| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| EARLY, OLIGOARTICULAR PSORIATIC ARTHRITIS |
|
| E.1.1.1 | Medical condition in easily understood language |
| Mild form of joint inflammation affecting individuals with the skin disorder, psoriasis. |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10037160 |
| E.1.2 | Term | Psoriatic arthritis |
| E.1.2 | System Organ Class | 100000004859 |
|
| 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 |
| To evaluate the efficacy of apremilast 30 mg BID +- NSAIDs and/or csDMARDs vs. Placebo +- NSAIDs and/or csDMARDs in subjects with early oligoarticular psoriatic arthritis (PsA), assessed by modified MDA (MDA-Joints). |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate the impact of treatment with apremilast 30 mg BID + NSAIDs and/or csDMARDs vs. Placebo NSAIDs and/or csDMARDs on disease activity in subjects with early oligoarticular PsA.
- To evaluate the impact of apremilast 30 mg BID +- NSAIDs and/or csDMARDs vs. Placebo +-NSAIDs and/or csDMARDs on patient-reported outcomes (PROs) in subjects with early oligoarticular PsA.
- To evaluate the safety and tolerability of apremilast 30 mg BID +- NSAIDs and/or csDMARDs vs. Placebo +-NSAIDs and/or csDMARDs in subjects with early oligoarticular PsA. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject is a male or female, ≥ 18 years at time of consent.
2. Subjects must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted.
3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
4. Subject must have a documented diagnosis of PsA (by any criteria) of ≥ 3 months but 24 months duration at the time of the Screening Visit.
5. Subject meets the CASPAR (Appendix B) criteria for PsA at the Screening Visit.
6. Subject must have a total number of swollen joints greater than 1 and equal or less than 4 (> 1 but 4 swollen joints) at the Screening Visit and confirmed prior to randomization at the Baseline Visit.
7. Subject must have a total number of tender joints greater than 1 and equal or less than 4 (> 1 but 4 tender joints) at Screening and confirmed prior to randomization at the Baseline Visit.
8. Subjects taking oral glucocorticosteroids must be on a stable dose of prednisone ≤ 10 mg/day or equivalent for at least 4 weeks prior to the Baseline Visit (Section 8.1).
9. For all regions, the local Regulatory Label for treatment with apremilast must be followed. For example, subjects in the EU must have had inadequate response or intolerance to a prior csDMARD.
10. Subjects taking 1 protocol-allowed csDMARD (methotrexate [MTX] or sulfasalazine [SSZ]) may enter the study provided that the duration of treatment is ≤6 months prior to the Baseline Visit and treatment is taken at a stable dose for at least 3 months prior to the Baseline Visit. See Permitted Medications (Section 8.1) for details describing dose criteria.
11. Subjects exposed to MTX or SSZ and stopped treatment due to intolerance or due to safety reasons may enter the study provided that treatment was stopped within at least 4 days of the Baseline Visit.
12. Subjects taking NSAIDs may enter the study provided that the dose is stable for at least 2 weeks prior to the Baseline Visit. Subjects may discontinue NSAIDs at any time up to and including the Baseline Visit, prior to study randomization.
13. Females of childbearing potential (FCBP)† must have a negative pregnancy test at Screening and the Baseline Visit. While on investigational product and for at least 28 days after taking the last dose of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options described below:
Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner’s vasectomy; OR
Option 2: Male or female condom (latex condom or non-latex condom NOT made out of natural [animal] membrane [for example, polyurethane]); PLUS one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide.
NOTE: Option 2 may not be acceptable as a highly effective contraception option in all countries per local guidelines/regulations.
A female of childbearing potential is defined as a sexually mature female who: 1) has not undergone a
hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both
ovaries) or 2) has not been postmenopausal for at least 24 consecutive months (that is, has had menses at any
time during the preceding 24 consecutive months).
The female subject’s chosen form of contraception must be effective by the time the female subject is screened into the study (for example, hormonal contraception should be initiated at least 28 days before screening).
14. Must be in general good health (except for psoriatic arthritis) as judged by the Investigator, based on medical history, physical examination, and clinical laboratories. (Note: The definition of good health means a subject does not have uncontrolled significant comorbid conditions). |
|
| E.4 | Principal exclusion criteria |
1. Prior use of >1 cs DMARD.
2. Prior exposure to a JAK-inhibitor, including tyk2 inhibitors and/or a biologic DMARD.
3. Use of intra-articular (IA) or intra-muscular (IM) glucocorticoid injection within 8 weeks before the Baseline Visit.
4. Use of leflunomide within 12 weeks of randomization. Subjects who stopped leflunomide and completed 11 days of treatment with cholestyramine (8 g, 3 x daily) prior to the Baseline Visit may enter the study.
5. Prior use of cyclosporine.
6. Prior treatment with apremilast, or participation in a clinical study, involving apremilast.
7. Use of any investigational drug within 4 weeks of the Baseline Visit, or 5 pharmacokinetic/pharmacodynamic half-lives, if known (whichever is longer).
8. History of clinically significant or uncontrolled disease (as determined by the Investigator), which places the subject at unacceptable risk if he/she were to participate in the study.
9. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study. Subjects with a creatinine clearance level less than 30 mL/min (estimated by the Cockcroft–Gault equation) will be considered to have severe renal impairment and will be excluded from the study.
10. Prior history of suicide attempt at any time in the subject’s lifetime prior to signing the informed consent, or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent.
11. Pregnant or breast feeding.
12. Active substance abuse or a history of substance abuse within 6 months prior to Screening.
13. History of allergy or hypersensitivity to any component of the investigational product.
14. History of positive human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).
15. Active tuberculosis or a history of incompletely treated tuberculosis.
16. 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 and the infection cured, at least 4 weeks prior to Screening and no new or recurrent infections prior to the Baseline Visit.
17. Malignancy or history of malignancy or myeloproliferative or lymphoproliferative disease within the past 3 years, except for treated (ie, cured) basal cell or squamous cell in situ skin carcinomas.
18. Major surgery (including joint surgery) within 8 weeks prior to the Screening Visit or planned major surgery within 6 months following the Baseline Visit.
19. Rheumatic autoimmune disease other than PsA, including, but not limited to: systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis, or fibromyalgia.
20. Prior history of or current inflammatory joint disease other than PsA (eg, gout, reactive arthritis, rheumatoid arthritis [RA], ankylosing spondylitis, Lyme disease), which confounds the ability to interpret data from the study.
21. Erythrodermic, guttate, or generalized pustular psoriasis at randomization. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| MDA-Joints: Proportion of subjects who achieved a clinical state of minimal disease activity defined MDA-Joints. Subjects must achieve <=1 SJC and TJC, plus 3 out of 5 of the remaining cut-off values (BSA <= 3%; Patient pain (VAS) <= 15; Patient global disease activity (VAS) <= 20; HAQ <= 0.5; Tender entheseal points <= 1 (based on Leeds Enthesitis Index - LEI). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
- cDAPSA remission or low disease activity
- Swollen Joint Count (SJC) <= 1
- Tender Joint Count (TJC) <= 1
- Patient's global assessment of disease activity
- Patient's assessment of pain
- Change from Baseline in the Psoriatic Arthritis Impact of Disease 12-item for clinical trials (PsAID-12) questionnaire.
- PASDAS good and moderate response |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 55 |
| 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 | No |
| 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 |
| Canada |
| Russian Federation |
| United States |
| Austria |
| Belgium |
| France |
| Germany |
| Italy |
| Netherlands |
| Spain |
| United Kingdom |
|
| 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
|
| The date of the last visit of the last subject to complete the post-treatment follow-up, or the date of receipt of the last data point from the last subject that is required for primary, secondary and/or exploratory analysis, as prespecified in the protocol, whichever is the later date. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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