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 objectives of this study are:
• To evaluate the efficacy of 3 oral dosing regimens of fostamatinib disodium (FosD) compared with placebo when used as monotherapy in patients with active rheumatoid arthritis (RA) by assessment of: The signs and symptoms of RA, as measured by Disease Activity Score based on a 28 joint count (DAS28) at Week 6.
• To evaluate whether the efficacy of 3 oral dosing regimens of fostamatinib are non-inferior to that of adalimumab (Humira®) when used as monotherapy in patients with active RA by assessment of: The signs and symptoms of RA, as measured by DAS28 at Week 24.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are:
• To further assess the efficacy of fostamatinib measured by DAS28, DAS28 response criteria, American College of Rheumatology 20% response criteria (ACR20), ACR 50% response criteria (ACR50), ACR 70% response criteria (ACR70), 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 investigate the effects of fostamatinib on health-related quality of life using the 36-item Short Form Health Survey (SF-36) questionnaire. |
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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 |
(Sub-study to OSKIRA-4): A Phase 118, Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of the Efficacy and Safety of Fostamatinib Disodium Monotherapy Compared with Placebo or Adalimumab Monotherapy in Patients with Active Rheumatoid Arthritis: Magnetic Resonance Imaging Sub-Study.
D4300C0004 (sub-study), Edition 1, 21 March 2011
Sub-study Objectives
In addition to the objectives described in the main study protocol, the sub-study will have the following objectives for the comparison of fostamatinib with placebo at 6 weeks and with adalimumab at 24 weeks in patients with Rheumatoid Arthritis (RA) using Magnetic Resonance Imaging (MRI) techniques.
Primary objective:
• To assess the efficacy of fostamatinib in reducing joint synovial
disease activity as measured by:
- Change from baseline to Week 6 (versus placebo) in OMERACT
RAMRIS synovitis score. |
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E.3 | Principal inclusion criteria |
1) Provision of informed consent, prior to any study-specific procedures.
2) Male or female aged 18 and over.
3) Diagnosis of RA, after the age of 16 according to the revised (1987) criteria of the American College of Rheumatology and one of the following:
-diagnosis within 5 years prior to Visit 1 and inadequate response to treatment with a maximum of 2 of the following DMARD therapies: methotrexate, leflunomide, sulfasalazine, azathioprine, cyclosporine, gold, penacillamine, minocycline, mycophenolate, cyclophosphamide, tacrolimus or doxycycline
or
-diagnosis within 5 years prior to Visit 1 and intolerance to DMARD therapy
or
-diagnosis within 2 years prior to Visit 1 and no previous use of DMARDs.
4) Active RA defined as:
- ≥4 swollen joints and ≥4 tender/painful joints (from 28 joint count)
and either:
- ESR ≥28 mm/h, or
- CRP ≥10 mg/L
5) At least 2 of the following:
-Documented history or current presence of positive rheumatoid factor (RF)
-Radiographic erosion within 12 months prior to enrolment
-Presence of serum anti-cyclic citrullinated peptide antibodies (anti CCP).
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E.4 | Principal exclusion criteria |
1) Use of any DMARDs within 6 weeks prior to Visit 1
2) Patients who have previously received treatment with a TNF alpha antagonist (including etanercept, certolizumab, adalimumab, infliximab, golimumab) or anakinra or previous treatment with other biological agent including rituximab, abatacept and tocilizumab
3) Females who are pregnant or lactating
4) Any systemic inflammatory conditions (other than RA), connective tissue disease or chronic pain disorders that may interfere with the interpretation of the outcome data.
5) Poorly controlled blood pressure
6) History of liver problems that have required previous investigation
7) Evidence of recent or significant CV disease, active or recent infection or evidence of tuberculosis infection |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints in this study are the signs and symptoms of RA, as measured by DAS28 at Week 6 and DAS28 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) |
Secondary outcome variables:
- DAS28 score, DAS28 response criteria, DAS low disease activity, DAS28 remission, clinically important change in DAS28 score
- ACR20, ACR50, ACR70, 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. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary timepoints are: Screening plus week 0 to 6, 12, 18 and 24. |
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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 | 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) | 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 | 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 | 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.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 |
Bulgaria |
Canada |
Czech Republic |
Germany |
Hungary |
Netherlands |
Poland |
Russian Federation |
Slovakia |
South Africa |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 9 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |