Phase 3
Completed N=369
Efficacy and Safety of Sarilumab and Adalimumab Monotherapy in Patients With Rheumatoid Arthritis (SARIL-RA-MONARCH)
Source: ClinicalTrials.gov NCT02332590 ↗Enrolled (actual)
369
Serious AEs
11.3%
Results posted
Jul 2017
Primary outcomePrimary: DB Period: Change From Baseline in Disease Activity Score for 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 24 — -2.20; -3.28 units on a scale — p=<0.0001
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY DB Period: Change From Baseline in Disease Activity Score for 28 Joints - Erythrocyte Sedimentation Rate (DAS28-ESR) Score at Week 24 |
-2.20; -3.28 | <0.0001 sig |
| SECONDARY DB Period: Percentage of Participants Achieving Clinical Remission Score (DAS28-ESR <2.6) at Week 24 |
7.0; 26.6 | <0.0001 sig |
| SECONDARY DB Period: Percentage of Participants Achieving ACR50 Criteria at Week 24 |
29.7; 45.7 | 0.0017 sig |
| SECONDARY DB Period: Percentage of Participants Achieving ACR70 Criteria at Week 24 |
11.9; 23.4 | 0.0036 sig |
| SECONDARY DB Period: Percentage of Participants Achieving ACR20 Criteria at Week 24 |
58.4; 71.7 | 0.0074 sig |
| SECONDARY DB Period: Change From Baseline in HAQ-DI at Week 24 |
-0.43; -0.61 | 0.0037 sig |
| SECONDARY DB Period: Change From Baseline in Short-Form-36 (SF-36) - Physical Component Summary (PCS) Score at Week 24 |
6.09; 8.74 | 0.0006 sig |
| SECONDARY DB Period: Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 24 |
8.41; 10.18 | 0.0689 |
| SECONDARY DB Period: Change From Baseline in SF-36 - Mental Health Component Summary Score at Week 24 |
6.83; 7.86 | — |
| SECONDARY DB Period: Change From Baseline in Disease Activity Score for 28 Joints Based on C-Reactive Protein (DAS28-CRP Score) at Week 24 |
-1.97; -2.86 | — |
| SECONDARY DB Period: Percentage of Participants Achieving Clinical Remission Score (DAS28-CRP <2.6) at Week 24 |
13.5; 34.2 | — |
| SECONDARY DB Period: Percentage of Participants Achieving Low Disease Activity (DAS28-ESR < 3.2) at Week 24 |
14.1; 42.9 | — |
| SECONDARY DB Period: Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Remission (CDAI ≤2.8) at Week 24 |
2.7; 7.1 | — |
| SECONDARY DB Period: Change From Baseline in CDAI at Week 24 |
-25.20; -28.94 | — |
| SECONDARY DB Period: Change From Baseline in European Quality of Life-5 Dimension 3 Level (EQ-5D-3L) Scores at Week 24 |
0.26; 0.32; 19.94; 24.22 | — |
| SECONDARY DB Period: Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) at Week 24 |
-2.30; -3.08 | — |
| SECONDARY DB Period: Change From Baseline in Work Productivity Survey - Rheumatoid Arthritis (WPS-RA) at Week 24: Work Days Missed Due to Arthritis |
0.05; -0.28 | — |
| SECONDARY DB Period: Change From Baseline in WPS-RA at Week 24: Days With Work Productivity Reduced by ≥ 50% Due to Arthritis |
-3.50; -3.74 | — |
| SECONDARY DB Period: Change From Baseline in WPS-RA at Week 24: Arthritis Interference With Work Productivity |
-2.510; -2.919 | — |
| SECONDARY DB Period: Change From Baseline in WPS-RA at Week 24: House Work Days Missed Due to Arthritis |
-4.22; -5.49 | — |
| SECONDARY DB Period: Change From Baseline in WPS-RA at Week 24: Days With Household Work Productivity Reduced by >= 50% Due to Arthritis |
-4.87; -6.70 | — |
| SECONDARY DB Period: Change From Baseline in WPS-RA at Week 24: Days With Family/Social/Leisure Activities Missed Due to Arthritis |
-3.33; -4.14 | — |
| SECONDARY DB Period: Change From Baseline in WPS-RA at Week 24: Days With Outside Help Hired Due to Arthritis |
-2.57; -3.43 | — |
| SECONDARY DB Period: Change From Baseline in WPS-RA at Week 24: RA Interference With Household Work Productivity |
-2.605; -3.276 | — |
| SECONDARY DB Period: Change From Baseline in Morning Stiffness VAS at Week 24 |
-29.29; -35.08 | — |
| SECONDARY DB Period: Change From Baseline in Individual ACR Component - TJC and SJC at Week 24 |
-16.45; -18.23; -12.20; -13.44 | — |
| SECONDARY DB Period: Change From Baseline in Individual ACR Component - Physician Global VAS, Participant Global VAS and Pain VAS at Week 24 |
-37.80; -45.33; -24.82; -33.30; -27.41; -36.19 | — |
| SECONDARY DB Period: Change From Baseline in Individual ACR Component - CRP Level at Week 24 |
-2.91; -17.01 | — |
| SECONDARY DB Period: Change From Baseline in Individual ACR Component- ESR Level at Week 24 |
-12.74; -32.11 | — |
| SECONDARY DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
117; 118; 13; 9 | — |
| SECONDARY OLE Period: Number of Participants With Treatment-emergent Adverse Events and Serious Adverse Events |
135; 143; 31; 25 | — |
| SECONDARY DB Period: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) - Hematological Parameters |
12; 7; 0; 1; 5; 5 | — |
| SECONDARY OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Hematological Parameters |
8; 5; 3; 3; 13; 13 | — |
| SECONDARY DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Liver Function Tests |
22; 36; 17; 26; 3; 5 | — |
| SECONDARY OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Liver Function Tests |
41; 36; 31; 34; 11; 10 | — |
| SECONDARY DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Metabolic Parameters |
10; 8; 17; 12; 3; 3 | — |
| SECONDARY OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Metabolic Parameters |
5; 6; 20; 14; 2; 2 | — |
| SECONDARY DB Period: Number of Participants With Different Post-baseline Categories of High-density Lipoprotein (HDL) |
5; 7; 57; 45; 119; 132 | — |
| SECONDARY OLE Period: Number of Participants With Different Post-baseline Categories of High-density Lipoprotein |
7; 5; 52; 49; 94; 111 | — |
| SECONDARY DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Renal Function |
0; 3; 19; 23; 0; 1 | — |
| SECONDARY OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Renal Function |
2; 2; 63; 62; 5; 1 | — |
| SECONDARY DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Urinalysis |
0; 0; 0; 0 | — |
| SECONDARY OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Urinalysis |
0; 0; 0; 1 | — |
| SECONDARY DB Period: Number of Participants With Potentially Clinically Significant Abnormalities - Electrolytes |
1; 1; 0; 0; 3; 0 | — |
| SECONDARY OLE Period: Number of Participants With Potentially Clinically Significant Abnormalities - Electrolytes |
3; 0; 0; 0; 2; 2 | — |
| SECONDARY DB Period: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities |
4; 5; 0; 0; 0; 0 | — |
| SECONDARY OLE Period: Number of Participants With Potentially Clinically Significant Electrocardiogram Abnormalities |
10; 19; 0; 3; 1; 1 | — |
| SECONDARY DB Period: Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities |
4; 3; 4; 5; 1; 1 | — |
| SECONDARY OLE Period: Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities |
3; 9; 10; 11; 0; 0 | — |
| SECONDARY DB Period: Number of Participants With Treatment-emergent and Treatment-boosted Anti-drug Antibody (ADA) Response |
13; 0 | — |
| SECONDARY Number of Participants With Treatment-emergent and Treatment-boosted Anti-drug Antibody Response During Entire Treatment-emergent Adverse Event Period |
11; 11; 0; 0 | — |
| SECONDARY DB Period: Pharmacokinetics: Serum Trough (Pre-dose) Concentrations of Functional Sarilumab |
0.00; 5566.03; 11209.64; 21355.19; 23143.39; 25252.43 | — |
| SECONDARY OLE Period: Pharmacokinetics: Serum Trough (Pre-dose) Concentrations of Functional Sarilumab |
109.38; 24403.72; 18952.69; 26006.07; 21911.87; 25571.16 | — |
Eligibility Criteria
Inclusion criteria
- 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.
Exclusion criteria
- 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.
Data sourced from ClinicalTrials.gov (NCT02332590). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.