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 |
Patients with Rheumatoid arthritis who are being treated with methotrexate and have not had sufficient improvement in symptoms. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
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 |
Primary Objectives:
To assess the efficacy of treatment with MRA versus placebo, in combination with methotrexate (MTX), with regard to the following three primary endpoints in patients with moderate to severe active rheumatoid arthritis (RA) who have had an
inadequate response to MTX:
Reduction in signs and symptoms over 6 months,
Prevention of structural joint damage over 12 months (with confirmation at 24 months), and
Improvement in physical function over 12 months (with confirmation at 24 months).
To assess the safety of MRA versus placebo, in combination with methotrexate (MTX), with regard to adverse events and laboratory assessments.
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives:
- To explore the pharmacokinetics, immunogenicity and pharmacodynamic parameters of MRA in this patient population
- To assess long-term safety and efficacy of MRA administration in the defined patient population |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- adult patients at least 18 years of age with moderate to severe active RA for at least 6 months
- inadequate response to a stable dose of MTX
-patients of reproductive potential must be using reliable methods of contraception |
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E.4 | Principal exclusion criteria |
- major surgery (including joint surgery) within eight weeks before entering study, or planned surgery within 6 months after entering study
-prior treatment failure with an anti-tumor necrosis factor agent
- women who are prgenant or breast-feeding |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary.
1. At Week 24 (6 months):
Proportion of patients with ACR20 response
2. At Week 52 (12 months):
(a) Change from baseline* in modified Sharp total radiographic score
(b) Change in physical function as measured by the area under the curve for the
change from baseline in the Health Assessment Questionnaire (HAQ) Disability
Index
3. At Week 104 (24 months):
(a) Change from baseline* in modified Sharp total radiographic score (confirmation of
week 52 result)
(b) Change in physical function as measured by the area under the curve for the
change from baseline in the Health Assessment Questionnaire (HAQ) Disability
Index
*assessment taken prior to receiving first dose of study medication is considered baseline |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. At week 24 (6 months)
2. At week 54 (12 months)
3. At week 104 (24 months)
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E.5.2 | Secondary end point(s) |
- percentage of patients with ACR20/50/70 responses (Time frame: Week 24, 52 & 104)
- percentage of patients with ACR70 maintained for 6 months (Time frame: Week 24, 52 & 104)
- mean changes in parameters of ACR core set (Time frame: Week 24, 52 & 104)
- AEs, laboratory parameters, vital signs. Time frame:Throughout study)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At week 24 (6 months)
2. At week 54 (12 months)
3. At week 104 (24 months)
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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 | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 82 |
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 |
Australia |
Brazil |
China |
Denmark |
Finland |
France |
Greece |
Italy |
Mexico |
Norway |
Poland |
South Africa |
Spain |
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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The end of trial will occur when the last participating patient completes the last scheduled visit of the extension period, or when the sponsor decided to discontinue the development program.
All patients, including those who withdraw or complete the study, must return for follow-up assessments 4, 8 and 12 weeks after last dose of study medication. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 7 |
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 |