| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Psoriasis, a chronic inflammatory skin disorder, estimated to affect up to 2.5% of the world's population. Plaque-type psoriasis is the most common form of this disease. |
|
| E.1.1.1 | Medical condition in easily understood language |
| Moderate to severe plaque psoriasis |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10037153 |
| E.1.2 | Term | Psoriasis |
| E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
|
| 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 clinical efficacy of apremilast 30 mg BID, compared with placebo, in subjects with moderate to severe plaque psoriasis |
|
| E.2.2 | Secondary objectives of the trial |
- Evaluate the safety and tolerability of apremilast 30 mg BID, compared with placebo, in subjects with moderate to severe plaque psoriasis
- Evaluate the effect of apremilast 30 mg BID compared with placebo on quality of life
in subjects with moderate to severe plaque psoriasis |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Males or females, ≥ 18 years of age at the time of signing the informed consent document
2. 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. Diagnosis of chronic plaque psoriasis for at least 12 months prior to Screening
5. Have moderate to severe plaque psoriasis at Screening and Baseline as defined by
a. PASI score ≥ 12 and
b. BSA ≥ 10%, and
c. sPGA ≥ 3 (moderate)
6. Must be a candidate for phototherapy and/or systemic therapy
7. Must be in good health (except for psoriasis) as judged by the Investigator, based on medical history, physical examination, 12-lead ECG, clinical laboratories, and urinalysis
8. Must meet the following laboratory criteria
a. White blood cell count ≥ 3000/mm3 (≥ 3.0 x 109/L) and < 14,000/mm^3
(< 14 x 10^9/L)
b. Platelet count ≥100,000/μL (≥ 100 x 10^9/L)
c. Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
d. AST (SGOT) and ALT (SGPT) ≤ 2 x upper limit of normal (ULN)
e. Total bilirubin ≤ 2 mg/dL (34 μmol/L)
f. Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)
g. Hemoglobin A1c ≤ 9.0 %
9. 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 contraception† while on study medication and for at least 28 days after taking the last dose of study medication with either: 1) one highly effective form (non-oral hormonal, intrauterine device [IUD], tubal ligation, vasectomized partner); or 2) an oral hormonal contraceptive PLUS one additional form of barrier contraception (male or female latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane], diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge with spermicide); or 3) two forms of barrier contraception (male or female latex condom or nonlatex condom NOT made out of natural [animal] membrane [for example, polyurethane]) PLUS one of the following (diaphragm with spermicide, cervical cap with spermicide, contraceptive sponge with spermicide).
Note: The protocol language regarding contraception has been revised. As this study is fully enrolled, the updated language regarding contraception is included in Section 6.2 (Contraception Education) of this amendment.
† The female subject's chosen form of contraception must be effective by the time the female subject is randomized into the study (for example, hormonal contraception should be initiated at least 28 days before randomization).
10. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (male latex condom or nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane]) while on study medication and for at least 28 days after the last dose of study medication.
|
|
| E.4 | Principal exclusion criteria |
1. Other than psoriasis, history of any 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, which would place the subject at unacceptable risk if he/she were to participate in the study.
3. Any condition that confounds the ability to interpret data from the study.
4. Pregnant or breast feeding
5. History of allergy to any component of the IP
6. Hepatitis B surface antigen positive at Screening
7. Anti-hepatitis C antibody positive at Screening
8. AST (SGOT) and/or ALT (SGPT) > 1.5 X ULN and total bilirubin > ULN and/or
albumin < LLN
9. Active tuberculosis (TB) or a history of incompletely treated TB
10. Clinically significant abnormality on 12-Lead ECG at Screening
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. History of positive human immunodeficiency virus (HIV), or have congenital or
acquired immunodeficiency (eg, common variable immunodeficiency disease)
13. Active substance abuse or a history of substance abuse within 6 months prior to
Screening
14. 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.
15. 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)
16. Psoriasis flare or rebound within 4 weeks prior to Screening
17. Evidence of skin conditions that would interfere with clinical assessments
18. Topical therapy within 2 weeks of randomization (including but not limited to topical corticosteroids, topical retinoid or vitamin D analog preparations, tacrolimus,
pimecrolimus, or anthralin/dithranol). Exceptions: low-potency corticosteroids (Class 6 or 7; please refer to the Investigators’ Manual) will be allowed as background therapy for treatment of 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. An unmedicated skin moisturizer (eg, Eucerin®) will be also permitted for body lesions only. Subjects should not use these topical treatments within 24 hours prior to the clinic visit.
19. Systemic therapy for psoriasis within 4 weeks prior to randomization (including but not limited to cyclosporine, corticosteroids, methotrexate, oral retinoids, mycophenolate, thioguanine, hydroxyurea, sirolimus, sulfasalazine, azathioprine, fumaric acid esters)
20. Use of phototherapy within 4 weeks prior to randomization (ie, UVB, PUVA)
21. Adalimumab, etanercept, efalizumab, infliximab, or certolizumab pegol within 12 weeks prior to randomization
22. Alefacept, briakinumab, or ustekinumab within 24 weeks prior to randomization
23. Use of any investigational drug within 4 weeks prior to randomization, or 5
pharmacokinetic/pharmacodynamic half lives, if known (whichever is longer)
24. Prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources
25. Prior treatment with apremilast |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Proportion of subjects treated with either apremilast 30 mg BID or placebo who achieve at least a 75% reduction in PASI (PASI-75) at Week 16 from baseline |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| From Baseline (pre-dose) to Week 16 |
|
| E.5.2 | Secondary end point(s) |
Major Secondary
1) Proportion of subjects treated with either apremilast 30 mg BID or placebo with a sPGA score of clear (0) or almost clear (1) with at least 2 points reduction from baseline at Week 16 [Time Frame: From Baseline (pre-dose) to Week 16]
Efficacy
1) Percent change from Baseline in percent of affected BSA at Week 16 [Time Frame: From Baseline (pre-dose) to Week 16]
2) Percent change in the PASI score from the Baseline Visit at Week 16 [Time Frame: From Baseline (pre-dose) to Week 16]
3) Proportion of subjects who achieve PASI-50 at Week 16 [Time Frame: Week 16]
4) Change from Baseline in Pruritus VAS at Week 16 [Time Frame: From Baseline (pre-dose) to Week 16]
5) Change from baseline in DLQI total score at Week 16 [Time Frame: From baseline (pre-dose) to Week 16]
6) Change from baseline in Mental Component Summary (MCS) score of SF-36 at Week 16 [Time Frame: From Baseline (pre-dose) to Week 16]
7) Proportion of subjects who achieve both PASI-75 and sPGA score of clear (0) or almost clear (1) with at least 2 points reduction from Baseline at Week 16 [Time Frame: From Baseline (pre-dose) to Week 16]
8) Time to loss of PASI-75 response (loss of effect) during the Randomized Treatment Withdrawal Phase [Time Frame: Week 32 until approximately Week 52]
Safety
Safety as defined by:
- Type, frequency, severity, seriousness, and relationship of adverse events to apremilast [Time Frame: From the time of Informed Consent, through dosing, and for 28 days after the last dose of study medication.]
- Number of subjects who prematurely discontinue IP due to an adverse event [Time Frame: From the time of Informed Consent, through dosing, and for 28 days after the last dose of study medication.]
- Frequency of clinically significant changes in physical examination, vital signs, electrocardiogram, and/or laboratory findings [Time Frame: From the time of Informed Consent, through dosing, and for 28 days after the last dose of study medication.]
- Psoriasis flare or rebound [Time Frame: From the time of Informed Consent, through dosing, and for 28 days after the last dose of study medication.] |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| SEE ABOVE FOR TIME POINTS |
|
| 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 | No |
| 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 | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 25 |
| 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 |
| Australia |
| Canada |
| United States |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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
|
|
| 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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