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 | 15.0 |
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 assess the effect of fostamatinib (100 mg twice daily [bid] taken in combination with a disease-modifying anti-rheumatic drug [DMARD]), relative to placebo plus a DMARD, on mean 24-hour ambulatory systolic blood pressure (SBP) at Week 4, in patients with active rheumatoid arthritis (RA). |
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E.2.2 | Secondary objectives of the trial |
• To assess the effect of fostamatinib (100 mg bid taken in combination with a DMARD), relative to placebo plus a DMARD, on mean 24-hour ambulatory diastolic blood pressure (DBP) at Week 4, in patients with active RA.
• To describe the effect of fostamatinib on blood pressure (BP) throughout the day by comparing daytime, night-time, awake and sleeping SBP and DBP between fostamatinib and placebo groups by ambulatory blood pressure monitoring (ABPM).
• To describe the effects of fostamatinib on BP as determined by clinic and home BP measurements.
• To describe the BP effects following discontinuation of fostamatinib (persistence and/or reversibility of any effect), including subjects who stopped the treatment prematurely due to BP elevation above the predefined threshold and for other safety reasons.
• To evaluate the efficacy of fostamatinib as measured by Disease Activity Score based on a 28 joint count (DAS28).
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female patients aged 18 or over diagnosed with Rheumatoid Arthritis after the age of 16
2. Active Rheumatoid Arthritis
3. Currently taking one of the following DMARD treatments: methotrexate, sulfasalazine, hydroxychloroquine or chloroquine.
4. Patients with essential hypertension may be included provided that their BP is controlled (<140/90 mmHg) with anti-hypertensive medications being stable at least 4 weeks prior to randomisation.
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E.4 | Principal exclusion criteria |
1. Females who are pregnant or breast feeding
2. Certain inflammatory conditions (other than RA), connective tissue diseases or chronic pain disorders
3. History of liver problems that have required previous investigations
4. Evidence of TB infection
5. Conditions that preclude or render difficult the 24-hour ABPM technique.
6. Known secondary causes of hypertension.
7. Evidence of recent significant CV disease.
8. Severely impaired renal function.
9. Evidence of recent or active infection.
10. Absolute neutrophil count (ANC) <1500/mm3 or 1.5 x 109/L.
11. Any other clinically significant disease or disorder, which in the opinion of the investigator (by its nature or by being inadequately controlled) might put the patient at risk due to participation in the study
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change from baseline in 24-hour mean ambulatory SBP |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 4 weeks of treatment with fostamatinib or placebo |
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E.5.2 | Secondary end point(s) |
Mean change from baseline in 24-hour mean ambulatory DBP
Mean change from baseline in mean daytime (6am-10pm) SBP and DBP, night time (10pm-6am) SBP and DBP, awake and sleeping SBP and DBP
Mean change from baseline in morning pre-dose and evening post-dose home SBP and DBP
Mean change from completion/discontinuation to follow-up in clinical measurement of SBP and DBP;
DAS28-CRP, DAS28-ESR, DAS28 EULAR response criteria, HAQ-DI, individual components of DAS28, patient’s global assessment of disease activity, physician’s global assessment of disease activity and patient’s assessment of pain, CRP, ESR.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 4 weeks of treatment with fostamatinib or placebo |
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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) | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
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 |
Argentina |
Brazil |
Bulgaria |
Czech Republic |
Germany |
Mexico |
Peru |
Poland |
South Africa |
Ukraine |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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As per protocol. The end of the study is defined as "the last visit of the last subject undergoing the study". |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |