E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Psoriatic arthritis (PsA), which belongs to seronegative spondyloarthropathies (SpA). |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037160 |
E.1.2 | Term | Psoriatic arthritis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy of AIN457 at 6 weeks based on the proportion of patients achieving ACR 20 response
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E.2.2 | Secondary objectives of the trial |
To evaluate the proportion of patients achieving at least 20% improvement as measured by ACR response criteria at other time points
To evaluate the proportion of patients achieving at least 50% and 70% improvement as measured by ACR response criteria
To evaluate the proportion of patients achieving at least 20%, 50% and 70% improvement as measured by PsARC response criteria
To evaluate the response as measured by DAS28
Response as measured by the MASES and Leeds Enthesis index
To evaluate PASI scores in patients with coexisting psoriasis
To assess the safety and tolerability in PsA patients
To assess the pharmacokinetics in PsA patients
To assess the pharmacodynamics of AIN457 in synovial tissues obtained by biopsy of effected joints at baseline and week 6 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males or females, aged 18-65 at time of consent.
2. All female subjects must have negative pregnancy test results at screening (urine) 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.
• 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 4 months following the completion of the study.
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 ≥ 40 (VAS 0-100mm) c) inflammatory pain ≥ 40 (VAS 0-100mm) d) disease is inadequately controlled on at least one DMARD given for at least three months at the maximum tolerated dose e) 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), γ 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 |
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E.4 | Principal exclusion criteria |
1. Currently have any of the following: joint diseases:
a) arthritis fulfilling classification criteria for RA; b) seronegative spondylarthropathy that fulfills classification criteria of ankylosing spondylitis (mod NY criteria); c) a positive CCP ELISA result past or present
2. Currently 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.
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. Recent previous treatment with anti-TNF-α therapy (or other biological therapy), immunosuppressive agents such as cyclosporine, mycophenolate, pimecrolimus, or tacrolimus. Washout periods are described in protocol.
• 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 (see protocol).
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 exception of psoriatic arthritis or other disease which in the clinical judgment of the investigator would make the patient unsuitable for the trial.
10. Subjects with active or history of clinically significant cardiac abnormalities, for example:
• Requiring drugs with QT-prolonging properties.
• QTc >450msec long QT-syndrome (own or with a family history) or with a family history of sudden unexplained death.
• LBBB, or subjects who have been hospitalized for heart failure of cardiac etiology in the previous 6 months, and subjects who have significant and persistent left-ventricular dysfunction (LVEF < 40%).
• History of, in the preceding 3 months, significant and persistent arrhythmias such as ventricular fibrillation or tachycardia, or atrial fibrillation or flutter.
• Symptomatic coronary artery disease
• Presence of severe cardiac disease (NYHA ≥ III) and/or abnormal ECG, considered by the investigator to be unsafe for the study.
11. History of renal trauma, glomerulonephritis, or patient with one kidney.
12. History of severe hypersensitivity to any biological agents (antibody or soluble receptor), a history of serious allergic reaction, collagen disease, neurological disease (including demyelinating disease).
13. History of malignancy (other than basal cell carcinoma or adequately treated carcinoma-in-situ of the cervix).
14. Unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access to veins.
15. Conditions associated with an immune-compromised condition such as recent major surgical procedure; history of drug or alcohol abuse within the 6 months prior to dosing.
16. Purified Protein Derivative (PPD) tuberculin skin test reaction of ≥ 10 mm at screening or within 6 months prior to the screening visit, according to national guidelines. For details see protocol.
17. Liver disease or liver injury as indicated by abnormal liver function tests such as SGOT (AST), SGPT (ALT), γ-GGT, alkaline phosphatase, or serum bilirubin. For guidance see protocol.
18. Total WBC count which falls outside the range of 4500–11,000/µl, or platelets <100,000/µl at screening.
19. History of severe hypersensitivity to any biological agents (antibody or soluble receptor), including serious allergic reaction (hypotension, wheezing, urticaria), lupus-like syndrome, or demyelinating disease.
20. Donation or loss of 400 mL or more of blood within 8 weeks prior to dosing or longer if required by local regulation. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of ACR20 responders. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Proteomics, metabonomics, soluble markers |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 5 |