Infliximab as First Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial - INFAST

• Conditions: Moderate-to-severe active axial spondyloarthritis; MedDRA version: 9.1Level: LLTClassification code 10058338Term: Spondylarthritis

• Registration Number: EUCTR2008-000982-51-AT
• Lead Sponsor: Schering-Plough Research Institute, a Division of Schering Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-03-18
• Last Update Posted: 25 September 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1. Subject must be willing to give written informed consent & be able to adhere to the dose & visit schedules
2. Subject must be 18 to 48 yrs of age, of either sex, & of any race
3. Subject must have a diagnosis of active axial spondyloarthritis, w/disease duration of =3 yrs, based on ALL of the following findings: chronic low back pain (for a duration of >3 months to =3 yrs, with onset before the age of 45), active inflammatory lesions of the sacroiliac joints shown on MRI. Active inflammatory lesions are defined as bone edema within or adjacent the sacroiliac joints, compatible w/active lesions seen in AS or axial spondyloarthritis as observed w/short inversion recovery (STIR). One or more of the following spondyloarthritis manifestations: Inflammatory back pain according to Calin Criteria or Rudwaleit et al, Uveitis, Arthritis, Dactylitis, Psoriasis, ?History of CD/ulcerative colitis, HLA-B27 positive, good response to NSAIDs, CRP levels elevated above upper limit of normal (local lab), positive family history for Spondyloarthritis, Enthesitis
4. Subject must have active disease at Screening & Baseline defined by both a total back pain evaluation of =40 mm on a VAS of 0 to 100 mm AND a BASDAI score of =40 mm
5. Subject must meet 1 of the following criteria: be NSAID-naïve, OR if subject has been treated with an NSAID before Screening, average dose during the last 2 wks must not have escalated to more than two-thirds of the maximal recommended dose, AND in addition a washout period of =3 days has occurred before Baseline
6. Subject who is on an NSAID at Screening (& goes through a =3-day washout period before Baseline) must have an increase in total back pain of =30% at Baseline visit compared to Screening visit as measured by the Total Back Pain VAS
7. Women of childbearing potential & all men must agree to use a medically accepted method of contraception prior to entering the study while receiving protocol-specified medication, & for 6 months after stopping the medication. Acceptable methods of contraception include condoms (male or female) with or without spermicide, diaphragm or cervical cap with spermicide, medically prescribed intrauterine device (IUD), oral or injectable hormonal contraceptive, & surgical sterilization (eg, hysterectomy, tubal ligation for women, and vasectomy for men).Women of non-childbearing potential do not have to use any contraceptive methods
8. Women of childbearing potential & men who are not currently sexually active must agree to use a medically acceptable method of contraception should they become sexually active while participating in the study & receiving protocol-specified medication or within 6 months after stopping the medication
9. Subject is considered eligible according to the following tuberculosis (TB) criteria:
has no history of latent or active TB within 3 months prior to Screening (according to local standards and laws), has no signs or symptoms suggestive of active TB upon medical history &/or physical examination during Screening, has had no recent close contact with a person with active TB OR, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation, & have active and latent TB ruled out (according to local standards and laws) prior to first administration of study medication. In the case of a positive TB-test (as per local standards and laws), a subject can participate in this trial only if the subject agrees to & is able t

Exclusion Criteria

1. Subject has history of esophageal, gastric, pyloric channel, duodenal ulceration or clinically relevant gastrointestinal bleeding w/in 5yrs prior to Screening or history of gastrointestinal bleeding/perforation, related to previous NSAIDs therapy
2. Subject has evidence of active inflammatory bowel disease (CD or UC)
3. Subject has clinical gastrointestinal malabsorption, regardless of etiology
4. Subject has uncontrolled hypertension as per the discretion of treating physician
5. Subject has history of coronary heart disease, myocardial infarction, stroke, transient ischemic attack, or diagnosis of congestive heart failure, even if the subject is medically controlled &/or asymptomatic
6. Subject has another chronic inflammatory articular disease or systemic autoimmune disease such as Systemic Lupus Erythematosus, Sjogren’s syndrome, active rheumatoid vasculitis, or chronic fatigue syndrome
7. Subject w/a history of chronic or recurrent infectious disease including but not limited to chronic renal infection, chronic chest infection (eg, bronchiectasis), recurrent urinary tract infection (recurrent pyelonephritis or chronic non-remitting cystitis), open, draining, infected skin wounds or ulcers, or a history of recurrent bacterial infections w/encapsulated organisms
8. Subject has/had an opportunistic infection (infection caused by an organism such as cytomegalovirus, Pneumocystis carinii, aspergillus, histoplasmosis, or mycobacteria other than TB, in a host whose resistance is lowered by another disease or drug[s]) w/in 6mnths prior to Screening
9. Subject has/had herpes zoster infection w/in 2mnths prior to Screening.
10. Subject is known to be infected w/human immunodeficiency virus (HIV), hepatitis B or C
11. Subject has primary or secondary immunodeficiency
12. Subject has known history of lymphoproliferative disease, including lymphoma, signs & symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size/location
13. Subject has any known malignancy or history of malignancy w/in the previous 5yrs (w/the exception of basal cell carcinoma of the skin that has been treated w/no evidence of recurrence for 1yr prior to Screening)
14. Subject has had previous treatment w/a TNF-alpha targeted therapy or another biological agent
15. Subject has been on leflunomide during the previous 8wks prior to Screening (or during the previous 4wks prior to Screening if subject has undergone standard cholestyramine or activated charcoal washout)
16. Subject has been on DMARDs, sulfasalazine, methotrexate, corticosteroid (oral, intra-articular, parenteral) during previous 4wks prior to Screening
17. Subject has history of or current signs &/or symptoms of severe, progressive, uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary (eg, pulmonary insufficiency), cardiac, neurological, cerebral, or psychiatric disease
18. Subject has history of demyelinating disease, symptoms suggestive of multiple sclerosis or optic neuritis
19. Subject has a transplanted organ (w/the exception of a corneal transplant >3mnths prior to Baseline)
20. Subject has neuropathy that can interfere w/quality of life &/or pain assessment
21. Subject has known intolerance (including allergic reactions) to murine, chimeric proteins or human/murine recombinant products
22. Subject for whom a known intolerance to or contraindication for infliximab exists, or for whom infliximab is not recommended
23. Subject is not

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified