|
| Description | 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 |
| Time Frame | Baseline up to Week 58 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomized participants who actually received at least one dose or a partial dose of IMP analyzed according to the treatment actually received. |
| Arm/Group Title | Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w | Sarilumab 200 mg q2w |
|---|---|---|---|---|
| Arm/Group Description | Participants received sarilumab 150 mg, SC injection, q2w along with non-MTX DMARDs for up to 52 weeks. | Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs 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. |
| Measure Participants | 15 | 15 | 30 | 31 |
| Creatinine >=150 micromol/L (Adults) |
0
0%
|
0
0%
|
0
0%
|
1
3.2%
|
| Creatinine >=30% change from baseline |
3
20%
|
3
20%
|
6
20%
|
5
16.1%
|
| Creatinine >=100% change from baseline |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Creatinine Clearance <15 mL/min |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Creatinine clearance >=15 to <30 mL/min |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Creatinine clearance >=30 to <60 mL/min |
6
40%
|
6
40%
|
6
20%
|
5
16.1%
|
| Creatinine clearance >=60 to <90 mL/min |
8
53.3%
|
7
46.7%
|
15
50%
|
17
54.8%
|
| Blood Urea Nitrogen >=17 mmol/L |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Uric acid <120 micromol/L |
0
0%
|
1
6.7%
|
0
0%
|
0
0%
|
| Uric acid >408 micromol/L |
1
6.7%
|
1
6.7%
|
2
6.7%
|
4
12.9%
|
| Title | Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters |
|---|---|
| Description | 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 |
| Time Frame | Baseline up to Week 58 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety population included all randomized participants who actually received at least one dose or a partial dose of IMP analyzed according to the treatment actually received. |
| Arm/Group Title | Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w | Sarilumab 200 mg q2w |
|---|---|---|---|---|
| Arm/Group Description | Participants received sarilumab 150 mg, SC injection, q2w along with non-MTX DMARDs for up to 52 weeks. | Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs 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. |
| Measure Participants | 15 | 15 | 30 | 31 |
| ALT >1 ULN and <=1.5 ULN |
3
20%
|
4
26.7%
|
7
23.3%
|
6
19.4%
|
| ALT >1.5 ULN and <=3 ULN |
2
13.3%
|
1
6.7%
|
3
10%
|
2
6.5%
|
| ALT >3 ULN and <=5 ULN |
1
6.7%
|
0
0%
|
1
3.3%
|
4
12.9%
|
| ALT >5 ULN and <=10 ULN |
1
6.7%
|
0
0%
|
0
0%
|
0
0%
|
| ALT >10 ULN and <=20 ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ALT >20 ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| AST >1 ULN and <=1.5 ULN |
6
40%
|
5
33.3%
|
8
26.7%
|
4
12.9%
|
| AST >1.5 ULN and <=3 ULN |
1
6.7%
|
0
0%
|
2
6.7%
|
3
9.7%
|
| AST >3 ULN and <=5 ULN |
1
6.7%
|
0
0%
|
0
0%
|
1
3.2%
|
| AST >5 ULN and <=10 ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| AST >10 ULN and <=20 ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| AST >20 ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Alkaline Phosphatase >1.5 ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| TBILI >1.5 ULN |
1
6.7%
|
1
6.7%
|
0
0%
|
0
0%
|
| TBILI >2 ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| CBILI >1.5 ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unconjugated Bilirubin >1.5 ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| ALT> 3 ULN and TBILI >2ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| CBILI >35% TBILI and TBILI >1.5 ULN |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Albumin <=25 g/L |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Adverse Events
| Time Frame | All AEs were collected from signature of the informed consent form until the end of the study (Week 58) regardless of seriousness or relationship to IMP. | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Reported AEs are treatment-emergent AEs that developed/worsened during the 'on treatment period' (from the first IMP administration up to the 6 week after last IMP administration [up to Week 58]). | |||||||
| Arm/Group Title | Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w Monotherapy | Sarilumab 200 mg q2w Monotherapy | ||||
| Arm/Group Description | Participants received sarilumab 150 mg, SC injection, q2w along with non-MTX DMARDs for up to 52 weeks. | Participants received sarilumab 200 mg, SC injection, q2w along with non-MTX DMARDs 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. | ||||
All Cause Mortality |
||||||||
| Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w Monotherapy | Sarilumab 200 mg q2w Monotherapy | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/15 (0%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
Serious Adverse Events |
||||||||
| Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w Monotherapy | Sarilumab 200 mg q2w Monotherapy | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/15 (0%) | 3/15 (20%) | 1/30 (3.3%) | 2/31 (6.5%) | ||||
| Infections and infestations | ||||||||
| Chronic sinusitis | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Herpes zoster oticus | 0/15 (0%) | 0/15 (0%) | 1/30 (3.3%) | 0/31 (0%) | ||||
| Periorbital abscess | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Pneumonia bacterial | 0/15 (0%) | 0/15 (0%) | 0/30 (0%) | 1/31 (3.2%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Breast cancer female | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Gastric cancer | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Surgical and medical procedures | ||||||||
| Abortion induced | 0/15 (0%) | 0/15 (0%) | 0/30 (0%) | 1/31 (3.2%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Sarilumab 150 mg q2w + DMARDs | Sarilumab 200 mg q2w + DMARDs | Sarilumab 150 mg q2w Monotherapy | Sarilumab 200 mg q2w Monotherapy | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/15 (93.3%) | 13/15 (86.7%) | 22/30 (73.3%) | 23/31 (74.2%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Neutropenia | 5/15 (33.3%) | 3/15 (20%) | 1/30 (3.3%) | 3/31 (9.7%) | ||||
| Thrombocytopenia | 1/15 (6.7%) | 1/15 (6.7%) | 0/30 (0%) | 1/31 (3.2%) | ||||
| Eye disorders | ||||||||
| Conjunctivitis allergic | 0/15 (0%) | 0/15 (0%) | 0/30 (0%) | 2/31 (6.5%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain upper | 0/15 (0%) | 0/15 (0%) | 0/30 (0%) | 2/31 (6.5%) | ||||
| Constipation | 0/15 (0%) | 1/15 (6.7%) | 1/30 (3.3%) | 1/31 (3.2%) | ||||
| Gastritis | 0/15 (0%) | 0/15 (0%) | 2/30 (6.7%) | 0/31 (0%) | ||||
| Glossodynia | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| Stomatitis | 3/15 (20%) | 4/15 (26.7%) | 3/30 (10%) | 4/31 (12.9%) | ||||
| General disorders | ||||||||
| Injection site erythema | 0/15 (0%) | 1/15 (6.7%) | 1/30 (3.3%) | 6/31 (19.4%) | ||||
| Injection site haemorrhage | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| Injection site pruritus | 0/15 (0%) | 1/15 (6.7%) | 1/30 (3.3%) | 1/31 (3.2%) | ||||
| Injection site rash | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| Injection site swelling | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 2/31 (6.5%) | ||||
| Oedema peripheral | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| Hepatobiliary disorders | ||||||||
| Hepatic function abnormal | 1/15 (6.7%) | 0/15 (0%) | 1/30 (3.3%) | 4/31 (12.9%) | ||||
| Infections and infestations | ||||||||
| Bronchitis | 0/15 (0%) | 1/15 (6.7%) | 1/30 (3.3%) | 0/31 (0%) | ||||
| Chronic sinusitis | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Conjunctivitis | 1/15 (6.7%) | 0/15 (0%) | 1/30 (3.3%) | 0/31 (0%) | ||||
| Enteritis infectious | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| Gastroenteritis | 2/15 (13.3%) | 0/15 (0%) | 1/30 (3.3%) | 1/31 (3.2%) | ||||
| Gingivitis | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| Nasopharyngitis | 4/15 (26.7%) | 5/15 (33.3%) | 13/30 (43.3%) | 14/31 (45.2%) | ||||
| Periodontitis | 0/15 (0%) | 1/15 (6.7%) | 2/30 (6.7%) | 0/31 (0%) | ||||
| Pharyngitis | 0/15 (0%) | 1/15 (6.7%) | 1/30 (3.3%) | 0/31 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Accidental overdose | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Contusion | 3/15 (20%) | 0/15 (0%) | 2/30 (6.7%) | 0/31 (0%) | ||||
| Foot fracture | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Heat stroke | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| Scratch | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 1/15 (6.7%) | 0/15 (0%) | 1/30 (3.3%) | 1/31 (3.2%) | ||||
| Neutrophil count decreased | 1/15 (6.7%) | 1/15 (6.7%) | 2/30 (6.7%) | 1/31 (3.2%) | ||||
| Protein urine | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Weight increased | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| White blood cell count decreased | 1/15 (6.7%) | 1/15 (6.7%) | 0/30 (0%) | 1/31 (3.2%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Hypercholesterolaemia | 0/15 (0%) | 0/15 (0%) | 1/30 (3.3%) | 2/31 (6.5%) | ||||
| Hyperlipidaemia | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Muscle spasms | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| Musculoskeletal stiffness | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| Myalgia | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| Neck pain | 1/15 (6.7%) | 0/15 (0%) | 1/30 (3.3%) | 0/31 (0%) | ||||
| Osteoarthritis | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| Osteoporosis | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Rheumatoid arthritis | 1/15 (6.7%) | 0/15 (0%) | 4/30 (13.3%) | 2/31 (6.5%) | ||||
| Synovitis | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Breast cancer female | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Gastric cancer | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 0/15 (0%) | 2/15 (13.3%) | 2/30 (6.7%) | 1/31 (3.2%) | ||||
| Dysarthria | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Sciatica | 1/15 (6.7%) | 0/15 (0%) | 1/30 (3.3%) | 0/31 (0%) | ||||
| Psychiatric disorders | ||||||||
| Insomnia | 1/15 (6.7%) | 1/15 (6.7%) | 0/30 (0%) | 1/31 (3.2%) | ||||
| Renal and urinary disorders | ||||||||
| Haematuria | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Renal impairment | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Asthma | 0/15 (0%) | 1/15 (6.7%) | 1/30 (3.3%) | 0/31 (0%) | ||||
| Cough | 0/15 (0%) | 1/15 (6.7%) | 1/30 (3.3%) | 1/31 (3.2%) | ||||
| Epistaxis | 0/15 (0%) | 0/15 (0%) | 2/30 (6.7%) | 0/31 (0%) | ||||
| Oropharyngeal pain | 0/15 (0%) | 0/15 (0%) | 3/30 (10%) | 2/31 (6.5%) | ||||
| Rhinitis allergic | 0/15 (0%) | 0/15 (0%) | 0/30 (0%) | 2/31 (6.5%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Alopecia | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| Dermatitis contact | 0/15 (0%) | 0/15 (0%) | 2/30 (6.7%) | 1/31 (3.2%) | ||||
| Eczema | 0/15 (0%) | 1/15 (6.7%) | 1/30 (3.3%) | 2/31 (6.5%) | ||||
| Eczema nummular | 1/15 (6.7%) | 0/15 (0%) | 1/30 (3.3%) | 0/31 (0%) | ||||
| Haemorrhage subcutaneous | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 1/31 (3.2%) | ||||
| Onycholysis | 1/15 (6.7%) | 0/15 (0%) | 0/30 (0%) | 0/31 (0%) | ||||
| Pruritus | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Psoriasis | 0/15 (0%) | 1/15 (6.7%) | 0/30 (0%) | 0/31 (0%) | ||||
| Rash | 1/15 (6.7%) | 1/15 (6.7%) | 1/30 (3.3%) | 0/31 (0%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 0/15 (0%) | 1/15 (6.7%) | 1/30 (3.3%) | 1/31 (3.2%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
| Name/Title | Trial Transparency Team |
|---|---|
| Organization | Sanofi |
| Phone | |
| Contact-US@sanofi.com |
Responsible Party:
Sanofi
ClinicalTrials.gov Identifier:
NCT02373202
Other Study ID Numbers:
- LTS13618
- U1111-1160-6525
First Posted:
Feb 26, 2015
Last Update Posted:
Jan 30, 2018
Last Verified:
Jan 1, 2018