E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Early rheumatoid arthritis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10039073 |
E.1.2 | Term | Rheumatoid arthritis |
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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 evaluate the efficacy of ACZ885 plus MTX by assessing the response to treatment (ACR50) as compared to MTX alone in early RA patients after 6, 14 and 26 weeks of treatment |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy of ACZ885 plus MTX by assessing the response to treatment (ACR20, 70 and 90) as compared to MTX alone in early RA patients after 6, 14 and 26 weeks of treatment ユ To establish a biomarker profile including genomics, cytomics and biochemical markers of bone and cartilage turn over to dissect responders (ACR20) versus non-responders to ACZ885 plus MTX treatment after 6, 14 and 26 weeks of treatment. ユ To establish a biomarker profile including genomics, cytomics and biochemical markers of bone and cartilage turn over to dissect high-responders (ACR50) versus non-responders to ACZ885 plus MTX treatment after 6, 14 and 26 weeks of treatment ユ To evaluate the efficacy of ACZ885 plus MTX by assessing the response to treatment using the Simplified Disease Activity Index (SDAI) and DAS28 scoring as compared to MTX alone in early RA patients after 6, 14 and 26 weeks of treatment. ユPLEASE SEE PROTOCOL |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male and post-menopausal or surgically sterilized female patients aged 18-75 years, having provided a written informed consent and passed screening examinations. 2. Women of child-bearing potential may participate if they have a negative serum pregnancy test at screening and prior to dosing, and are willing to practice double-barrier contraception during the study (from the date of screening) and for at least 3 months following the last dose. 3. Weight >= 45 kg, body mass index (BMI) <= 34. 4. Patient has a recent definite diagnosis of RA (less than 3 years since diagnosis), classified by ARA (American Rheumatism Association) 1987 revised criteria. 5. Candidate for methotrexate or biologic due to erosive arthritis, with no contraindications to such therapy, including: a. Negative tuberculin skin test reaction (PPD 5 TU) (< 5 mm induration) at 48 to 72 hours after administration at the screening visit or within 2 months prior to the screening visit, according to national guidelines. Patients who have a positive PPD skin test, but were previously treated with anti-tuberculosis drugs, or are known to have a negative chest X-ray (within the last year) can be included (see Appendix describing most recent CDC guidelines to manage risk of TB reactivation, to assure source documentation that patient is at low risk). b. Normal chest X-ray (within the last year) prior to possibility of receiving MTX (r/o lung fibrosis). 6. Functional status class I, II or III classified according to the ACR (American College of Rheumatology) 1991 revised criteria. 7. Patient presents active disease at screening and baseline evaluation (same evaluator), defined as at least 6 swollen and 6 painful tender joints of 28 joint count, hsCRP >= 1.0 mg/dL, and/or ESR > 28 mm/h. 8. Oral corticosteroids are permitted as long as patients are on a stable dose (up to 10 mg) for at least 4 weeks. |
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E.4 | Principal exclusion criteria |
1. Contraindication for MRI of wrist / MCP joints. 2. Patients with magnetizable metal parts/devices on and in the body. 3. Patients with an unstable active medical condition likely to impair evaluation of safety and biomarker results. 4. Previous treatment with biological therapy or MTX. 5. Previous treatment with other disease-modifying anti-rheumatic drugs (DMARDS) such as sulfasalazine, hydroxychloroquine within 4 weeks of screening 6. Intra-articular corticosteroids within 4 weeks prior to screening. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is response to treatment according to the ACR50 criteria at 26 weeks. Patients will be defined as treatment responders at a given post-randomization visit if they satisfy the ACR50 criteria for response to treatment. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Information not present in EudraCT |
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) | No |
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 | No |
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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |