| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Psoriatic arthritis, an inflammatory arthritis that occurs in 6 to 39% of patients with psoriasis. |
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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 |
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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 |
| The primary objective of the study is to evaluate the clinical efficacy of 2 doses of apremilast (20 mg or 30 mg orally BID) compared with placebo, on the signs and symptoms of psoriatic arthritis (PsA) after 24 weeks` administration |
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| E.2.2 | Secondary objectives of the trial |
| - To evaluate the following in subjects with active PsA who are treated with 2 doses of apremilast of placebo for up to 24 weeks: - safety and tolerability - physical function - fatigue - clinical disease activity - To evaluate the following in subjects with active PsA who are treated with 2 doses of apremilast of placebo for up to 52 weeks: - safety and tolerability - efficacy - physical function - fatigue - clinical disease activity To evaluate the efficacy, safety, and tolerability of 2 doses of apremilast during up to 5 years` administration to subjects with active PsA |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Male or female, aged ≥ 18 years at time of consent. 2. Must understand and voluntarily sign an informed consent document prior to any study related assessments/ procedures being conducted. 3. Able to adhere to the study visit schedule and other protocol requirements. 4. Have a documented diagnosis of PsA (by any criteria) of ≥ 6 months’ duration. 5. Meet the CASPAR criteria for PsA at time of screening. 6. Have ≥ 3 swollen AND ≥ 3 tender joints, despite prior or current treatment with DMARDs (ie, therapeutic DMARD failure). 7. Be receiving treatment on an outpatient basis. 8. If taking methotrexate, leflunomide, or sulfasalazine, must have been treated for at least 16 weeks and on a stable dose (oral or parenteral methotrexate ≤ 25 mg/week; leflunomide ≤ 20 mg/day; sulfasalazine ≤ 2 g/day) for at least 4 weeks prior to screening and through Week 24 of the study. One reduction in DMARD dose will be permitted after Week 24. 9. If taking oral corticosteroids, must be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 1 month prior to screening. 10. If taking NSAIDs or narcotic analgesics, must be on stable dose for at least 2 weeks prior to screening and until they have completed the Week 24 study visit. 11. Low potency topical corticosteroids (Appendix M or locally-available equivalent) will be allowed as background therapy for treatment of psoriasis on the face, axillae and groin in accordance with the manufacturers’ suggested usage during the course of the study. Subjects with scalp psoriasis will be permitted to use coal tar shampoo and/or salicylic acid scalp preparations on scalp lesions. A non-medicated skin emollient (eg, Eucerin cream) will also be permitted for body lesions only. Subjects must not use these treatments within 24 hours prior to the clinic visit. 12. Meet the following laboratory criteria: - White blood cell count ≥ 3000/mm3 (≥ 3.0 x 10^9/L) and < 14,000/mm3 (< 14 x 10^9/L) - Platelet count ≥100,000/mm3 (≥ 100 x 10^9/L) - Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L) - AST (SGOT) and ALT (SGPT) ≤ 2 X upper limit of normal (ULN) - Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L) - Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L) - Hemoglobin A1c ≤ 9.0% 13. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane]) while on study medication and for a least 28 days after the last dose of study medication. 14. Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use 2 forms of contraception while on study medication and for at least 28 days after taking the last dose of study medication: one highly effective form (ie, hormonal, intrauterine device [IUD], tubal ligation, vasectomized partner) and one additional form (latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane], diaphragm, sponge). If one highly effective form of contraception cannot be used, then 2 forms of barrier contraception must be used, ie, latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane] with either of the following: sponge with spermicide or diaphragm with spermicide |
|
| E.4 | Principal exclusion criteria |
| 1. History of clinically significant (as determined by the Investigator) cardiac,endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic,immunologic disease, or other major uncontrolled disease. 2. Any condition, including the presence of laboratory abnormalities that places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. 3. Clinically significant abnormality on 12-lead ECG at Screening. 4. Pregnant or breast feeding. 5. History of allergy to any component of the investigational product (IP). 6. Hepatitis B surface antigen positive at screening. 7. Hepatitis C antibody positive at screening. 8. AST (SGOT) and/or ALT (SGPT) > 1.5X ULN and total bilirubin > ULN or albumin < LLN. 9. History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease). 10. Active tuberculosis or a history of incompletely treated tuberculosis. 11. Clinically significant abnormality based upon chest radiograph with at least PA view (radiograph must be taken within 12 weeks prior to Screening or during the Screening visit). An additional lateral view is strongly recommended but not required. 12. Active substance abuse or a history of substance abuse within 6 months prior to Screening. 13. Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening. Any treatment for such infections must have been completed at least 4 weeks prior to Screening. 14. Malignancy or history of malignancy (except for treated [ie, cured] basal-cell or squamous cell in situ skin carcinomas and treated [ie, cured] cervical intraepithelial neoplasia [CIN] or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years). 15. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization. 16. Erythrodermic, guttate, or pustular psoriasis. 17. Topical therapy for psoriasis, except as noted in the Inclusion Criteria, within 2 weeks of randomization (including but not limited to topical corticosteroids, topical retinoids or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin). 18. Rheumatic autoimmune disease other than PsA, including systemic lupus erythematosis (SLE), mixed connective tissue disease (MCTD), scleroderma, or polymyositis. 19. Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis (Appendix Q). 20. Prior history of or current inflammatory joint disease other than PsA (eg, gout, reactive arthritis, RA, ankylosing spondylitis, Lyme disease). 21. Use of the following systemic therapy(ies) within 4 weeks of randomization, including but not limited to cyclosporine or other calcineurin inhibitors, corticosteroids and small molecule DMARDs (except as noted in inclusion criteria), oral retinoids, mycophenolate, thioguanine, hydroxyurea, sirolimus, tacrolimus, azathioprine, fumaric acid esters. 22. Use of phototherapy within 4 weeks of randomization (ie, UVB, PUVA). 23. Use of adalimumab, etanercept, golimumab, infliximab, certolizumab pegol, or tocilizumab within 12 weeks of randomization. 24. Use of alefacept or ustekinumab within 24 weeks of randomization. 25. Previous treatment with any cell depleting therapies, including investigational agents (eg, rituximab, CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19, and anti-CD20). 26. Treatment with intravenous gamma globulin, plasmapheresis, or Prosorba column within 6 months of baseline. For complete list of exclusion criteria refer to the study protocol |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of subjects in each treatment group who achieve the American College of Rheumatology criteria for a 20% improvement (ACR 20), compared with baseline, after 24 weeks’ treatment |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | Yes |
| E.8.2.3.1 | Comparator description |
| - same IMP used at different dosage |
|
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 52 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| 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
|
| Fare riferimento al protocollo di studio |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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