A Study of the Impact of Apremilast (CC-10004) on Quality of Life, Efficacy, and Safety in Adults With Manifestations of Plaque Psoriasis and Impaired Quality of Life

A Phase 4, Multi-center, Randomized, Double-blind, Placebo-controlled Study of the Impact of Apremilast (CC-10004) on Quality of Life, Efficacy, and Safety in Subjects With Manifestations of Plaque Psoriasis and Impaired Quality of Life

The primary objective of the study is to assess the impact of treatment with apremilast 30 mg twice daily for 16 weeks, compared to placebo, on health-related quality of life (QOL) in adults with manifestations of plaque psoriasis and impaired quality of life.

Participants will be randomized 2 (apremilast):1 (placebo) in approximately 10 countries in Western Europe. Participants will be block-randomized to each of the manifestations of psoriasis (scalp psoriasis, nail psoriasis, palmoplantar psoriasis, genital psoriasis, and psoriasis in visible locations). Participants presenting with multiple manifestations will be allocated to the manifestation which is most severe, as determined by the participant. All manifestations will be assessed for efficacy at each study visit.

The study will consist of 4 phases:

• Screening Phase - up to 5 weeks (35 days)
• Double-blind Placebo-controlled Phase - Weeks 0 to 16 Participants will receive treatment with either apremilast or matched placebo.
• Apremilast Extension Phase - Weeks 16 through 52 All participants will be switched to (or continue with) apremilast at week 16 and will maintain this dosing through week 52.
• Post-treatment Observational Follow-up Phase 4-week post-treatment observational follow-up phase for all participants who complete the study on treatment or discontinue from the study treatment early.

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

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:

   1. Moderate to severe scalp psoriasis, defined as Scalp Physician Global Assessment (ScPGA) ≥ 3
   2. Nail psoriasis, defined as onycholysis and onychodystrophy in at least 2 fingernails
   3. Moderate to severe genital plaque psoriasis, defined as modified static Physicians Global Assessment of Genitalia (sPGA-G) ≥ 3
   4. Moderate to severe palmoplantar psoriasis, defined as Palmoplantar Psoriasis Physicians Global Assessment (PPPGA) ≥ 3
   5. 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.

Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:

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 or inverse psoriasis.
2. Subject has history of drug-induced psoriasis.
3. Subject has arthritis that requires systemic 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 hospitalization within the last 3 years prior to signing the informed consent.
8. Subjects with severe renal impairment, defined by estimated glomerular filtration rate (eGFR) or creatinine clearance (CLcr) 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 to any components of the IP (including placebo).
17. Subject has rare hereditary problem of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption.
18. Subject's most severe manifestation corresponds to a manifestation whose randomization block has already been fully enrolled.