Efficacy and Safety of Sarilumab and Adalimumab Monotherapy in Patients With Rheumatoid Arthritis (SARIL-RA-MONARCH)

NCT02332590 | Completed Phase 3 Results DMC

• 3 other identifiers: EFC140922014-002541-22U1111-1160-6154
• Study Type: interventional
• Target: 369
• Locations: 15 countries
• Sites: 86

Brief Summary

Primary Objective: To demonstrate that sarilumab monotherapy was superior to adalimumab monotherapy with respect to signs and symptoms as assessed by disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) in participants with active rheumatoid arthritis (RA) who were either intolerant of, or considered inappropriate candidates for continued treatment with methotrexate (MTX), or after at least 12 weeks of continued treatment with MTX, were determined to be inadequate responders. Secondary Objectives: To demonstrate that sarilumab monotherapy was superior to adalimumab monotherapy in participants with active RA who were either intolerant of, or considered inappropriate candidates for continued treatment with MTX, or after at least 12 weeks of continued treatment with MTX, were determined to be inadequate responders, with respect to:

• Reduction of signs and symptoms of RA.
• Improvement in quality of life assessed by participant reported outcome questionnaires. Assessment of the safety and tolerability of sarilumab monotherapy (including immunogenicity) throughout the study.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• DB Period: Change From Baseline in Disease Activity Score for 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 24

  DAS28-ESR is a composite score that includes 4 variables: TJC (based on 28 joints); SJC (based on 28 joints); GH assessment by the participant assessed from the ACR and RA core set questionnaire (participant global assessment) in 100 mm VAS; Marker of inflammation assessed by ESR in mm/hr. The DAS28-ESR score provides a number indicating the current disease activity of the RA. DAS28-ESR total score ranges from 2-10. A DAS28-ESR score above 5.1 means high disease activity, DAS28-ESR score below 3.2 indicates low disease activity and DAS28-ESR score below 2.6 means disease remission. Least square (LS) mean and standard error (SE) at Week 24 were obtained using Mixed-effect model with repeated measures (MMRM) approach.

  Baseline, Week 24

Secondary Outcomes (52)

• DB Period: Percentage of Participants Achieving Clinical Remission Score (DAS28-ESR <2.6) at Week 24

  Week 24

• DB Period: Percentage of Participants Achieving ACR50 Criteria at Week 24

  Week 24

• DB Period: Percentage of Participants Achieving ACR70 Criteria at Week 24

  Week 24

• DB Period: Percentage of Participants Achieving ACR20 Criteria at Week 24

  Week 24

• DB Period: Change From Baseline in HAQ-DI at Week 24

  Baseline, Week 24

Study Arms (2)

Adalimumab 40 mg/Sarilumab 200 mg

ACTIVE COMPARATOR

Adalimumab 40 milligrams (mg) subcutaneous (SC) injection in combination with placebo for sarilumab every 2 weeks (q2w) for 24 weeks during the double-blind (DB) period. The dosing frequency of adalimumab was adjusted to 40 mg every week (qw) dosing in case of participants with inadequate response (less than \[\<\] 20% improvement from baseline in tender joint count \[TJC\] and swollen joint count \[SJC\] for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in open label extension (OLE) period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).

Drug: Adalimumab; Drug: Placebo (for sarilumab)

Sarilumab 200 mg/Sarilumab 200 mg

EXPERIMENTAL

Sarilumab 200 mg SC injection in combination with placebo for adalimumab q2w for 24 weeks during the DB period. The dosing frequency of placebo for adalimumab was adjusted to 40 mg qw dosing in case of participants with inadequate response (\<20% improvement from baseline in TJC and SJC for 2 consecutive visits) at or after Week 16 until Week 23. Participants who completed 24 weeks in the DB period had the option to continue in OLE period and received sarilumab 200 mg q2w until commercial availability of sarilumab in their country or up to a maximum of an additional 276 weeks (i.e. up to Week 300).

Drug: Sarilumab; Drug: Placebo (for adalimumab)

Interventions

Sarilumab DRUG

Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: SC

Also known as: SAR153191, REGN88

Sarilumab 200 mg/Sarilumab 200 mg

Adalimumab DRUG

Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: SC

Also known as: Humira

Adalimumab 40 mg/Sarilumab 200 mg

Placebo (for sarilumab) DRUG

Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: SC

Adalimumab 40 mg/Sarilumab 200 mg

Placebo (for adalimumab) DRUG

Pharmaceutical form: solution for injection in pre-filled syringe; Route of administration: SC

Sarilumab 200 mg/Sarilumab 200 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of RA greater than or equal to (\>=)3 months duration.
• American College of Rheumatology (ACR) Class I-III functional status.
• Active RA was 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 millimeter per hour (mm/H), and DAS28-ESR greater than (\>) 5.1.
• Participants as per Investigator judgment were either intolerant of, or considered inappropriate candidates for continued treatment with MTX, or after at least 12 weeks of continued treatment with MTX, or inadequate responders treated with an adequate MTX dose for at least 12 weeks.

You may not qualify if:

• Age \<18 years or the legal age of consent in the country of the study site, whichever was higher.
• Current treatment with disease-modifying antirheumatic drug (DMARDs)/immunosuppressive agents including MTX, cyclosporine, mycophenolate, tacrolimus, gold, penicillamine, sulfasalazine or hydroxychloroquine within 2 weeks prior to the baseline (Randomization Visit) or azathioprine, cyclophosphamide within 12 weeks prior to baseline (Randomization Visit) or leflunomide within 8 weeks prior to the Randomization Visit, or 4 weeks after cholestyramine washout.
• Treatment with any prior biologic agent, including anti-interleukin 6 (IL-6), IL-6 receptor (IL-6R) antagonists, and prior treatment with a Janus kinase inhibitor.
• Use of parenteral corticosteroids or intra-articular corticosteroids within 4 weeks prior to screening.
• The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (86)

Investigational Site Number 840407

Covina, California, 91723, United States

Location

Investigational Site Number 840400

Long Beach, California, 90808, United States

Location

Investigational Site Number 840141

Whittier, California, 90606, United States

Location

Investigational Site Number 840130

Lewes, Delaware, 19958, United States

Location

Investigational Site Number 840229

Coral Gables, Florida, 33134, United States

Location

Investigational Site Number 840128

Ormond Beach, Florida, 32174, United States

Location

Investigational Site Number 840403

St. Petersburg, Florida, 33708, United States

Location

Investigational Site Number 840140

Tampa, Florida, 33614, United States

Location

Investigational Site Number 840073

Cumberland, Maryland, 21502, United States

Location

Investigational Site Number 840202

Hagerstown, Maryland, 21740, United States

Location

Investigational Site Number 840232

Flint, Michigan, 48504, United States

Location

Investigational Site Number 840112

Lincoln, Nebraska, 68516, United States

Location

Investigational Site Number 840402

Charlotte, North Carolina, 28210, United States

Location

Investigational Site Number 840406

Hickory, North Carolina, 28601, United States

Location

Investigational Site Number 840404

Middleburg Heights, Ohio, 44130, United States

Location

Investigational Site Number 840127

Oklahoma City, Oklahoma, 73103, United States

Location

Investigational Site Number 840074

Mesquite, Texas, 75150, United States

Location

Investigational Site Number 152005

Osorno, 5311092, Chile

Location

Investigational Site Number 152001

Puerto Varas, Chile

Location

Investigational Site Number 152002

Santiago, 7501126, Chile

Location

Investigational Site Number 152050

Santiago, 8207257, Chile

Location

Investigational Site Number 152014

Talca, Chile

Location

Investigational Site Number 152015

Temuco IX Region, 4790928, Chile

Location

Investigational Site Number 152007

Viña del Mar, Chile

Location

Investigational Site Number 203001

Prague, 12850, Czechia

Location

Investigational Site Number 203033

Prague, 14800, Czechia

Location

Investigational Site Number 203030

Prague, Czechia

Location

Investigational Site Number 203002

Uherské Hradiště, 686 01, Czechia

Location

Investigational Site Number 276058

Cologne, 50937, Germany

Location

Investigational Site Number 276021

Osnabrück, 49074, Germany

Location

Investigational Site Number 348025

Budapest, 1027, Hungary

Location

Investigational Site Number 348020

Budapest, 1033, Hungary

Location

Investigational Site Number 348022

Budapest, 1036, Hungary

Location

Investigational Site Number 348024

Szombathely, 9700, Hungary

Location

Investigational Site Number 348023

Veszprém, 8200, Hungary

Location

Investigational Site Number 376032

Ashkelon, 78278, Israel

Location

Investigational Site Number 376031

Haifa, 34362, Israel

Location

Investigational Site Number 376030

Ramat Gan, 52621, Israel

Location

Investigational Site Number 376011

Tel Aviv, 64239, Israel

Location

Investigational Site Number 604003

Lima, LIMA 27, Peru

Location

Investigational Site Number 604005

Lima, LIMA 41, Peru

Location

Investigational Site Number 604022

Lima, Lima29, Peru

Location

Investigational Site Number 616056

Bytom, 41-902, Poland

Location

Investigational Site Number 616015

Elblag, Poland

Location

Investigational Site Number 616005

Lublin, 20-582, Poland

Location

Investigational Site Number 616030

Lublin, 20-954, Poland

Location

Investigational Site Number 616055

Nadarzyn, 05-830, Poland

Location

Investigational Site Number 616018

Poznan, 61-397, Poland

Location

Investigational Site Number 616016

Szczecin, 71-252, Poland

Location

Investigational Site Number 616004

Warsaw, 02-118, Poland

Location

Investigational Site Number 616031

Warsaw, 03-291, Poland

Location

Investigational Site Number 642006

Brăila, 810019, Romania

Location

Investigational Site Number 642001

Bucharest, 010976, Romania

Location

Investigational Site Number 642010

Bucharest, 011172, Romania

Location

Investigational Site Number 642002

Bucharest, 020983, Romania

Location

Investigational Site Number 642005

Galati, 800578, Romania

Location

Investigational Site Number 643006

Kemerovo, 650000, Russia

Location

Investigational Site Number 643020

Moscow, 115404, Russia

Location

Investigational Site Number 643001

Moscow, 115522, Russia

Location

Investigational Site Number 643031

Moscow, 121374, Russia

Location

Investigational Site Number 643030

Moscow, 125284, Russia

Location

Investigational Site Number 643008

Saint Petersburg, 192242, Russia

Location

Investigational Site Number 643011

Saratov, 410053, Russia

Location

Investigational Site Number 710011

Cape Town, 7405, South Africa

Location

Investigational Site Number 710007

Cape Town, 7500, South Africa

Location

Investigational Site Number 710004

Kempton Park, 1619, South Africa

Location

Investigational Site Number 410005

Daegu, 42601, South Korea

Location

Investigational Site Number 410004

Daejeon, 35233, South Korea

Location

Investigational Site Number 410006

Seoul, 01830, South Korea

Location

Investigational Site Number 410001

Seoul, 03080, South Korea

Location

Investigational Site Number 724003

Barakaldo, 48903, Spain

Location

Investigational Site Number 724015

Barcelona, 08034, Spain

Location

Investigational Site Number 724011

Barcelona / Sabadell, 08208, Spain

Location

Investigational Site Number 724001

Málaga, 29010, Spain

Location

Investigational Site Number 724012

Santiago de Compostela, 15705, Spain

Location

Investigational Site Number 724007

Seville, 41009, Spain

Location

Investigational Site Number 804029

Ivano-Frankivsk, 76018, Ukraine

Location

Investigational Site Number 804048

Kharkiv, 61058, Ukraine

Location

Investigational Site Number 804014

Kyiv, 01103, Ukraine

Location

Investigational Site Number 804047

Kyiv, 02125, Ukraine

Location

Investigational Site Number 804037

Lutsk, 43005, Ukraine

Location

Investigational Site Number 804046

Lviv, 79010, Ukraine

Location

Investigational Site Number 804049

Poltava, 36011, Ukraine

Location

Investigational Site Number 804011

Vinnitsya, 21018, Ukraine

Location

Investigational Site Number 804043

Vinnitsya, 21100, Ukraine

Location

Investigational Site Number 826001

Leytonstone, E11 1NR, United Kingdom

Location

Related Publications (12)

• Burmester GR, Strand V, Kivitz AJ, Hu CC, Wang S, van Hoogstraten H, Klier GL, Fleischmann R. Long-term safety and efficacy of sarilumab with or without background csDMARDs in rheumatoid arthritis. Rheumatology (Oxford). 2023 Oct 3;62(10):3268-3279. doi: 10.1093/rheumatology/kead062.

  PMID: 36727470 DERIVED

• Choy E, Bykerk V, Lee YC, van Hoogstraten H, Ford K, Praestgaard A, Perrot S, Pope J, Sebba A. Disproportionate articular pain is a frequent phenomenon in rheumatoid arthritis and responds to treatment with sarilumab. Rheumatology (Oxford). 2023 Jul 5;62(7):2386-2393. doi: 10.1093/rheumatology/keac659.

  PMID: 36413080 DERIVED

• Rubbert-Roth A, Furst DE, Fiore S, Praestgaard A, Bykerk V, Bingham CO, Charles-Schoeman C, Burmester G. Association between low hemoglobin, clinical measures, and patient-reported outcomes in patients with rheumatoid arthritis: results from post hoc analyses of three phase III trials of sarilumab. Arthritis Res Ther. 2022 Aug 25;24(1):207. doi: 10.1186/s13075-022-02891-x.

  PMID: 36008838 DERIVED

• Rehberg M, Giegerich C, Praestgaard A, van Hoogstraten H, Iglesias-Rodriguez M, Curtis JR, Gottenberg JE, Schwarting A, Castaneda S, Rubbert-Roth A, Choy EHS; MOBILITY, MONARCH, TARGET, and ASCERTAIN investigators. Identification of a Rule to Predict Response to Sarilumab in Patients with Rheumatoid Arthritis Using Machine Learning and Clinical Trial Data. Rheumatol Ther. 2021 Dec;8(4):1661-1675. doi: 10.1007/s40744-021-00361-5. Epub 2021 Sep 14.

  PMID: 34519964 DERIVED

• Strand V, Boklage SH, Kimura T, Joly F, Boyapati A, Msihid J. High levels of interleukin-6 in patients with rheumatoid arthritis are associated with greater improvements in health-related quality of life for sarilumab compared with adalimumab. Arthritis Res Ther. 2020 Oct 20;22(1):250. doi: 10.1186/s13075-020-02344-3.

  PMID: 33081825 DERIVED

• Genovese MC, Burmester GR, Hagino O, Thangavelu K, Iglesias-Rodriguez M, John GS, Gonzalez-Gay MA, Mandrup-Poulsen T, Fleischmann R. Interleukin-6 receptor blockade or TNFalpha inhibition for reducing glycaemia in patients with RA and diabetes: post hoc analyses of three randomised, controlled trials. Arthritis Res Ther. 2020 Sep 9;22(1):206. doi: 10.1186/s13075-020-02229-5.

  PMID: 32907617 DERIVED

• Genovese MC, Fleischmann R, Kivitz A, Lee EB, van Hoogstraten H, Kimura T, St John G, Mangan EK, Burmester GR. Efficacy and safety of sarilumab in combination with csDMARDs or as monotherapy in subpopulations of patients with moderately to severely active rheumatoid arthritis in three phase III randomized, controlled studies. Arthritis Res Ther. 2020 Jun 10;22(1):139. doi: 10.1186/s13075-020-02194-z.

  PMID: 32522251 DERIVED

• Boyapati A, Schwartzman S, Msihid J, Choy E, Genovese MC, Burmester GR, Lam G, Kimura T, Sadeh J, Weinreich DM, Yancopoulos GD, Graham NMH. Association of High Serum Interleukin-6 Levels With Severe Progression of Rheumatoid Arthritis and Increased Treatment Response Differentiating Sarilumab From Adalimumab or Methotrexate in a Post Hoc Analysis. Arthritis Rheumatol. 2020 Sep;72(9):1456-1466. doi: 10.1002/art.41299. Epub 2020 Aug 25.

  PMID: 32343882 DERIVED

• Gabay C, Burmester GR, Strand V, Msihid J, Zilberstein M, Kimura T, van Hoogstraten H, Boklage SH, Sadeh J, Graham NMH, Boyapati A. Sarilumab and adalimumab differential effects on bone remodelling and cardiovascular risk biomarkers, and predictions of treatment outcomes. Arthritis Res Ther. 2020 Apr 7;22(1):70. doi: 10.1186/s13075-020-02163-6.

  PMID: 32264972 DERIVED

• Burmester GR, Strand V, Rubbert-Roth A, Amital H, Raskina T, Gomez-Centeno A, Pena-Rossi C, Gervitz L, Thangavelu K, St John G, Boklage S, Genovese MC. Safety and efficacy of switching from adalimumab to sarilumab in patients with rheumatoid arthritis in the ongoing MONARCH open-label extension. RMD Open. 2019 Oct 18;5(2):e001017. doi: 10.1136/rmdopen-2019-001017. eCollection 2019.

  PMID: 31673415 DERIVED

• Gossec L, Strand V, Proudfoot C, Chen CI, Guillonneau S, Kimura T, van Hoogstraten H, Mangan E, Reaney M. Effects of Sarilumab on Rheumatoid Arthritis as Reported by Patients Using the Rheumatoid Arthritis Impact of Disease Scale. J Rheumatol. 2019 Oct;46(10):1259-1267. doi: 10.3899/jrheum.180904. Epub 2019 Mar 15.

  PMID: 30877216 DERIVED

• Burmester GR, Lin Y, Patel R, van Adelsberg J, Mangan EK, Graham NM, van Hoogstraten H, Bauer D, Ignacio Vargas J, Lee EB. Efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy for the treatment of patients with active rheumatoid arthritis (MONARCH): a randomised, double-blind, parallel-group phase III trial. Ann Rheum Dis. 2017 May;76(5):840-847. doi: 10.1136/annrheumdis-2016-210310. Epub 2016 Nov 17.

  PMID: 27856432 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

sarilumab; Adalimumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: During the OLE period of this study, all participants received sarilumab 200 mg or 150 mg q2w via prefilled syringe.

Study Record Dates

• First Submitted: January 5, 2015
• First Posted: January 7, 2015
• Study Start: January 28, 2015
• Primary Completion: January 20, 2016
• Study Completion: December 29, 2020
• Last Updated: March 28, 2022
• Results First Posted: July 25, 2017

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

KR (4); US (17); UA (9); GB (1); ES (6); IL (4); CL (7); DE (2); PE (3); HU (5); RO (5); CZ (4); PL (9); RU (7); ZA (3)