Randomized, double-blind, placebo-controlled, multi-center, proof-of-concept study to assess the efficacy of AIN457 in patients with psoriatic arthritis - CAIN457A2206

• Conditions: Psoriatic arthritis (PsA), which belongs to seronegative spondyloarthropathies (SpA).; MedDRA version: 9.1Level: LLTClassification code 10037160Term: Psoriatic arthritis

• Registration Number: EUCTR2008-002628-27-GB
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-07-25
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 147

Inclusion Criteria

1. Males or females, aged 18-75 at time of consent.
2. All female subjects must have negative pregnancy test results at screening (serum) and baseline.
• Women of childbearing potential (WoCBP) must be using simultaneously double-barrier or two acceptable methods of contraception, (e.g., intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc., hormone replacement as either oral or implantable is acceptable as one form), from the time of screening and for the duration of the study, through study completion and for 4 months following study completion and for 6 months post last dose of AIN457.
• Postmenopausal females must have had no regular menstrual bleeding for at least two (2) years prior to initial dosing. If menopause is confirmed by a plasma FSH level of >40 IU/L at screening, pregnancy test will be required only at screening.
• Female subjects who report surgical sterilization must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and/or Principle Investigator and noted in the Relevant Medical History / Current Medical Conditions section of the CRF.
• If female subjects have male partners who have undergone vasectomy, the vasectomy must have occurred more than six (6) months prior to first dosing.
• Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
3. Male subjects willing to use simultaneously two acceptable methods of contraception (e.g. spermicidal gel plus condom) for entire duration of the study, up to the study completion visit and at least for 6 months post last dose of AIN457.
4. Eligibility for study participation should be based on a diagnosis of psoriatic arthritis in accordance with the CASPAR criteria plus the following mandatory criteria
a) involvement of at least three swollen and tender peripheral joints.
b) PGA = 4 (VAS 0-100mm).
c) inflammatory pain = 4 (VAS 0-100mm).
d) disease is inadequately controlled on least one DMARD given for at least three months at the maximum tolerated dose.
e) negative RF = 100 IU AND negative CCP ELISA test.
5. Able to communicate well with the investigator, and to understand and comply with the requirements of the study. Understand and sign the written informed consent.
6. No evidence of liver disease or liver injury as indicated by abnormal liver function tests such as SGOT (AST), SGPT (ALT), ? GGT, alkaline phosphatase, or serum bilirubin. The investigator should be guided by criteria as outlined under exclusion criteria.
7. Patients with a history of immunization against influenza (within past 12 months) and/or history of pneumococcal vaccination will be included. If not already immunized, vaccination is allowed to be completed (during flu season only) and such patients may be included after a 3-week window post immunization. Immunizations with attenuated life virus should be postponed until after completion of the study
8. History of inflammatory bowel disease will be recorded.
9. Patients with a previous diagnosis of seronegative spondylarthropathy and/or IBD can be included if they fulfill above criteria of PsA at screening.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1

Exclusion Criteria

1.Have any of the following: joint diseases:
a) arthritis fulfilling classification criteria for RA; b) seronegative spondylarthropathy that fulfills classification criteria of ankylosing spondylitis (NY criteria); c) a positive CCP ELISA result past or present.
2. Have drug-induced psoriasis (new onset or exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium).
3. Men who are planning to initiate a pregnancy while enrolled in the study or for 4 months following completion of the study, or who are not willing to follow the restrictions in inclusion criteria 3. Male or females patients who plan to conceive during the time course of the study and 6 months post last infusion of AIN457.
4. Participation in any clinical trial using an investigational drug within 4 weeks prior to initial dosing or five half-lives of the investigational agent, whichever is longer, and for any other limitation of participation based on local regulations.
5a Previous use of immunosuppressive agents a wash-out period of at least 1 month or 5 half-lives, whichever is longer, is required.
If on previous treatment with anti-TNF-a therapy (or other biological therapy), the following wash-out period will be required for such patients to be eligible:
• 6mths washout prior to alefacept dosing.
• 3mths wash-out prior ro baseline for adalimumab & certolizumab.
• 2mths wash-out prior to baseline for etanercept & infliximab.
• 1mth wash-out prior to baseline for systemic immunosuppressants.
In case of previous leflunomide treatment, a wash out with oral cholestyramine might be considered as an alternative wash-out procedure to increase the elimination of lefluomide. Based on the notion that cholestyramine reduces plasma levels of the active leflunomide metabolite by approximately 40% in 24 hours and by 49% in 48 hours, cholestryamine is to be given irally at a dose of 8 g t.i.d. daily for 10 days. The patient may then be dosed with study drug not earlier than 2 weeks after the start of the cholestyramine wash out procedure.
• 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.
5b. Patients who are on NSAIDS should be kept at a stable dose 4 weeks before baseline and throughout the study.
6. Within 1 month of randomization, received any systemic medications/treatments that could affect psoriasis or PASI evaluation including, but not limited to, injectable corticosteroids, retinoids, vitamin D analogs, psoralens, fumaric acid derivatives, or phototherapy.
7. Within 2 weeks of randomization, used topical medications/treatments that could affect psoriasis or PASI evaluation, including but not limited to, anthralin, calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, methoxsalen, pimecrolimus, and trimethylpsoralens.
8. Positive human immunodeficient virus (HIV: ELISA and Western blot) test result, Hepatitis B surface antigen (HBsAg) or Hepatitis C test result. Any active systemic infection within the past 2 weeks including a positive chest X-ray.
9. Current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, cerebral, psychiatric, chronic inflammatory diseases with the

Study & Design

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