E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Active Ankylosing Spondylitis |
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MedDRA Classification |
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 evaluate adalimumab 40 mg eow sc in subjects with active AS in day-to-day clinical practice. The safety and efficacy of adalimumab will be analyzed based on concomitant NSAID use, concomitant steroid use, concomitant DMARD use, and prior exposure to other TNF inhibitors (etanercept, infliximab). The safety and efficacy of adalimumab in subjects with AS will be evaluated based on the type of clinical presentation of the disease (axial, peripheral arthritis, and /or enthesitis). The number of subjects with total ankylosis of the spine was limited in previous phase 3 studies of adalimumab in AS, thus, limited experience is available for use of adalimumab in subjects with advanced, including total ankylosis of the spine. This study will allow for further analyses of safety and efficacy in subjects with advanced spinal ankylosis. The safety and efficacy profile will also be evaluated by AS associated disorders including inflammatory bowel disease, psoriasis and uveitis. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
A subject will be eligible for study participation if he/she meets all of the following criteria: 1. Able and willing to give written informed consent and to comply with the requirements of the study protocol. 2. Males and females 18 years of age or older. 3. Diagnosis of AS according to the modified New York Criteria for Ankylosing Spondylitis 1984. 4. Documented active AS based on the opinion of a physician for at least 3 months. 5. Active AS with BASDAI ≥ 4 at the Screening Visit. 6. Unsatisfactory response to standard AS therapies in accordance with the current national guidelines for treatment of AS with TNF inhibitors (if applicable) including a minimum of failing at least one NSAID. National guidelines (if applicable) must be followed if the guidelines are more strict regarding the use of TNF inhibitors for the treatment of AS. 7. Use of reliable method of contraception, e.g., IUDs, condoms, or hormone (oral, implantable, or injectable) contraceptives by all female subjects of childbearing potential. Subject must follow the manufacture’s recommendations of contraception prior to the administration of study drug and through 150 days following the last administration of adalimumab. 8. Able and willing to self-administer sc injections or have available a suitable person to administer sc injections. 9. A negative pregnancy test (serum HCG) for women of childbearing potential prior to start of study treatment. 10. Subject must be evaluated for active and latent TB infection by using a PPD skin test, T SPOT-TB test, chest x-ray and a detailed review of the subject's medical history. Guidelines regarding the treatment of latent TB must be followed prior to the administration of adalimumab. |
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E.4 | Principal exclusion criteria |
A subject will be excluded from the study if he/she meets any of the following criteria: 1. Prior treatment with any investigational agent within 30 days, or five half-lives of the product, which ever is longer. 2. Treatment within the last two months with infliximab or within the last three weeks with etanercept or previous treatment at any time with adalimumab. 3. Known allergy to excipients of adalimumab formulation. 4. History of or current acute inflammatory joint disease of origin other than AS, e.g., rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus etc. 5. Treatment with corticosteroids (prednisolone equivalents) under the following conditions: ● Dose is >10 mg/d systemically within the 28 days before screening. ● Intraarticular injections or infiltrations of peripheral joints and tendons within 28 days before or at screening. ● Intraarticular injections of sacraliliac joints without therapeutic response <14 days before screening. 6. Other medical conditions: uncontrolled diabetes, unstable ischemic heart disease, congestive heart failure (NYHA III-IV), recent stroke (within three months), chronic leg ulcer and any other condition (e.g., indwelling urinary catheter) which, in the opinion of the investigator, would put the subject at risk by participation in the study. 7. History of cancer or malignant lymphoproliferative disease other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix. 8. History of positive serology for hepatitis B indicating active infection or history of positive serology for hepatitis C. 9. History of positive HIV status. 10. Persistent or recurrent infections or severe infections requiring hospitalization or treatment with iv antibiotics within 30 days, or oral antibiotics within 14 days prior to enrollment. 11. Previous diagnosis or signs highly indicative of central nervous system demyelinating diseases (e.g., optic neuritis, ataxia, apraxia). 12. History of active tuberculosis, histoplasmosis or listeriosis. 13. Female subjects who are pregnant or breast-feeding. 14. History of clinically significant drug or alcohol abuse in the last year. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
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.8.6 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 | Information not present in EudraCT |
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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The end-of-study is defined as the date of the last subject's last scheduled visit or the actual date of follow-up contact, whichever is longer.
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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 | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 11 |