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] - Immune System Diseases [C20] |
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 |
The primary objective of this study is to evaluate the efficacy of 2 oral dosing regimens of fostamatinib (Regimen A - 100 mg twice daily (bid); Regimen B - induction with 100 mg bid for the first 4 weeks, 150 mg once daily (qd) maintenance thereafter) taken in combination with a disease-modifying anti-rheumatic drug (DMARD), compared with placebo plus a DMARD, in patients with active rheumatoid arthritis (RA). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study assessed over the 52-week study period are:
• To assess the efficacy of fostamatinib in the prevention of structural joint damage, as measured by change in radiographic modified Total Sharp Score (mTSS) and the components of mTSS at Week 24 and Week 52.
• To further assess the efficacy of fostamatinib measured by ACR20, ACR 50% response criteria (ACR50), ACR 70% response criteria (ACR70), major clinical response, ACR-N and the individual components of the ACR score.
• To assess physical function status of patients after administration of fostamatinib using the Health Assessment Questionnaire - Disability Index (HAQ-DI).
• To evaluate the efficacy of fostamatinib as measured by Disease Activity Score based on a 28 joint count (DAS28) and DAS28 European League Against Rheumatism (EULAR) response criteria.
• To investigate the effects of fostamatinib on patient reported health outcomes measures. |
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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 |
Pharmacogenetics and Exploratory Genetic and Biomarker Research
(Appendix D to clinical study protocol), 18th June, 2010.
Objectives:
To collect and store DNA for future exploratory research into
genes/genetic variation that may influence response (ie, absorption,
distribution, metabolism and excretion, safety, tolerability and efficacy)
to fostamatinib and/or DMARDs; and/or susceptibility to, progression of
and prognosis of RA; and/or associated biomarkers.
To investigate systemic biomarker profiles in RA patients. |
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E.3 | Principal inclusion criteria |
1. Male or female aged 18 and over
2. A diagnosis of RA after the age of 16
3. Currently taking 1 of the following traditional DMARDs: methotrexate, sulfasalazine, hydroxychloroquine or chloroquine. |
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E.4 | Principal exclusion criteria |
1. Females who are pregnant/lactating
2. Any systemic inflammatory conditions(other than RA), connective tissue disease or chronic pain disorders that may interfere with the interpretation of the outcome data
3. Poorly controlled blood pressure
4. History of liver function abnormality requiring investigation, drug induced liver injury, chronic liver disease, excessive alcohol consumption/chronic alcohol induced disease |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in this study is the proportion of patients achieving
ACR20 at Week 24. |
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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) |
− mTSS, radiographic erosion score (ES) and joint space narrowing
(JSN).
− ACR20, ACR50, ACR70, major clinical response, ACR-N, individual
components of ACR (swollen joint count, tender joint count, patient's
assessment of pain, patient's global assessment of disease activity,
physician's global assessment of disease activity, patient's assessment
of physical function, as measured by the HAQ-DI, C-reactive protein
[CRP] or erythrocyte sedimentation rate [ESR])
− HAQ-DI score; HAQ-DI response, individual dimensions of HAQ-DI
− DAS28 response, DAS28 EULAR response criteria, DAS low disease
activity, DAS28 remission, clinically important change in DAS28 score. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary timepoints are: Screening plus week 0-6, 12, 24, 28, 36 and
52.
For mTSS JSN (X-ray) timepoints 0, 12, 24 and 52
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 61 |
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 |
Canada |
Czech Republic |
Germany |
India |
Israel |
Italy |
Latvia |
Lithuania |
Portugal |
Romania |
Serbia |
South Africa |
Spain |
Ukraine |
United Kingdom |
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 | 1 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |