E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in disease activity score 28 (DAS28) - erythrocyte sedimentation rate (ESR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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 |
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 48 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Chile |
Czech Republic |
Germany |
Hungary |
Israel |
Korea, Republic of |
Peru |
Poland |
Puerto Rico |
Romania |
Russian Federation |
South Africa |
Spain |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Total study duration is up to 310 weeks: up to a 4 week screening
period, 24 week randomized treatment phase, up to maximum 276
week open label exension, and 6 weeks post-treatment final study visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |