| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10039073 |
| E.1.2 | Term | Rheumatoid arthritis |
|
| 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 the study is to evaluate the dose response relationship across 4 doses of AZD9056 (50, 100, 200 and 400 mg) on signs and symptoms of rheumatoid arthritis (RA), as measured by the proportion of patients meeting the American College of Rheumatology 20% response criteria (ACR20) at 6 months. |
|
| E.2.2 | Secondary objectives of the trial |
(1) To evaluate the dose response relationship across 4 doses of AZD9056 on signs and symptoms and disease activity of RA
(2) To investigate AZD9056 population pharmacokinetics in plasma in patients with RA
(3) To evaluate the safety and tolerability of AZD9056
(4) To provide information on the effects of AZD9056 on the quality of life measured by Short-Form-36 (SF-36) and Rheumatoid Arthritis Quality of Life (RAQoL) Questionnaire
(5) To investigate radiological changes using standard X-ray (using the Sharp score as modified according to the method of van der Heijde).
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Provision of informed consent
2. Male or female, aged 18 years or over
3. Females must be using 2 forms of contraception for the duration of the study and 4 weeks after the last dose of study medication, unless they are surgically sterile or post-menopausal. Males who are involved in the study must agree to abstain from procreative sex during the study and for 12 weeks after the last dose of study medication
4. Diagnosis of RA after the age of 16 according to the revised (1987) criteria of the American College of Rheumatology
5. Have active RA defined as: ≥4 swollen joints and ≥6 tender/painful joints (from 28 joint count) and either:
- ESR ≥28 mm/h
- CRP ≥10 mg/L.
6. At least one of the following:
- Documented history of positive rheumatoid factor
- Current presence of rheumatoid factor
- Baseline radiographic erosion
- Presence of serum anti-CCP antibodies.
7. Be receiving one of the following treatments:
- Oral or subcutaneous methotrexate for at least 6 months prior to randomisation.
- Oral sulphasalazine for at least 16 weeks prior to randomisation.
8. Haemoglobin at Visit 1 either:
− within the normal range, or
− below the normal range but not less than 9 g/dl and only if normochromic and
normocytic with no clinical or laboratory signs of chronic blood loss.
9. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
≤1.2 x upper limit of normal (ULN) at Visit 1; bilirubin within normal range at
Visit 1. |
|
| E.4 | Principal exclusion criteria |
1. Pregnant or lactating females
2. Any systemic inflammatory condition in addition to RA that may interfere with the interpretation of the outcome data (examples include but are not limited to polymyalgia rheumatica, giant cell [including temporal] arteritis, reactive arthritis)
3. Current chronic pain disorders including fibromyalgia and chronic fatigue syndromes
4. American College of Rheumatology functional class IV or wheelchair/bed-bound
5. Persistently abnormal liver function enzymes defined as AST/ALT >2 x ULN on more than one occasion in the past 6 months; or any pattern of liver function test abnormality in the previous 6 months requiring specific investigation
6. Treatment with any of the following:
- Leflunomide, cyclosporine or hydroxychloroquine within 28 days of randomisation. Note: Any patient that has received leflunomide less than 3 months but more than 4 weeks before randomisation must have completed a cholestyramine washout prior to study entry
- Biological agents and anti-TNF agents within 56 days (with the exception of rituximab, which must not have been used within 12 months) of randomisation
- Gold within 12 months of randomisation.
7. Any prior treatment with etanercept
8. Patients for whom etanercept is inappropriate including:
- Hypersensitivity to the active substance or to any of the excipients
- Sepsis or risk of sepsis
- Patients with active infections (including chronic or localised infections)
- Patients being treated with anakinra.
Note: Physicians should exercise caution in patients with a history of recurring or chronic infections or with underlying conditions that may predispose patients to infections (such as advanced or poorly controlled diabetes).
- Patients who have received live vaccine in the 4 weeks prior to randomisation
- Patients who have a previous history of blood dyscrasias
- Patients with pre-existing or recent onset of CNS demyelinating disease, or to those who are considered to have an increased risk of developing demyelinating disease
- Patients who have congestive heart failure
- Patients with Wegener's Granulomatosis.
9. Patients with a history of active tuberculosis or who have a positive tuberculin skin test or chest X-ray findings suggestive of active or healed tuberculosis (other than calcified foci alone).
10. Intramuscular steroid injection or intra-articular steroid injection within 6 weeks of randomisation
11. Patients receiving any of the following:
- Lovastatin
- Doses of simvastatin and atorvastatin >20 mg per day
- Moderate to strong CYP3A4 inhibitors/substrates
12. Patients receiving digoxin or cisapride
13. Patients with known Human Immunodeficiency Virus (HIV) or belong to a high risk group for HIV infection
14. Evidence of serum hepatitis or presence of hepatitis B surface antigen or hepatitis C antibodies
15. History of malignancy or neoplastic disease, except successfully treated basal or squamous cell carcinoma of the skin
16. Chronic liver or renal disease
17. Patients with current active peptic ulceration or a history of peptic ulcer disease in the previous 5 years
18. 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, or may influence the results of the study, or the patient’s ability to participate in the study
19. History of retinopathy
20. Clinically significant ECG abnormality (including abnormal QT/QTc interval, eg QTc >450 mm/sec according to Bazett’s formula) suggestive of underlying cardiovascular disease, which in the opinion of the investigator should preclude participation in the study.
21. Recent participation in a clinical study involving an investigational compound within 5 half-lives of the investigational product or 3 months prior to randomisation (whichever is longer). Patients involved in non-drug methodology studies (either invasive or non-invasive) may be included without delay, at the discretion of the investigator
22. Major surgery or significant other trauma in the 3 months prior to randomisation or expected surgery within 9 months of randomisation
23. History of excessive alcohol consumption or chronic alcohol induced disease
24. Patients who in the opinion of the investigator should not participate in the study
25. Previous enrolment or randomisation of treatment in the present study
26. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study centre).
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy variable of this trial is the proportion of treated patients who achieve ACR20 at Visit 8.
The proportion of patients who achieved ACR20 will be computed at Visits 3 to 9. Visit 8 (computed on the full analysis set) will be regarded as the primary endpoint. |
|
| 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 | Yes |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
|
| 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 | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 40 |
| 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 | Information not present in EudraCT |
| 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 |
|
| 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
|
| The end of study is defined as the date of database lock, which is the timepoint after which no patient will be exposed to study related activities. This definition is used to ensure consistency with trials conducted outside the EU. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 15 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 15 |
Print
