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

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

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).

Study Overview

• Status: Completed
• Conditions: RA
• Intervention / Treatment: Drug: Methotrexate; Drug: Sarilumab; Device: Auto-Injector Device (AID); Drug: Sulfasalazine; Drug: Leflunomide; Drug: Hydroxychloroquine; Device: Pre-filled Syringe (PFS)

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 Type: Interventional
• Enrollment (Actual): 217
• Phase: Phase 3

Contacts and Locations

Study Locations

• Chile
  • Osorno, Chile, 5311092
    • Investigational Site Number 152005
  • Santiago, Chile
    • Investigational Site Number 152050
  • Talca, Chile
    • Investigational Site Number 152014
  • Viña Del Mar, Chile, 2520997
    • Investigational Site Number 152007
• Mexico
  • Guadalajara, Mexico, 44690
    • Investigational Site Number 484002
  • Merida, Mexico, 97000
    • Investigational Site Number 484004
  • Monterrey, Mexico, 64460
    • Investigational Site Number 484005
• Poland
  • Bialystok, Poland, 15-351
    • Investigational Site Number 616002
  • Lublin, Poland, 20-582
    • Investigational Site Number 616005
  • Warszawa, Poland, 02-118
    • Investigational Site Number 616004
  • Warszawa, Poland, 02-653
    • Investigational Site Number 616017
  • Wroclaw, Poland, 50-044
    • Investigational Site Number 616012
• Russian Federation
  • Kemerovo, Russian Federation, 650000
    • Investigational Site Number 643006
  • Moscow, Russian Federation, 115404
    • Investigational Site Number 643020
  • Moscow, Russian Federation, 115522
    • Investigational Site Number 643001
  • Saint-Petersburg, Russian Federation, 192242
    • Investigational Site Number 643008
• South Africa
  • Bellville, South Africa, 7530
    • Investigational Site Number 710050
  • Cape Town, South Africa, 7405
    • Investigational Site Number 710011
  • Cape Town, South Africa, 7500
    • Investigational Site Number 710007
  • Durban, South Africa, 4001
    • Investigational Site Number 710003
  • Johannesburg, South Africa, 2013
    • Investigational Site Number 710001
  • Port Elizabeth, South Africa, 6045
    • Investigational Site Number 710051
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Investigational Site Number 840152
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Investigational Site Number 840221
  • California
    • Roseville, California, United States, 95661
      • Investigational Site Number 840226
  • Colorado
    • Boulder, Colorado, United States, 80304
      • Investigational Site Number 840223
  • Florida
    • Miami, Florida, United States, 33185
      • Investigational Site Number 840229
    • Orlando, Florida, United States, 32804
      • Investigational Site Number 840236
    • Palm Harbor, Florida, United States, 34684
      • Investigational Site Number 840155
    • South Miami, Florida, United States, 33143
      • Investigational Site Number 840220
  • Maryland
    • Hagerstown, Maryland, United States, 21740
      • Investigational Site Number 840202
  • Michigan
    • Flint, Michigan, United States, 48504
      • Investigational Site Number 840232
    • Kalamazoo, Michigan, United States, 49048
      • Investigational Site Number 840233
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Investigational Site Number 840037
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • Investigational Site Number 840112
  • New York
    • Albany, New York, United States, 12208
      • Investigational Site Number 840039
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Investigational Site Number 840224
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Investigational Site Number 840002
    • Tulsa, Oklahoma, United States, 74135
      • Investigational Site Number 840065
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Investigational Site Number 840009
    • Reading, Pennsylvania, United States, 19611
      • Investigational Site Number 840062
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Investigational Site Number 840016
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Investigational Site Number 840025
  • Texas
    • Austin, Texas, United States, 78705
      • Investigational Site Number 840038
    • Carrollton, Texas, United States, 75007
      • Investigational Site Number 840230
    • Dallas, Texas, United States, 75231
      • Investigational Site Number 840001
    • Houston, Texas, United States, 77034
      • Investigational Site Number 840020
    • Houston, Texas, United States, 77034
      • Investigational Site Number 840239
    • Houston, Texas, United States, 77034
      • Investigational Site Number 840241
    • Houston, Texas, United States, 77034
      • Investigational Site Number 840242
    • Lubbock, Texas, United States, 79424
      • Investigational Site Number 840069
    • Mesquite, Texas, United States, 75150
      • Investigational Site Number 840074
    • Plano, Texas, United States, 75042
      • Investigational Site Number 840237

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / 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: Methotrexate; Dispensed according to local practice.; Drug: Sarilumab; Pharmaceutical form: Solution Route of administration: Subcutaneous; Other Names: SAR153191; REGN88; Device: Auto-Injector Device (AID); 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: Methotrexate; Dispensed according to local practice.; Drug: Sarilumab; Pharmaceutical form: Solution Route of administration: Subcutaneous; Other Names: SAR153191; REGN88; Drug: Sulfasalazine; Dispensed according to local practice.; Drug: Leflunomide; Dispensed according to local practice.; Drug: Hydroxychloroquine; Dispensed according to local practice.; Device: Pre-filled Syringe (PFS)
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: Methotrexate; Dispensed according to local practice.; Drug: Sarilumab; Pharmaceutical form: Solution Route of administration: Subcutaneous; Other Names: SAR153191; REGN88; Device: Auto-Injector Device (AID); 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: Methotrexate; Dispensed according to local practice.; Drug: Sarilumab; Pharmaceutical form: Solution Route of administration: Subcutaneous; Other Names: SAR153191; REGN88; Drug: Sulfasalazine; Dispensed according to local practice.; Drug: Leflunomide; Dispensed according to local practice.; Drug: Hydroxychloroquine; Dispensed according to local practice.; Device: Pre-filled Syringe (PFS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 Outcome Measures

Outcome Measure	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).	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

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (ACTUAL): February 1, 2015
• Study Completion (ACTUAL): March 1, 2016

Study Registration Dates

• First Submitted: January 31, 2014
• First Submitted That Met QC Criteria: February 5, 2014
• First Posted (ESTIMATE): February 7, 2014

Study Record Updates

• Last Update Posted (ACTUAL): June 20, 2017
• Last Update Submitted That Met QC Criteria: May 23, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Dermatologic Agents; Reproductive Control Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Methotrexate; Leflunomide; Hydroxychloroquine; Sulfasalazine
• Other Study ID Numbers: MSC12665; 2012-004339-21; U1111-1130-9931 (OTHER: UTN)