SARIL-RA-EASY: To Evaluate Sarilumab - SAR153191 (REGN88) - Auto-injector Device In Patients With Rheumatoid Arthritis

• Sponsor: Sanofi (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02057250
• Collaborator: Regeneron Pharmaceuticals (Industry)
• Enrollment: 217
• Locations: 53
• Arms: 4
• Duration (Months): 24
• Patients Per Site: 4.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Primary Objective:

To collect real-use data of the sarilumab auto-injector device (AID) used by rheumatoid arthritis (RA) participants.

Secondary Objective:

To compare the pharmacokinetic (PK) exposure of sarilumab administered by AID versus prefilled syringes (PFS).

Condition or Disease	Intervention/Treatment	Phase
RA	Drug: Sarilumab; Device: Auto-Injector Device (AID); Device: Pre-filled Syringe (PFS); Drug: Methotrexate; Drug: Sulfasalazine; Drug: Leflunomide; Drug: Hydroxychloroquine	Phase 3

Detailed Description

Total study duration up to 74 weeks: screening up to 4 weeks, AID assessment phase of 12 weeks, extension phase of 52 weeks and post-treatment follow-up of 6 weeks.

For participants not entering the extension phase, total study duration up to 22 weeks (screening, AID assessment phase and follow-up).

Study Design

• Study Type: Interventional
• Actual Enrollment: 217 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Open-Label, Parallel-Group Usability Study Of The Sarilumab Auto-Injector Device And A Prefilled Syringe In Patients With Moderate To Severe Active Rheumatoid Arthritis Who Are Candidates For Anti-IL6R Therapy
• Study Start Date: Mar 1, 2014
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: Mar 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sarilumab 150 mg by AID Sarilumab 150 mg subcutaneous (SC) injection every 2 weeks (q2w) administered by AID with one or a combination of non-biologic disease-modifying anti-rheumatic drug (DMARD) (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide, except for simultaneous combination use of leflunomide and methotrexate) in AID assessment phase for 12 weeks. Participants who completed 12 weeks AID assessment phase entered in open-label extension phase and received sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 52 weeks.	Drug: Sarilumab; Pharmaceutical form: Solution Route of administration: Subcutaneous; Other Names: SAR153191 REGN88 ; Device: Auto-Injector Device (AID); Drug: Methotrexate; Dispensed according to local practice.; Drug: Sulfasalazine; Dispensed according to local practice.; Drug: Leflunomide; Dispensed according to local practice.; Drug: Hydroxychloroquine; Dispensed according to local practice.
Experimental: Sarilumab 150 mg by PFS Sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide, except for simultaneous combination use of leflunomide and methotrexate) in AID assessment phase for 12 weeks. Participants who completed 12 weeks AID assessment phase entered in open-label extension phase and received sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 52 weeks.	Drug: Sarilumab; Pharmaceutical form: Solution Route of administration: Subcutaneous; Other Names: SAR153191 REGN88 ; Device: Pre-filled Syringe (PFS); Drug: Methotrexate; Dispensed according to local practice.; Drug: Sulfasalazine; Dispensed according to local practice.; Drug: Leflunomide; Dispensed according to local practice.; Drug: Hydroxychloroquine; Dispensed according to local practice.
Experimental: Sarilumab 200 mg by AID Sarilumab 200 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide, except for simultaneous combination use of leflunomide and methotrexate) in AID assessment phase for 12 weeks. Participants who completed 12 weeks AID assessment phase entered in open-label extension phase and received sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 52 weeks.	Drug: Sarilumab; Pharmaceutical form: Solution Route of administration: Subcutaneous; Other Names: SAR153191 REGN88 ; Device: Auto-Injector Device (AID); Drug: Methotrexate; Dispensed according to local practice.; Drug: Sulfasalazine; Dispensed according to local practice.; Drug: Leflunomide; Dispensed according to local practice.; Drug: Hydroxychloroquine; Dispensed according to local practice.
Experimental: Sarilumab 200 mg by PFS Sarilumab 200 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD (hydroxychloroquine, methotrexate, sulfasalazine and/or Leflunomide, except for simultaneous combination use of leflunomide and methotrexate) in AID assessment phase for 12 weeks. Participants who completed 12 weeks AID assessment phase entered in open-label extension phase and received sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 52 weeks.	Drug: Sarilumab; Pharmaceutical form: Solution Route of administration: Subcutaneous; Other Names: SAR153191 REGN88 ; Device: Pre-filled Syringe (PFS); Drug: Methotrexate; Dispensed according to local practice.; Drug: Sulfasalazine; Dispensed according to local practice.; Drug: Leflunomide; Dispensed according to local practice.; Drug: Hydroxychloroquine; Dispensed according to local practice.

Outcome Measures

Primary Outcome Measures

1. Number of Validated AID Associated Product Technical Failures (PTFs) [Baseline up to Week 12]

   A PTF was defined as any product technical complaint (PTC) related to the use of the AID that had a validated technical cause. Each participant was given a diary having questions related to participant's ability to remove the cap, to start the injection, to complete the injection and regarding confirmation of completing the injection. Participants were asked to answer the questions each time they self-inject the sarilumab. If the response was "no" to any of the first 3 questions, this was considered as a PTC. The used AID, for which PTC was reported, was sent to sponsor, examined and evaluated for the occurrence of a PTF.

Secondary Outcome Measures

1. Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab [Week 0-2: pre-dose on Day 1, anytime post-dose on Day 3, Day 5, Day 8, Day 12, Day 15; Week 10-12: pre-dose on Day 71, anytime post-dose on Day 73, Day 75, Day 78, Day 82, Day 85]

   AUC(0-tau) is defined as area under the serum concentration versus time curve calculated using the trapezoidal method during a dose interval, where dose interval was 2 weeks. Serum concentrations of sarilumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Diagnosis of RA, ≥3 months disease duration;

• Participant willing and able to self-inject;

• Continuous treatment with 1 or a combination of non-biologic disease modifying antirheumatic drugs (DMARDs) (except leflunomide in combination with methotrexate);

• Moderate-to-severely active RA.

Exclusion criteria:

• Participants <18 years;

• Prior treatment with anti-interleukin 6 (IL-6) or IL-6 receptor (IL-6R) antagonists;

• Treatment with tumor necrosis factor (TNF) antagonists;

• Treatment with RA-directed biologic agents other than with a TNF-α antagonist mechanism as follows: Anakinra, Abatacept, Rituximab or other cell-depleting agent;

• Prior treatment with a Janus kinase inhibitor.

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 840152	Huntsville	Alabama	United States	35801
2	Investigational Site Number 840221	Peoria	Arizona	United States	85381
3	Investigational Site Number 840226	Roseville	California	United States	95661
4	Investigational Site Number 840223	Boulder	Colorado	United States	80304
5	Investigational Site Number 840229	Miami	Florida	United States	33185
6	Investigational Site Number 840236	Orlando	Florida	United States	32804
7	Investigational Site Number 840155	Palm Harbor	Florida	United States	34684
8	Investigational Site Number 840220	South Miami	Florida	United States	33143
9	Investigational Site Number 840202	Hagerstown	Maryland	United States	21740
10	Investigational Site Number 840232	Flint	Michigan	United States	48504
11	Investigational Site Number 840233	Kalamazoo	Michigan	United States	49048
12	Investigational Site Number 840037	Tupelo	Mississippi	United States	38801
13	Investigational Site Number 840112	Lincoln	Nebraska	United States	68516
14	Investigational Site Number 840039	Albany	New York	United States	12208
15	Investigational Site Number 840224	Cincinnati	Ohio	United States	45219
16	Investigational Site Number 840002	Oklahoma City	Oklahoma	United States	73103
17	Investigational Site Number 840065	Tulsa	Oklahoma	United States	74135
18	Investigational Site Number 840009	Duncansville	Pennsylvania	United States	16635
19	Investigational Site Number 840062	Reading	Pennsylvania	United States	19611
20	Investigational Site Number 840016	North Charleston	South Carolina	United States	29406
21	Investigational Site Number 840025	Jackson	Tennessee	United States	38305
22	Investigational Site Number 840038	Austin	Texas	United States	78705
23	Investigational Site Number 840230	Carrollton	Texas	United States	75007
24	Investigational Site Number 840001	Dallas	Texas	United States	75231
25	Investigational Site Number 840020	Houston	Texas	United States	77034
26	Investigational Site Number 840239	Houston	Texas	United States	77034
27	Investigational Site Number 840241	Houston	Texas	United States	77034
28	Investigational Site Number 840242	Houston	Texas	United States	77034
29	Investigational Site Number 840069	Lubbock	Texas	United States	79424
30	Investigational Site Number 840074	Mesquite	Texas	United States	75150
31	Investigational Site Number 840237	Plano	Texas	United States	75042
32	Investigational Site Number 152005	Osorno		Chile	5311092
33	Investigational Site Number 152050	Santiago		Chile
34	Investigational Site Number 152014	Talca		Chile
35	Investigational Site Number 152007	Viña Del Mar		Chile	2520997
36	Investigational Site Number 484002	Guadalajara		Mexico	44690
37	Investigational Site Number 484004	Merida		Mexico	97000
38	Investigational Site Number 484005	Monterrey		Mexico	64460
39	Investigational Site Number 616002	Bialystok		Poland	15-351
40	Investigational Site Number 616005	Lublin		Poland	20-582
41	Investigational Site Number 616004	Warszawa		Poland	02-118
42	Investigational Site Number 616017	Warszawa		Poland	02-653
43	Investigational Site Number 616012	Wroclaw		Poland	50-044
44	Investigational Site Number 643006	Kemerovo		Russian Federation	650000
45	Investigational Site Number 643020	Moscow		Russian Federation	115404
46	Investigational Site Number 643001	Moscow		Russian Federation	115522
47	Investigational Site Number 643008	Saint-Petersburg		Russian Federation	192242
48	Investigational Site Number 710050	Bellville		South Africa	7530
49	Investigational Site Number 710011	Cape Town		South Africa	7405
50	Investigational Site Number 710007	Cape Town		South Africa	7500
51	Investigational Site Number 710003	Durban		South Africa	4001
52	Investigational Site Number 710001	Johannesburg		South Africa	2013
53	Investigational Site Number 710051	Port Elizabeth		South Africa	6045

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: NCT02057250
• Other Study ID Numbers: MSC12665; 2012-004339-21; U1111-1130-9931
• First Posted: Feb 7, 2014
• Last Update Posted: Jun 20, 2017
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Hydroxychloroquine; Sulfasalazine; Methotrexate; Leflunomide

Study Results

Participant Flow

Recruitment Details	The study was conducted at 53 centers in 6 countries. A total of 419 participants were screened between 18 March 2014 and 14 October 2014, out of which 217 participants were enrolled and treated.
Pre-assignment Detail	Participants were randomized in 1:1:1:1 ratio to Sarilumab 150 mg administered by auto-injector device (AID) or prefilled syringe (PFS) or Sarilumab 200 mg administered by AID or PFS. Participants who completed 12-week AID assessment phase, were treated in open-label extension phase for 52 weeks.

Arm/Group Title	Sarilumab 150 mg by AID (AID Assessment Phase)	Sarilumab 150 mg by PFS (AID Assessment Phase)	Sarilumab 200 mg by AID (AID Assessment Phase)	Sarilumab 200 mg by PFS (AID Assessment Phase)	Sarilumab 150 mg by PFS (Extension Phase)
Arm/Group Description	Sarilumab 150 mg subcutaneous (SC) injection every 2 weeks (q2w) administered by AID with one or a combination of non-biologic disease-modifying anti-rheumatic drug (DMARD) for 12 weeks.	Sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.	Sarilumab 200 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.	Sarilumab 200 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.	Participants who completed 12 week AID assessment phase received Sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 52 weeks.
Period Title: AID Assessment Phase
STARTED	56	53	52	56	0
COMPLETED	52	50	45	54	0
NOT COMPLETED	4	3	7	2	0
Period Title: AID Assessment Phase
STARTED	0	0	0	0	192
Treated	0	0	0	0	188
COMPLETED	0	0	0	0	156
NOT COMPLETED	0	0	0	0	36

Baseline Characteristics

Arm/Group Title	Sarilumab 150 mg by AID (AID Assessment Phase)	Sarilumab 150 mg by PFS (AID Assessment Phase)	Sarilumab 200 mg by AID (AID Assessment Phase)	Sarilumab 200 mg by PFS (AID Assessment Phase)	Total
Arm/Group Description	Sarilumab 150 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.	Sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.	Sarilumab 200 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.	Sarilumab 200 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.	Total of all reporting groups
Overall Participants	56	53	52	56	217
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.7 (13.8)	54.2 (14.2)	55.9 (12.3)	50.3 (12.8)	53.5 (13.4)
Sex: Female, Male (Count of Participants)
Female	45 80.4%	43 81.1%	44 84.6%	49 87.5%	181 83.4%
Male	11 19.6%	10 18.9%	8 15.4%	7 12.5%	36 16.6%

Outcome Measures

1. Primary Outcome

Title	Number of Validated AID Associated Product Technical Failures (PTFs)
Description	A PTF was defined as any product technical complaint (PTC) related to the use of the AID that had a validated technical cause. Each participant was given a diary having questions related to participant's ability to remove the cap, to start the injection, to complete the injection and regarding confirmation of completing the injection. Participants were asked to answer the questions each time they self-inject the sarilumab. If the response was "no" to any of the first 3 questions, this was considered as a PTC. The used AID, for which PTC was reported, was sent to sponsor, examined and evaluated for the occurrence of a PTF.
Time Frame	Baseline up to Week 12

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) population included all randomized participants who received at least 1 dose of investigational medicinal product (IMP) with AID and attended at least 1 post-baseline visit during AID assessment phase of the study.

Arm/Group Title	Sarilumab 150 mg by AID (AID Assessment Phase)	Sarilumab 200 mg by AID (AID Assessment Phase)
Arm/Group Description	Sarilumab 150 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.	Sarilumab 200 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.
Measure Participants	56	52
Measure Injections	312	288
Number [PTFs]	0	0

2. Secondary Outcome

Title	Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab
Description	AUC(0-tau) is defined as area under the serum concentration versus time curve calculated using the trapezoidal method during a dose interval, where dose interval was 2 weeks. Serum concentrations of sarilumab were analyzed using validated enzyme linked immunosorbent assay (ELISA).
Time Frame	Week 0-2: pre-dose on Day 1, anytime post-dose on Day 3, Day 5, Day 8, Day 12, Day 15; Week 10-12: pre-dose on Day 71, anytime post-dose on Day 73, Day 75, Day 78, Day 82, Day 85

Outcome Measure Data

Analysis Population Description

Pharmacokinetic(PK) population included all randomized participants who received at least 1 dose of IMP and have least 1 PK parameter calculated using non compartmental methods following the first (Day 1) or sixth administration (Day 71). Here, Number Analyzed = participants with available data for specified category for each arm, respectively.

Arm/Group Title	Sarilumab 150 mg by AID (AID Assessment Phase)	Sarilumab 150 mg by PFS (AID Assessment Phase)	Sarilumab 200 mg by AID (AID Assessment Phase)	Sarilumab 200 mg by PFS (AID Assessment Phase)
Arm/Group Description	Sarilumab 150 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.	Sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.	Sarilumab 200 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.	Sarilumab 200 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.
Measure Participants	56	53	52	56
Week 0-2	131 (54.5)	152 (76.7)	235 (117)	227 (94.9)
Week 10-12	205 (126)	220 (130)	455 (294)	405 (244)

Adverse Events

Time Frame	All Adverse Events (AEs) were collected from signature of the informed consent form up to the final visit (74 Weeks) regardless of seriousness or relationship to study drug.
Adverse Event Reporting Description	Reported AEs are treatment-emergent AEs developed/worsened during 'on treatment period' (time from first dose of IMP in AID assessment phase up to last dose of IMP in extension phase + 6 weeks). Safety population of AID assessment phase included all randomized participants who received at least 1 dose or part of a dose of IMP and safety population of extension phase included all participants who continued in the extension phase and received at least 1 dose or part of a dose of IMP.
Arm/Group Title	Sarilumab 150 mg by AID (AID Assessment Phase)		Sarilumab 150 mg by PFS (AID Assessment Phase)		Sarilumab 200 mg by AID (AID Assessment Phase)		Sarilumab 200 mg by PFS (AID Assessment Phase)		Sarilumab 150 mg by PFS (Extension Phase)
Arm/Group Description	Sarilumab 150 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.		Sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.		Sarilumab 200 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.		Sarilumab 200 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.		Participants who completed 12 week AID assessment phase received Sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 52 weeks.
All Cause Mortality
	Sarilumab 150 mg by AID (AID Assessment Phase)		Sarilumab 150 mg by PFS (AID Assessment Phase)		Sarilumab 200 mg by AID (AID Assessment Phase)		Sarilumab 200 mg by PFS (AID Assessment Phase)		Sarilumab 150 mg by PFS (Extension Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Sarilumab 150 mg by AID (AID Assessment Phase)		Sarilumab 150 mg by PFS (AID Assessment Phase)		Sarilumab 200 mg by AID (AID Assessment Phase)		Sarilumab 200 mg by PFS (AID Assessment Phase)		Sarilumab 150 mg by PFS (Extension Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/56 (1.8%)		0/53 (0%)		3/52 (5.8%)		4/56 (7.1%)		19/188 (10.1%)
Blood and lymphatic system disorders
Anaemia	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Cardiac disorders
Coronary artery occlusion	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Wolff-Parkinson-White syndrome	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Eye disorders
Cataract	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Gastrointestinal disorders
Small intestinal obstruction	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Vomiting	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Hepatobiliary disorders
Bile duct stone	0/56 (0%)		0/53 (0%)		1/52 (1.9%)		0/56 (0%)		0/188 (0%)
Cholelithiasis	0/56 (0%)		0/53 (0%)		0/52 (0%)		1/56 (1.8%)		0/188 (0%)
Infections and infestations
Bursitis infective staphylococcal	1/56 (1.8%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		0/188 (0%)
Cellulitis	0/56 (0%)		0/53 (0%)		0/52 (0%)		1/56 (1.8%)		0/188 (0%)
Erysipelas	0/56 (0%)		0/53 (0%)		0/52 (0%)		1/56 (1.8%)		0/188 (0%)
Pneumonia	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Urinary tract infection	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Injury, poisoning and procedural complications
Femoral neck fracture	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Traumatic arthritis	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Lumbar spinal stenosis	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Osteoarthritis	0/56 (0%)		0/53 (0%)		1/52 (1.9%)		0/56 (0%)		1/188 (0.5%)
Rheumatoid arthritis	0/56 (0%)		0/53 (0%)		1/52 (1.9%)		0/56 (0%)		0/188 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma metastatic	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Squamous cell carcinoma of skin	0/56 (0%)		0/53 (0%)		0/52 (0%)		1/56 (1.8%)		0/188 (0%)
Nervous system disorders
Transient ischaemic attack	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Vertebrobasilar insufficiency	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Renal and urinary disorders
Nephrolithiasis	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Reproductive system and breast disorders
Endometrial hyperplasia	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Rheumatoid lung	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Vascular disorders
Deep vein thrombosis	0/56 (0%)		0/53 (0%)		1/52 (1.9%)		0/56 (0%)		0/188 (0%)
Thrombophlebitis superficial	0/56 (0%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Other (Not Including Serious) Adverse Events
	Sarilumab 150 mg by AID (AID Assessment Phase)		Sarilumab 150 mg by PFS (AID Assessment Phase)		Sarilumab 200 mg by AID (AID Assessment Phase)		Sarilumab 200 mg by PFS (AID Assessment Phase)		Sarilumab 150 mg by PFS (Extension Phase)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/56 (51.8%)		21/53 (39.6%)		24/52 (46.2%)		23/56 (41.1%)		83/188 (44.1%)
Blood and lymphatic system disorders
Leukopenia	3/56 (5.4%)		2/53 (3.8%)		0/52 (0%)		0/56 (0%)		1/188 (0.5%)
Neutropenia	10/56 (17.9%)		9/53 (17%)		6/52 (11.5%)		4/56 (7.1%)		12/188 (6.4%)
Thrombocytopenia	4/56 (7.1%)		1/53 (1.9%)		2/52 (3.8%)		1/56 (1.8%)		3/188 (1.6%)
Gastrointestinal disorders
Nausea	1/56 (1.8%)		0/53 (0%)		0/52 (0%)		3/56 (5.4%)		0/188 (0%)
General disorders
Injection site erythema	2/56 (3.6%)		2/53 (3.8%)		4/52 (7.7%)		4/56 (7.1%)		7/188 (3.7%)
Injection site pruritus	1/56 (1.8%)		2/53 (3.8%)		0/52 (0%)		4/56 (7.1%)		5/188 (2.7%)
Infections and infestations
Bronchitis	4/56 (7.1%)		1/53 (1.9%)		1/52 (1.9%)		1/56 (1.8%)		8/188 (4.3%)
Nasopharyngitis	4/56 (7.1%)		1/53 (1.9%)		1/52 (1.9%)		2/56 (3.6%)		4/188 (2.1%)
Pharyngitis	5/56 (8.9%)		0/53 (0%)		1/52 (1.9%)		1/56 (1.8%)		2/188 (1.1%)
Sinusitis	1/56 (1.8%)		3/53 (5.7%)		0/52 (0%)		1/56 (1.8%)		12/188 (6.4%)
Upper respiratory tract infection	3/56 (5.4%)		2/53 (3.8%)		1/52 (1.9%)		3/56 (5.4%)		25/188 (13.3%)
Urinary tract infection	2/56 (3.6%)		2/53 (3.8%)		2/52 (3.8%)		2/56 (3.6%)		10/188 (5.3%)
Injury, poisoning and procedural complications
Accidental overdose	0/56 (0%)		0/53 (0%)		2/52 (3.8%)		3/56 (5.4%)		8/188 (4.3%)
Contusion	3/56 (5.4%)		0/53 (0%)		0/52 (0%)		0/56 (0%)		3/188 (1.6%)
Investigations
Alanine aminotransferase increased	1/56 (1.8%)		1/53 (1.9%)		5/52 (9.6%)		1/56 (1.8%)		9/188 (4.8%)
Vascular disorders
Hypertension	2/56 (3.6%)		1/53 (1.9%)		3/52 (5.8%)		2/56 (3.6%)		1/188 (0.5%)

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.