| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10071117 |
| E.1.2 | Term | Plaque psoriasis |
| E.1.2 | System Organ Class | 100000004858 |
|
| 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 assess the impact of apremilast 30 mg twice daily (BID), compared to placebo, on health related quality of life (qol) in subjects with manifestations of plaque psoriasis and impaired quality of life at Week 16. |
|
| E.2.2 | Secondary objectives of the trial |
- To assess the efficacy and safety of apremilast 30 mg BID, compared to placebo in subjects with manifestations of plaque psoriasis and impaired quality of life at Week 16
- To assess the long-term effects of apremilast 30 mg BID, with respect to quality of life, efficacy, and safety at Weeks 32 and 52 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
2. Subject must understand and voluntarily sign an ICF 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 has diagnosis of chronic plaque psoriasis for at least 6 months prior to baseline, that cannot be controlled by topical therapy.
5. Subject has a PASI score ranging from ≥3 to ≤ 10 at baseline.
6. Subject has a DLQI score > 10 at baseline.
7. Subject has presence of ≥ 1 clinical manifestations of plaque psoriasis, defined as at least one of the following:
a. Moderate to severe scalp psoriasis, defined as Scalp Physician Global Assessment (ScPGA) ≥ 3
b. Nail psoriasis, defined as onycholysis and onychodystrophy in at least 2 fingernails
c. Moderate to severe genital plaque psoriasis, defined as modified static Physicians Global Assessment of Genitalia (sPGA-G) ≥ 3
d. Moderate to severe palmoplantar psoriasis, defined as Palmoplantar Psoriasis Physicians Global Assessment (PPPGA) ≥ 3
e. Moderate to severe plaque psoriasis in visible locations (dorsal hand, face, neck, and hairline) with static Physicians Global Assessment (sPGA) ≥ 3
8. Subject must be in general good health (except for psoriasis) 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 co-morbid conditions.)
9. Subject must have failed to respond to, or be contraindicated to, or intolerant to other systemic therapy including, but not limited to, cyclosporine, methotrexate, acitretin, psoralen and ultraviolet-A-light (PUVA), fumaric acid esters or biologic therapies.
10. Subjects (in Italy only) must be non-responder to, contraindicated to, or intolerant to other systemic therapy (including cyclosporine, methotrexate, or PUVA) AND also be contraindicated to, or intolerant to biologics.
11. Females of childbearing potential (FCBP)† must have a negative pregnancy test at Screening and Baseline. 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 nonlatex 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 randomized into the study (for example, hormonal contraception should be initiated at least 28 days before randomization). |
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| E.4 | Principal exclusion criteria |
1. Subject has any condition, including other inflammatory diseases or dermatologic conditions, which confounds the ability to interpret data from the study, including other types of psoriasis (ie, erythrodermic, or guttate), other than plaque psoriasis, inverse psoriasis.
2. Subject has history of drug-induced psoriasis.
3. Subject has arthritis that requires disease-modifying antirheumatic drug (DMARD) treatment.
4. Subject unable to avoid use of tanning booths for at least 4 weeks prior to baseline and during study.
5. Subject is currently enrolled in any other clinical trial involving an investigational product.
6. Other than psoriasis, subject has history of clinically significant or uncontrolled disease (as determined by the Investigator) including the presence of laboratory abnormalities, cardiac, endocrinologic, pulmonary, neurologic, psychiatric, hepatic, renal, hematologic, immunologic disease, or other major disease which places the subject at unacceptable risk if he/she were to participate in the study.
7. Prior history of suicide attempt at any time in the subject´s lifetime prior to signing the informed consent, or major psychiatric illness requiring hospitalisation witin the last 3 years prior to signing the einformed consent.
8. Subjects wiht severe renal impairment, defined by eGFR (estimated glomerular filtration rate) or CLcr (creatine clearance ) less than 30 mL/min, are also categorized as having Stage 4 Chronic Kidney Disease (CKD), and are excluded from the study.
9. 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.
10. 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.
11. Subject has received a live vaccine within 3 months of baseline or plans to do so during study.
12. Subject is a pregnant or breastfeeding (lactating) woman.
13. Subject has used topical therapy within 2 weeks of randomization (including, but not limited to, topical corticosteroids, retinoids or vitamin D analog preparations, tacrolimus, pimecrolimus, anthralin/dithranol, or moisturizers which contain urea or salicylic acid). Use of phototherapy within 4 weeks prior to randomization. Use of conventional systemic therapy or systemic corticosteroids within 4 weeks prior to randomization, except for conditions other than psoriasis or psoriatic arthritis. Use of biologic therapy within 5 pharmacokinetic half-lives.
14. Prior treatment with apremilast, or participation in a clinical study, involving apremilast.
15. Subject has any condition that confounds the ability to interpret data from the study.
16. Subject has history of allergy or hypersensitivity ot any components of the IP (including placebo).
17. Subject has rare hereditary problem of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Dermatology Life Quality Index (DLQI) - Proportion of subjects who achieve a ≥ 4-point reduction from baseline |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
1. DLQI: Proportion of subjects who achieve a ≥ 4-point reduction from baseline at Weeks 32 and 52
2. DLQI: Mean change from baseline at Weeks 16, 32, 52
3. Itch Numeric Rating Scale (NRS): Mean change from baseline in Itch NRS score at Weeks 16, 32, 52
4. Skin Discomfort/Pain Visual Analog Scale (VAS): Mean change from baseline in skin discomfort/pain VAS at Weeks 16, 32, 52
5. Body Surface Area (BSA): Mean percent change in BSA
affected by psoriasis at Weeks 16, 32, 52
6. Patient Benefit Index (PBI): Proportion of subjects who achieve PBI score of ≥ 1 at Weeks 16, 32, 52
7. Psoriasis Area Severity Index (PASI): Proportion of subjects who achieve PASI < 3 at Weeks 16,32,52
8. European Quality of Life 5-Dimension (EQ-5D): Mean percent change from baseline in EQ-5D score at Weeks 16 and 52
9. Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI: PSO): Mean change in WPAI domain scores at Weeks 16 and 52
10. Treatment-emergent Adverse Events: Frequency and incidence rate of any TEAE by SOC, PT, severity, and relationship of adverse events (AEs) to investigational product (IP) during double-blinded treatment and throughout the duration of the apremilast treatment.
11. Clinically significant changes in body weight, waist circumference, vital signs, and/or laboratory findings: Frequency of clinically significant changes in body weight, waist circumference, vital signs, and/or laboratory findings during double-blinded treatment and throughout the duration of the apremilast treatment. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Endpoints at Weeks 16, 32, 52
1. DLQI: Mean change from baseline
2. Itch Numeric Rating Scale (NRS)
3. Skin Discomfort/Pain Visual Analog Scale (VAS)
4. Body Surface Area (BSA)
5. Patient Benefit Index (PBI)
6. Psoriasis Area Severity Index (PASI)
Endpoint at Weeks 32 and 52
1. DLQI: Proportion of subjects who achieve a ≥ 4-point reduction from
baseline
Endpoints at Weeks 16 and 52
1. European Quality of Life 5-Dimension (EQ-5D)
2. Work Productivity and Activity Impairment Questionnaire: Psoriasis
(WPAI: PSO)
Endpoints during double-blinded treatment and throughout the duration of the apremilast treatment:
1. Treatment-emergent Adverse Events
2. Clinically significant changes in body weight, waist circumference, vital signs, and/or laboratory findings |
|
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Impact on Health-related Quality of Life (qol) |
|
| 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 | 21 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 57 |
| 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 |
| France |
| Germany |
| Italy |
| Spain |
| Switzerland |
| 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 pre-specified in the protocol, whichever is the later date. |
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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 | 2 |
| E.8.9.1 | In the Member State concerned months | 8 |
| 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 | 2 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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