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 | 14.1 |
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 |
Part A:
To demonstrate that SAR153191 (REGN88) on top of MTX is effective on reduction of signs and symptoms of rheumatoid arthritis at 12 weeks
Part B:
To demonstrate that sarilumab added to MTX is effective in:
- reduction of signs and symptoms of rheumatoid arthritis at 24 weeks
- inhibition of progression of structural damage at 52 weeks
- improvement in physical function at 16 weeks |
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E.2.2 | Secondary objectives of the trial |
To demonstrate that sarilumab added to MTX is effective in induction of a major clinical response at 52 weeks
To assess the safety of sarilumab added to MTX
To document the pharmacokinetic profile of sarilumab added to MTX, in patients with active rheumatoid arthritis who are inadequate responders to MTX therapy. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
To collect DNA, RNA and other biomarkers for future use for the purpose of discovery of predictive biomarkers.
Version 1
19 October 2009 |
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E.3 | Principal inclusion criteria |
Diagnosis of rheumatoid arthritis ≥ 3 months duration,
Active disease defined as:
- at least 8/68 tender joints and 6/66 swollen joints,
- high sensitivity C-reactive protein (hs-CRP) > 6 mg/l,
- continuous treatment with MTX for at least 12 weeks prior to baseline visit and on stable dose for 6
weeks prior to screening visit.
Part B only:
- Bone erosion based on documented X-ray prior to first study drug intake, or
- Cyclic Citrullinated Peptide (CCP) positive, or
- Rheumatoid Factor (RF) positive. |
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E.4 | Principal exclusion criteria |
Age <18 years or >75 years
Treatment with disease-modifying antirheumatic drugs (DMARDs) other than MTX within 4 weeks or 12 weeks prior to screening (depending on DMARDs).
Past history of non response to prior Tumor Necrosis Factor (TNF) or biologic treatment.
Any past or current biologic agents for the treatment of rheumatoid arthritis within 3 months.
Use of parenteral glucocorticoids or intraarticular glucocorticoids within 4 weeks prior to screening
visit.
Use of oral glucocorticoid greater than 10mg/day or equivalent/day, or a change in dosage within 4 weeks prior to baseline visit. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part A:
Percentage of patients who achieved American College of Rheumatology criteria for improvement ACR20
Part B:
- ACR20 response at Week 24
- Change in modified Van der Heijde total Sharp score at Week 52
- Change in physical function as measured by the change from baseline in the Health Assessment Question-Disability (HAQ-DI) at Week 16 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Part A: at week 12
Part B: at week 24 and week 52 |
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E.5.2 | Secondary end point(s) |
Part B: Major clinical response defined as the event of achieving and maintaining an ACR 70 response (for at least 24 weeks).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 52 for all above mentioned secondary endpoints |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 6 |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 74 |
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 | Information not present in EudraCT |
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 |
Argentina |
Australia |
Belarus |
Brazil |
Canada |
Chile |
Colombia |
Egypt |
India |
Korea, Republic of |
Malaysia |
New Zealand |
Thailand |
Mexico |
Philippines |
Russian Federation |
South Africa |
Taiwan |
Turkey |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 43 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 43 |