E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Male and female patients over 18 years of age, with active RA despite current treatment with methotrexate. All patients will continue with background methotrexate therapy. |
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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 |
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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 effect of AZD5672 (20, 50, 100 and 150 mg once daily) on the signs and symptoms of rheumatoid arthritis (RA) in patients on background methotrexate therapy, |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: To further evaluate the effect of AZD5672 on the signs and symptoms of rheumatoid arthritis in patients on background methotrexate therapy as measured by: − ACR20 response at 4 and 8 weeks − ACR50, ACR70 and Hybrid ACR response (4, 8, and 12 weeks) − Individual components of the ACR response criteria (4, 8, and 12 weeks) − Erythrocyte Sedimentation Rate (4, 8, and 12 weeks) − DAS28 scores and response rates (4, 8, and 12 weeks). To evaluate the safety and tolerability of AZD5672 in patients on background methotrexate therapy |
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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 |
FARMACOGENETICA: Versione:1 Data:2008/03/14 Titolo:GENETICS RESEARCH Obiettivi:Testare l'effetto del genotipo del CCR5 sulleffetto del trattamento con AZD5672. - Ottenere dei campioni di DNA per consentire lindagine sui fattori genetici che potrebbero influire sullassorbimento, la distribuzione, il metabolismo e lescrezione, sullefficacia, la sicurezza e la tollerabilita' di AZD5672, metotrexato ed etanercept e sulla progressione e la prognosi dellAR nella popolazione di studio.
FARMACOCINETICA/FARMACODINAMICA: Versione:1 Data:2008/03/14 Titolo:Sottostudio di farmacococinetica Obiettivi:Misurare la quantita' di farmaco AZD5672) nel sangue.
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E.3 | Principal inclusion criteria |
Provision of informed consent (including PK subset consent, as applicable). 2. Male or female aged 18 or over. Note: Women of child-bearing potential may be included only if highly effective contraception is in place (see Section 3.3.4 and Appendix K) and patients are fully aware of the information relating to the potential for reprotoxicity as detailed in the informed consent form. 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. 3. Diagnosis of RA after the age of 16 according to the revised (1987) criteria of the American College of Rheumatology (see Appendix E).4. Have active RA defined as: − ≥4 swollen joints and ≥6 tender/painful joints (from 28 joint count, see Section 4.6.1.1) and either: ESR ≥28 mm/h or, CRP ≥10 mg/L. 5. At least one of the following: − Documented history of positive rheumatoid factor − Current presence of rheumatoid factor − Baseline radiographic erosion − Presence of serum anti-cyclic citrullinated peptide antibodies (anti-CCP). 6. Oral or subcutaneous or intramuscular methotrexate for at least 6 months prior to randomisation. The dose and means of administering methotrexate must have been stable between 5 mg and 25 mg per week for at least 6 weeks prior to randomisation. For inclusion in the genetic research, patients must fulfil the following criterion: 1. Provision of informed consent for genetic research If a patient declines to participate in the genetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this clinical study protocol, so long as they consent. |
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E.4 | Principal exclusion criteria |
1. Pregnant or lactating females (restrictions and procedures concerned with managing the risk of pregnancy/conception for males and females are provided in Section 3.3.4 and 9.4). 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 (see Appendix F) or wheelchair/bed-bound. 5. Patient unable to comply with the local approved product information for etanercept. Note: any patients randomised to receive etanercept will be confirmed as negative for LTBI prior to initiation of treatment. If the patient has had a negative TB test in the month prior to Visit 1, the result of that test will stand and the test does not need to be repeated. Patients who have a positive test result should be discontinued, see Section 3.3.5.1). Note: Where a local label is not available, then the label applicable to the supplied drug will apply. 6. Patients who have previously failed to respond to treatment with more than 1 biological agent. 7. Patients who in the opinion of the investigator have active TB as defined by clinical history and/or chest X-ray. 8. Patients who fail to comply with or are unlikely to stay compliant with the restrictions on prior and concomitant medication usage as provided in Section 3.7. 9. Clinical or biochemical evidence of active infection with hepatitis B or hepatitis C (carriers ie, those with positive serology but no evidence of active disease may be included). 10. Values of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or bilirubin >2 x upper limit of normal (ULN) at Visit 1. Note: If a potential patient has liver function only marginally outside these limits (as judged by the investigator), the patient may at the investigators discretion be brought back to study centre and retested not less than 2 weeks later and may be enrolled in the trial if the test(s) is then within the prescribed limit. 11. History of excessive alcohol consumption or chronic alcohol induced disease. See the protocol on p. 32-33 |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary effucacy variable of this trial is the proportion of patients who achieve ab ACR20 response at week 12. |
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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 | 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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
- same IMP used at different dosage |
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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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
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 |
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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 | |
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 | 0 |