To Evaluate Sarilumab - SAR153191 (REGN88) - Auto-injecto... | NCT02057250

ID	Type	Description	Link
2012-004339-21
U1111-1130-9931	Other Identifier	UTN

Status Module

Name	Class
Regeneron Pharmaceuticals	INDUSTRY

Oversight Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Sarilumab 150 mg by AID	Experimental	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 Device: Auto-Injector Device (AID) Drug: Methotrexate Drug: Sulfasalazine Drug: Leflunomide Drug: Hydroxychloroquine
Sarilumab 150 mg by PFS	Experimental	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 Device: Pre-filled Syringe (PFS) Drug: Methotrexate Drug: Sulfasalazine Drug: Leflunomide Drug: Hydroxychloroquine
Sarilumab 200 mg by AID	Experimental	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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Sarilumab	Drug	Pharmaceutical form: Solution Route of administration: Subcutaneous	Sarilumab 150 mg by AID Sarilumab 150 mg by PFS Sarilumab 200 mg by AID

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Validated AID Associated Product Technical Failures (PTFs)	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.	Baseline up to Week 12

Secondary Outcomes

Measure	Description	Time Frame
Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab	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 Module

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 840152		Huntsville	Alabama	35801	United States
Investigational Site Number 840221

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
29209946	Derived	Kivitz A, Baret-Cormel L, van Hoogstraten H, Wang S, Parrino J, Xu C, Stanislav M. Usability and Patient Preference Phase 3 Study of the Sarilumab Pen in Patients with Active Moderate-to-Severe Rheumatoid Arthritis. Rheumatol Ther. 2018 Jun;5(1):231-242. doi: 10.1007/s40744-017-0090-2. Epub 2017 Dec 5.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Sarilumab 150 mg by AID (AID Assessment Phase)	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.
FG001	Sarilumab 150 mg by PFS (AID Assessment Phase)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Sarilumab 150 mg by AID (AID Assessment Phase)	Sarilumab 150 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.
BG001	Sarilumab 150 mg by PFS (AID Assessment Phase)	Sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.
BG002	Sarilumab 200 mg by AID (AID Assessment Phase)	Sarilumab 200 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.
BG003	Sarilumab 200 mg by PFS (AID Assessment Phase)	Sarilumab 200 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.
BG004	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Validated AID Associated Product Technical Failures (PTFs)

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.

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.

Posted

Number

PTFs

Baseline up to Week 12

Injections

ID	Title	Description
OG000	Sarilumab 150 mg by AID (AID Assessment Phase)	Sarilumab 150 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.
OG001	Sarilumab 200 mg by AID (AID Assessment Phase)	Sarilumab 200 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.

Units	Counts
Participants	OG00056 OG00152
Injections	OG000312 OG001

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010

Secondary

Area Under the Serum Concentration Versus Time Curve Calculated Using the Trapezoidal Method During a Dose Interval (AUC[0-tau]) for Sarilumab

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).

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.

Posted

Mean

Standard Deviation

mg*day/L

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

ID	Title	Description
OG000	Sarilumab 150 mg by AID (AID Assessment Phase)	Sarilumab 150 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.
OG001	Sarilumab 150 mg by PFS (AID Assessment Phase)	Sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Sarilumab 150 mg by AID (AID Assessment Phase)	Sarilumab 150 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.	1	56	29	56
EG001	Sarilumab 150 mg by PFS (AID Assessment Phase)	Sarilumab 150 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.	0	53	21	53
EG002	Sarilumab 200 mg by AID (AID Assessment Phase)	Sarilumab 200 mg SC injection q2w administered by AID with one or a combination of non-biologic DMARD for 12 weeks.	3	52	24	52
EG003	Sarilumab 200 mg by PFS (AID Assessment Phase)	Sarilumab 200 mg SC injection q2w administered by PFS with one or a combination of non-biologic DMARD for 12 weeks.	4	56	23	56
EG004	Sarilumab 150 mg by PFS (Extension Phase)	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.	19	188	83	188

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bursitis infective staphylococcal	Infections and infestations	MedDra 18.1	Systematic Assessment	EG0001 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG0030 affected56 at risk EG004
Cellulitis	Infections and infestations	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Erysipelas	Infections and infestations	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Pneumonia	Infections and infestations	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Urinary tract infection	Infections and infestations	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Pancreatic carcinoma metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Vertebrobasilar insufficiency	Nervous system disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Cataract	Eye disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Coronary artery occlusion	Cardiac disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Wolff-Parkinson-White syndrome	Cardiac disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0021 affected52 at risk EG003
Thrombophlebitis superficial	Vascular disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Rheumatoid lung	Respiratory, thoracic and mediastinal disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Vomiting	Gastrointestinal disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Bile duct stone	Hepatobiliary disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0021 affected52 at risk EG003
Cholelithiasis	Hepatobiliary disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Lumbar spinal stenosis	Musculoskeletal and connective tissue disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0021 affected52 at risk EG003
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0021 affected52 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Endometrial hyperplasia	Reproductive system and breast disorders	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Femoral neck fracture	Injury, poisoning and procedural complications	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Traumatic arthritis	Injury, poisoning and procedural complications	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Bronchitis	Infections and infestations	MedDra 18.1	Systematic Assessment	EG0004 affected56 at risk EG0011 affected53 at risk EG0021 affected52 at risk EG0031 affected56 at risk EG0048 affected188 at risk
Nasopharyngitis	Infections and infestations	MedDra 18.1	Systematic Assessment	EG0004 affected56 at risk EG0011 affected53 at risk EG0021 affected52 at risk EG003
Pharyngitis	Infections and infestations	MedDra 18.1	Systematic Assessment	EG0005 affected56 at risk EG0010 affected53 at risk EG0021 affected52 at risk EG003
Sinusitis	Infections and infestations	MedDra 18.1	Systematic Assessment	EG0001 affected56 at risk EG0013 affected53 at risk EG0020 affected52 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDra 18.1	Systematic Assessment	EG0003 affected56 at risk EG0012 affected53 at risk EG0021 affected52 at risk EG003
Urinary tract infection	Infections and infestations	MedDra 18.1	Systematic Assessment	EG0002 affected56 at risk EG0012 affected53 at risk EG0022 affected52 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDra 18.1	Systematic Assessment	EG0003 affected56 at risk EG0012 affected53 at risk EG0020 affected52 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDra 18.1	Systematic Assessment	EG00010 affected56 at risk EG0019 affected53 at risk EG0026 affected52 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDra 18.1	Systematic Assessment	EG0004 affected56 at risk EG0011 affected53 at risk EG0022 affected52 at risk EG003
Hypertension	Vascular disorders	MedDra 18.1	Systematic Assessment	EG0002 affected56 at risk EG0011 affected53 at risk EG0023 affected52 at risk EG003
Nausea	Gastrointestinal disorders	MedDra 18.1	Systematic Assessment	EG0001 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003
Injection site erythema	General disorders	MedDra 18.1	Systematic Assessment	EG0002 affected56 at risk EG0012 affected53 at risk EG0024 affected52 at risk EG003
Injection site pruritus	General disorders	MedDra 18.1	Systematic Assessment	EG0001 affected56 at risk EG0012 affected53 at risk EG0020 affected52 at risk EG003
Alanine aminotransferase increased	Investigations	MedDra 18.1	Systematic Assessment	EG0001 affected56 at risk EG0011 affected53 at risk EG0025 affected52 at risk EG003
Accidental overdose	Injury, poisoning and procedural complications	MedDra 18.1	Systematic Assessment	EG0000 affected56 at risk EG0010 affected53 at risk EG0022 affected52 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDra 18.1	Systematic Assessment	EG0003 affected56 at risk EG0010 affected53 at risk EG0020 affected52 at risk EG003

ID	Term
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D013449	Sulfonamides
D000577	Amides
D009930	Organic Chemicals
D013450	Sulfones
D013457	Sulfur Compounds
D007555	Isoxazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D002738	Chloroquine
D000634	Aminoquinolines
D011804	Quinolines

ID	Term
C000592401	sarilumab
D008727	Methotrexate
D012460	Sulfasalazine
D000077339	Leflunomide
D006886	Hydroxychloroquine