Efficacy and safety of Sarilumab and Adalimumab monotherapy in patients with Rheumatoid Arthritis

• Register: EUCTR
• Last refreshed on: 12 April 2021
• Main ID: EUCTR2014-002541-22-CZ
• Date of registration: 09/12/2014
• Prospective Registration: Yes
• Primary sponsor: sanofi-aventis recherche & développement
• Public title: Efficacy and safety of Sarilumab and Adalimumab monotherapy in patients with Rheumatoid Arthritis
• Scientific title: A randomized, double-blind, parallel-group study assessing the efficacy and safety of sarilumab monotherapy versus adalimumab monotherapy in patients with rheumatoid arthritis - SARIL-RA-MONARCH
• Date of first enrolment: 26/01/2015
• Target sample size: 540
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-002541-22
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Chile, Czech Republic, Germany, Hungary, Israel, Korea, Republic of, Peru, Poland, Puerto Rico, Romania, Russian Federation, South Africa, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: www.sanofi.cz
• Affiliation: sanofi-aventis, s.r.o.

• Name: www.sanofi.cz
• Affiliation: sanofi-aventis, s.r.o.

Key inclusion & exclusion criteria

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 430
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 110

Exclusion criteria:
Age <18 years or the legal age of consent in the country of the study site, whichever is 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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Rheumatoid Arthritis
MedDRA version: 18.1 Level: PT Classification code 10039073 Term: Rheumatoid arthritis System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

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

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: 150-

Primary Outcome(s)

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.

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.

Primary end point(s): Change from baseline in disease activity score 28 (DAS28) - erythrocyte sedimentation rate (ESR)

Timepoint(s) of evaluation of this end point: Week 24

Secondary Outcome(s)

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: hematology, clinical chemistry, and urinalysis
Clinically significant changes in ECG
Clinically significant changes in vital signs
Measurement of anti-drug antibody (ADA) levels

Timepoint(s) of evaluation of this end point: 1 to 8: week 24
9: over time, maximum to week 306
10: week 24
11: over time, maximum to week 306

Secondary ID(s)

2014-002541-22-DE

EFC14092

Source(s) of Monetary Support

sanofi-aventis recherche & développement

Ethics review

Status: Approved
Approval date: 14/01/2015
Contact: