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] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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 |
To assess the efficacy of AZD9567, 40 mg, compared to prednisolone 20 mg in patients with active rheumatoid arthritis in spite of stable treatment with conventional and/or s.c/i.v. biological DMARDs, by evaluating Change from baseline in 28 joint Disease Activity Score using CRP (DAS 28 - CRP) |
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E.2.2 | Secondary objectives of the trial |
1. To further assess the efficacy of AZD9567, 40 mg, versus prednisolone 20 mg in patients with active RA in spite of stable treatment with conventional and/or s.c/i.v. biological DMARDs, by evaluating
Proportion of subjects reaching ACR (American College of Rheumatology) 20, 50 and 70 responses
Change from baseline in Swollen Joint Count 66 (SJC 66)
Change from baseline in Tender Joint Count 68 (TJC 68)
Change from baseline in individual components of DAS28 and ACR response criteria
2. To evaluate the pharmacokinetic profile of AZD9567 in patients with active RA (E g but not limited to plasma AUC(0-24), AUC(0-last), Cmax and tmax)
3. To assess the safety and tolerability of AZD9567 in patients with active RA (Adverse events, vital signs, ECG and laboratory parameters (hematology, clinical chemistry and urine) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of informed consent prior to any study specific procedures
2. Male and female patients aged 18 through 80 years at screening
3. Established RA diagnosis according to the 2010 American College of Rheumatology (ACR)/EULAR classification or the 1987 criteria
4. Active RA (DAS28-CRP score ≥ 3.2) with at least 3 swollen joints and 3 tender joints using the DAS28 joint count
5. Patients must have be on stable dosing of conventional and/or s.c./i.v biological DMARDs for the last 8 weeks prior to Visit 1
6. CRP levels >5mg/L at screening if seronegative for RF and anti-CCP Ab, or >2mg/L if seropositive for either marker
7. BMI between 18 and 35 (inclusive)
8. Negative pregnancy test (serum) for female subjects of childbearing potential. |
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E.4 | Principal exclusion criteria |
1. History or current inflammatory rheumatic disease other than RA (secondary Sjogren’s syndrome excluded)
2. History or current clinically important disease which may either put the subject at risk because of participation in the study, or influence the results or the subject’s ability to participate in the study
3. Any clinical contraindications to treatment with steroids
4. Oral or parenteral steroids (beyond study medication) 8 weeks prior to study start and during the study. Stable use and dose of topical and inhaled steroids for longer than 4 w prior to randomization is acceptable
5. Use of any prohibited medication during the study or if the required washout time of such medication was not adhered to (for details see Section 7.7.1)
6. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs with a similar class to study drugs
7. Any concomitant medications that are known to be associated with Torsades de Pointes, for additional information see Section 7.7.1)
8. Any clinically significant ECG; vital signs or laboratory abnormalities identified at screening or prior to randomisation |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Change from baseline in 28 joint Disease Activity Score using CRP (DAS 28 - CRP) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 5, end of treatment, to baseline, Visit 2 |
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E.5.2 | Secondary end point(s) |
• Proportion of subjects reaching ACR (American College of Rheumatology) 20, 50 and 70 responses
• Change from baseline in Swollen Joint Count 66 (SJC 66)
• Change from baseline in Tender Joint Count 68 (TJC 68)
• Change from baseline in individual components of DAS28 and ACR response criteria (number of swollen and tender joints, patients assessments of global disease activity, pain, physician´s global assessment of disease activity, and CRP)
E g but not limited to plasma AUC(0-24), AUC(0-last), Cmax and tmax of both AZD9567 and prenisolone
Adverse events, vital signs, ECG and laboratory parameters (hematology, clinical chemistry and urine) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visit 5, end of treatment, to baseline, Visit 2 |
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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 | 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 | No |
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 | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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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 | 2 |