A randomized, double-blind, parallel-group study assessing the efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis

INTERVENTION:

Product Name: Sarilumab Product Code: SAR153191 (REGN88) Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed

INN:

Sarilumab Current Sponsor code: SAR153191 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ Pharmaceutical form of the placebo: Solution for injection in pre‐filled syringe Route of administration of the placebo: Subcutaneous use Trade Name: Humira, 40 mg solution for injection in pre‐filled syringe Product Name: adalimumab Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed

INN:

ADALIMUMAB CAS Number: 331731‐18‐1 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 40‐ Pharmaceutical form of the placebo: Solution for injection in pre‐filled syringe Route of administration of the placebo: Subcutaneous use

CONDITION:

Rheumatoid Arthritis ; MedDRA version: 17.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 ‐ Musculoskeletal and connective tissue disorders Therapeutic area: Diseases [C] ‐ Musculoskeletal Diseases [C05]

PRIMARY OUTCOME:

Main Objective: To demonstrate that sarilumab monotherapy is superior to adalimumab monotherapy with respect to signs and symptoms as assessed by disease activity score 28 (DAS28)‐erythrocyte sedimentation rate (ESR) in patients with active rheumatoid arthritis (RA) who are either intolerant of, or considered inappropriate candidates for continued treatment with methotrexate (MTX), or after at least 12 weeks of continuous treatment with MTX, are determined to be inadequate responders. Primary end point(s): Change from baseline in disease activity score 28 (DAS28) ‐ erythrocyte sedimentation rate (ESR) Secondary Objective: To demonstrate that sarilumab monotherapy is superior to adalimumab monotherapy in patients with active RA who are either intolerant of, or considered inappropriate candidates for continued treatment with methotrexate (MTX), or after at least 12 weeks of continuous treatment with MTX, are determined to be inadequate responders, with respect to:; • Reduction of signs and symptoms of RA ; • Improvement in quality of life assessed by patient reported outcome questionnaires. ; Assessment of the safety and tolerability of sarilumab monotherapy (including immunogenicity) throughout the study. Timepoint(s) of evaluation of this end point: Week 24

SECONDARY OUTCOME:

Secondary end point(s): 1‐ American College of Rheumatology 20 (ACR2020, ACR50 and ACR70 response ; 2‐ Change from baseline in each individual ACR component ; 3‐ Change from baseline in DAS28‐CRP ; 4‐ DAS28‐ESR remission (<2.6) ; 5‐ DAS28‐CRP remission (<2.6) ; 6‐ Low disease activity (DAS28‐ESR <3.2) ; 7‐ Remission based on clinical disease activity index (CDAI) (=2.8) ; 8‐ Change from baseline in CDAI ; 9‐ Sarilumab exposure assessed by trough serum sarilumab concentrations. ; 10‐ Change from baseline in: short form 36 (SF‐36) scores ; Change from baseline in: EQ‐5D‐3L scores ; Change from baseline in: rheumatoid arthritis impact of disease (RAID) scores ; Change from baseline in: work productivity survey‐rheumatoid arthritis (WPS‐RA) scores ; Change from baseline in: functional assessment of chronic illness therapy‐fatigue (FACIT‐F) scores ; Change from baseline in: morning stiffness visual analog scale (VAS) scores ; 11‐ Number of patients with adverse events ; Clinically significant changes in laboratory values, ECG and vital signs ; Measurement of anti‐drug antibody (ADA) levels ; Timepoint(s) of evaluation of this end point: 1 to 8: week 24 ; 9: week 54 ; 10: week 24 ; 11: week 54

INCLUSION CRITERIA:

Diagnosis of rheumatoid arthritis =3 months duration. American College of Rheumatology (ACR) Class I‐III functional status. Active RA, defined as: ‐ At least 6 of 66 swollen joints and 8 of 68 tender joints, ‐ High sensitivity C‐reactive protein (hs‐CRP)=8 mg/L or ESR=28 mm/H, and ‐ DAS28ESR >5.1. Patients who per investigator judgment were either intolerant of, or considered inappropriate candidates for continued treatment with methotrexate (MTX), or after at least 12 weeks of continuous treatment with MTX, or inadequate responders treated with an adequate MTX dose for at least 12 weeks. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 230 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 110