|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|The diagnosis of Ankylosing Spondylitis (AS) requires radiographically proven sacroiliitis.Inflammation on MRI is a prognostic factor for the development of AS. The aim is the decrease of inflammation on MRI of the SI joint and/or spine by giving them, a short period, anti-TNF therapy. The study is designed as a randomized, double-blind, placebo-controlled trial. After inclusion patients are randomly assigned to the etanercept- or placebo-arm of the study in a 1:1 ratio during 16 weeks.
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|Decrease of inflammation on MRI.
|Secondary objectives of the trial
|Improvement of disease acitivty scores.
|Trial contains a sub-study
|Principal inclusion criteria
|Patients to be included must meet the following criteria.
- age between 18-45 years, both male and female;
- inflammatory back pain for at least 3 months, but less than two years
- presence of ³2 SpA-features or
- presence of ³1 SpA-feature with HLA-B27 positivity or two family members with definite AS (1e or 2e degree family-member);
- no definite sacroiliitis on the X-ray (sacroiliitis grade 1 is sustained);
- active inflammatory lesions on MRI of the sacroiliac-joint and/or vertebral column
- have the capacity to understand and sign an informed consent form, are capable of reading and understanding subject assessment forms, and are willing and able to adhere to the study visit schedule and other protocol requirements.
- The screening laboratory test results must meet the following criteria:
- hemoglobin for males ³9.0 g/dL (5.6 mmol/L) and females ³8.5 g/dL (5.3 mmol/L);
- serum transaminase levels must be within 3 times the upper limit of normal range for the laboratory;
serum creatinine £1.4 mg/dL (123.8 mmol/L).
- NSAIDs it must be on a stable dose for at least 2 weeks prior to the first administration of study agent. If they currently are not using NSAIDs, they must not have received NSAIDs for at least 2 weeks prior to the first administration of the study drug.
|Principal exclusion criteria
|- definite AS (modified New York criteria (9);
- previous treatment with TNF-blockers.
General medical exclusion criteria:
- Women who are pregnant, nursing, or planning pregnancy within 2 months after the last; infusion (this includes fathers who plan on fathering a child within 2 months after the last injection);
- Documented seropositive for human immunodeficiency virus (HIV);
- Documented positive for hepatitis B surface antigen or hepatitis C;
- History of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results;
- Known history of serious infections (e.g., herpes zoster, cytomegalovirus, pneumocystis carinii, aspergillosis, histoplasmosis, coccidioidomycosis or mycobacteria other than TB) within 6 months prior to screening;
- History of lymphoproliferative disease, including lymphoma or signs suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location (e.g., nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic area), or splenomegaly;
- Any current known malignancy or history of malignancy within the previous 5 years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence;
- Any current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease;
- History of known demyelinating diseases such as multiple sclerosis or optic neuritis;
- Being unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access;
- Use of any investigational drug within 30 days prior to screening or within 5 half-lives of the investigational agent, whichever is longer;
- Presence of a transplanted solid organ (excluding a corneal transplant);
- Having a concomitant diagnosis or history of congestive heart failure;
- Having a history of latent or active TBC prior to screening;
- Having signs or symptoms suggestive of active TBC upon medical history and/or physical examination;
- Having had a recent close contact with a person with active TBC. If there has been such contact, a patient will be referred to a physician specializing in TBC to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TBC prior to or simultaneously with the first administration of study agent.
- Having contraindications for making an MRI such as electronically, magnetically, and mechanically activated implants, cardiac pacemakers, ferromagnetic or electronically operated stapedial implants, hemostatic clips (CNS) or metallic splinters in the orbit.
Exclusions are in line with warnings and contra-indications in the SmPC.
|E.5 End points
|Primary end point(s)
|Primary study parameters/outcome of the study:
Inflammation at MRI SI-joint/spine, after 16 weeks and 6 months.
|E.6 and E.7 Scope of the trial
|Scope of the trial
| Information not present in EudraCT
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|The trial involves multiple Member States
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
| Information not present in EudraCT
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|16 weeks intervention and 3 years follow-up. Last observation carried forward.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days