psoriatische artritis
Conditions
Interventions
The subjects will be treated with 3 mg/kg AIN457 every 4 weeks over a period of
24 weeks initially (Part 1), with a possible extension of a further 6 months
(Part 2).
Sponsors
Novartis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Patients who participate and complete the core CAIN457A2206 study up to and including the EoS i.e. Visit 16 (Week 24), may enter the extension study upon signing informed consent. 2. Patients who discontinued the core study due to unsatisfactory therapeutic effect at their Visit 14 (Week 16) or a later visit may enter the extension study within three weeks of completing the study discontinuation visit of the core study, provided that at their discontinuation visit they meet the criteria below. Patients who do not enter the extension study within 3 weeks of completing the study discontinuation visit of the core study, will have an additional baseline visit (Visit 17) and must meet the criteria below: * The number of tender joints is the same or more than the core study baseline OR, * The number of swollen joints is the same or more than the core study baseline OR, * There is no improvement compared with the core study baseline in at least three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, Health Assessment Questionnaire and CRP. 3. Women of childbearing potential must be using simultaneously double-barrier or two highly effective methods of contraception, (e.g. intra-uterine device plus condom, diaphragm plus condom, etc; hormone replacement as either oral or implantable is acceptable as one form), from the time of screening for the duration of the entire study, upto study completion and up to 16 weeks post last drug administration. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. 4. Male patients willing to use simultaneously two highly effective methods of contraception (e.g. intra-uterine device plus condom) for the duration of the entire study, up to study completion visit and up to 16 weeks post the last drug administration. Periodic abstinence and withdrawal are not acceptable methods of contraception.
Exclusion criteria
Exclusion criteria: 1. Patients for whom continued treatment with AIN457 in the extension is not considered appropriate by the treating physician. 2. Patients who were non-compliant or who demonstrated a major protocol deviation in the core CAIN457A2206 study. 3. Patients who discontinued from the core CAIN457A2206 study before Visit 14 (Week 16). 4. Female patients who are pregnant or lactating 5. Any active systemic infection within the past 2 weeks including a positive chest X-ray. 6. Positive human immunodeficient virus (HIV: ELISA and Western blot) test result, Hepatitis B surface antigen (HBsAg) or Hepatitis C test result, where patients have been re-tested. The following Exclusion Criteria as defined in the core trial [CAIN457A2206] will continue to be valid with minor revisions: 7. Positive Purified Protein Derivative (PPD) tuberculin skin test of * 5 mm at baseline, (where patients have been re-tested). A positive PPD test will be defined using the MMWR 2000 guidance, summarized as criteria for tuberculin positivity by risk group. A PPD test should not be done in subjects who had a tuberculosis vaccination in the past. These subjects will be eligible to participate if * according to local guidelines * latent tuberculosis can be excluded. For those study sites using QuantiFeron test a positive test at baseline (where patients have been re-tested) will exclude the subject from the participation in the study. If the result for either PPD or QuantiFeron test is indeterminate the subject will be excluded. 8. For previous use of immunosuppressive agents a wash-out period of at least 1 month or 5 half-lives, whatever is longer, is required. Immunosuppressive agent include but are not limited to cyclosporine, mycophenolate, tacrolimus, and 5-aminosalicylic acid (5-ASA). If on previous treatment with anti-TNF-* therapy (or other biological therapy), the following washout periods will be required for such patients to be eligible to participate in the trial. * Six (6)-months wash out prior to dosing for alefacept, rituxan and raptiva. * Three (3)-months washout prior to baseline for adalimumab and certolizumab. * Two (2)-months washout prior to baseline for etanercept and infliximab. * One (1) month washout prior to baseline for systemic immunosuppressants including, but not limited to azathioprine, cyclosporine and leflunomide. Patients on concomitant prednisone, Methotrexate (MTX) or SSZ can be included, whereby: * Prednisone should be kept at a stable dose 4 weeks before baseline and throughout the study and not exceed 10 mg/day. * MTX should be kept at a stable dose 4 weeks before baseline and throughout the study and not exceed 25 mg/week. * SSZ should be kept at a stable dose 4 weeks before baseline and throughout the study 9. Patients who are on NSAIDS should be kept at a stable dose 4 weeks before baseline and throughout the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the safety and tolerability of AIN457 administered i.v. initially up to 6 months (Part 1) with a possible extension of a further 6 months (Part 2) in patients with psoriatic arthritis who participated in the core CAIN457A2206 phase II proof-of-concept study | — |
Secondary
| Measure | Time frame |
|---|---|
| * To assess the immunogenicity of AIN457 * To assess the total IL-17 concentration in blood at steady-state * To assess the pharmacokinetics of AIN457 at steady state Exploratory Objective(s) * To explore the efficacy of AIN457 administered i.v. initially up to 6 months (Part 1) with a possible extension of a further 6 months (Part 2) as measured by ACR response criteria, PsARC response, DAS28, MASES, SPARCC and Leeds Dactylitis Index (LDI) basic. * To explore the effect of AIN457 on PASI scores in patients with coexisting psoriasis. * To explore the quality of life in psoriatic arthritis patients by using SF-36 and HAQ. * To model concentrations of free IL-17 based on measurements of total IL-17 and to link free levels of IL-17 to DAS28 by a preliminary AIN457 dose to DAS28 response time model to allow for dose-regimen estimations. The results from the exploratory objectives will be presented in a supplemental report as required. | — |
Countries
Netherlands
Outcome results
None listed