Enthesitis With Ultra Sonography Doppler in Spondyloarthropathies Treated With Infliximab (Study P04440)
Condition: Spondylitis, Ankylosing; SpA
MeSH terms: Spondylitis; Spondylarthritis; Spondylarthropathies; Spondylitis, Ankylosing
Intervention: PDUS; Infliximab
Intervention description: PDUS scored for each enthesitis every 2 weeks for 24 weeks.; 5 mg/kg
IV
Frequency : weeks 0,2,6
Intervention MeSH terms: Infliximab
Phase: Phase 4
Study type: Interventional
Primary purpose: Diagnostic
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Subjects will be given 3 infusions of infliximab according to the label at week 0, 2, and 6.
      Subjects will be followed for a maximum of 18 weeks or until relapse. This study will assess
      the ability of the Power Doppler Ultrasonography (PDUS) to be a reliable marker of enthesitis
      response and relapse in subjects treated with infliximab.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Demonstrate willingness to participate in study, adhere to dose and visit schedules,
             and comply with procedures by signing a written informed consent.

          -  Negative serum pregnancy test at Week 0.

          -  Men and women over 18 years of either sex and any race.

          -  Free of any clinically relevant disease other than SpA that would in the principal
             investigator's and/or sponsor's opinion, interfere with the conduct of study or its
             evaluations.

          -  Eligible for anti-tumor necrosis factor (TNF) treatment according to applicable local
             guidelines.

          -  Fulfill the following criteria: European Spondyloarthropathy Study group (ESSG)
             Classification Criteria, and/or Amor Criteria, and/or New York modified criteria.

          -  Disease duration of SpA >6 months.

          -  Incomplete response to non-steriodal anti-inflammatory drug (NSAID).

          -  Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >4 including item 2 (axial
             pain) >=3 on a scale from 0 to 10.

          -  At least 1 enthesitis assessed by PDUS.

          -  C-reactive protein (CRP) twice upper normal laboratory value or inflammatory signal on
             magnetic resonance imaging (MRI) of spine or sacroiliac joint within the last 3
             months.

          -  Practicing adequate contraception during the study and for 6 months after last
             infusion.

          -  Week 0 laboratory tests must meet protocol criteria.

        Exclusion Criteria:

          -  Is a female who is pregnant, or intends to become pregnant during the study (or within
             6 months after receiving the last infusion);

          -  Is a female who is nursing, or intends to be nursing during the study or within 6
             month after having received the last infusion;

          -  Has childbearing potential without contraception throughout the study and for 6 months
             after receiving the last infusion.

          -  Has not observed the designated washout periods for any of the prohibited medications
             outlined in the protocol;

          -  Has any clinically significant deviation from the appropriate reference range in the
             physical examination, Chest X-ray, that, in the investigator's judgment, may interfere
             with the study evaluation or affect subject safety;

          -  Is in a situation or condition that, in the opinion of the investigator, may interfere
             with optimal participation in the study.

          -  Is on the staff, affiliated with, or a family member of the staff personnel directly
             involved with this study;

          -  Is allergic to or has sensitivity to the study drug or its excipients;

          -  Has intolerance to or contraindication for infliximab.

          -  Has an history of allergy to murine products.

          -  Is uncooperative or has not signed the consent form.

          -  Cannot understand the protocol.

          -  Has participated in a study within 3 months prior to inclusion.

          -  Had treatment with unstable doses of analgesic drugs (paracetamol, phenylbutazone,
             morphine) steroid, NSAID, or immunosuppressive agent, including methotrexate, within 4
             weeks prior to inclusion.

          -  Had Intra articular steroid within 4 weeks prior to inclusion.

          -  Had Previous treatment with infliximab

          -  Had previous treatment with etanercept, adalimumab or any other TNF agent within 2
             last months.

          -  Had an history of, ongoing or recurrent medical condition as follows :

               -  Infectious disease, including but not limited to chronic renal infection, chronic
                  chest infection (e.g. bronchectasis), sinusitis, recurrent urinary tract
                  infection (recurrent pyelonephritis or chronic nonremeting cystitis) open,
                  draining or infected skin wound, or ulcer. Serious infection(s) (such as
                  hepatitis, pneumonia or pyelonephritis) within 3 months prior to inclusion.

               -  Malignancy within the previous 5 years with the exception of basal cell carcinoma
                  of the skin that has been treated with no evidence of recurrence.

               -  Active tuberculosis or previous history of non treated or insufficiently treated
                  tuberculosis.

          -  Patients with a positive intradermal tuberculosis test according to the local
             recommendation

          -  For the patients who could have been in contact with a person having tuberculosis, the
             inclusion will be possible under specific conditions depending of local
             recommendations issued in France, Denmark, Hungary, Italy, Spain.

               -  Herpes zoster (shingles) infection within 2 months prior to the first infusion

               -  Opportunistic infections, e.g. cytomegalovirus, Pneumocystis carinii pneumonia,
                  aspergillosis, histoplasmosis or atypical mycobacterium infection.

          -  Has any of the following clinical conditions:

               -  Severe, progressive or uncontrolled renal, hepatic, hematologic,
                  gastrointestinal, endocrine, pulmonary, cardiac, neurologic, psychiatic or
                  cerebral diseases

               -  Known to be infected with human immunodeficiency virus (HIV), hepatitis B or
                  hepatitis C

               -  Known lymphoproliferative disease, including lymphoma, or signs suggestive of
                  lymphoproliferative disease, such as lymphadenoma of unusual size and
                  localization or splenomegaly.

               -  Have received live (attenuated) vaccination during the last 30 days

               -  Have been treated with a monoclonal antibody or a fusion protein except
                  etanercept, adalimumab or any other anti TNF agent

          -  Leukopenia < 3,500/mm^3, Hemoglobin < 9g/dl, thrombopenia < 100,000/mm^3.

          -  Congestive heart failure (CHF) including medically controlled, asymptomatic CHF or
             unstable hemodynamic cardiac conditions.

          -  Scheduled surgical intervention at any time during the study.

          -  Multiple sclerosis or symptomatic demyelination of central nervous system.

          -  Subjects who have an history of drug abuse or alcoholism