Clinical trial NCT03774875: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Psoriasis
Keywords: Apremilast
CC-10004
Quality of life
Safety
Efficacy
Psoriasis manifestations
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2018-12-13
Enrollment: 277
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Achieved a ≥ 4-point Reduction From Baseline in Dermatology Life Quality Index (DLQI) at Week 16
timeFrame: Baseline and week 16
Secondary outcomes:
measure: Change From Baseline in DLQI at Week 16
timeFrame: Baseline and week 16
measure: Percent Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis at Week 16
timeFrame: Baseline and week 16
measure: Change From Baseline in Itch Numeric Rating Scale (NRS) Score at Week 16
timeFrame: Baseline and week 16
measure: Change From Baseline in Skin Discomfort/Pain Visual Analog Scale (VAS) at Week 16
timeFrame: Baseline and week 16
measure: Percentage of Participants Who Achieved a Psoriasis Area Severity Index (PASI) Score < 3 at Week 16
timeFrame: Week 16
measure: Percentage of Participants Who Achieved a Patient Benefit Index (PBI) Global Score of ≥ 1 at Week 16
timeFrame: Week 16
measure: Percent Change From Baseline in European Quality of Life 5-Dimension (EQ-5D) VAS Score at Week 16
timeFrame: Baseline and week 16
measure: Percent Change From Baseline in EQ-5D Index Score at Week 16
timeFrame: Baseline and week 16
measure: Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Psoriasis (WPAI: PSO) at Week 16: Percentage Work Time Missed
timeFrame: Baseline and week 16
measure: Change From Baseline in WPAI: PSO at Week 16: Percentage Work Impairment
timeFrame: Baseline and week 16
measure: Change From Baseline in WPAI: PSO at Week 16: Percentage Overall Work Impairment
timeFrame: Baseline and week 16
measure: Change From Baseline in WPAI: PSO at Week 16: Percentage Activity Impairment
timeFrame: Baseline and week 16
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Placebo-controlled Period
timeFrame: From first dose of study drug to week 16 or up to 28 days after last dose for participants who didn't enter the apremilast extension period.
measure: Number of Participants With Marked Laboratory Abnormalities During the Placebo-controlled Period
timeFrame: 16 weeks
measure: Change From Baseline in Blood Pressure During the Placebo-controlled Period
timeFrame: Baseline, week 2, week 4, and week 16
measure: Change From Baseline in Pulse Rate During the Placebo-controlled Period
timeFrame: Baseline and week 2, week 4, and week 16
measure: Change From Baseline in Body Weight During the Placebo-controlled Period
timeFrame: Baseline and week 2, week 4, and week 16
measure: Change From Baseline in Waist Circumference During the Placebo-controlled Period
timeFrame: Baseline and week 2, week 4, and week 16
measure: Percentage of Participants Who Achieved a ≥ 4-point Reduction From Baseline in DLQI at Weeks 32 and 52
timeFrame: Baseline, week 32 and week 52
measure: Change From Baseline in DLQI at Weeks 32 and 52
timeFrame: Baseline, week 32 and week 52
measure: Change From Baseline in Itch NRS Score at Weeks 32 and 52
timeFrame: Baseline, week 32 and week 52
measure: Change From Baseline in Skin Discomfort/Pain VAS at Weeks 32 and 52
timeFrame: Baseline, week 32 and week 52
measure: Percent Change From Baseline in BSA Affected by Psoriasis at Weeks 32 and 52
timeFrame: Baseline, week 32 and week 52
measure: Percentage of Participants Who Achieved a PBI Score of ≥ 1 at Weeks 32 and 52
timeFrame: Week 32 and week 52
measure: Percentage of Participants Who Achieved a PASI Score < 3 at Weeks 32 and 52
timeFrame: Week 32 and week 52
measure: Percent Change From Baseline in EQ-5D VAS Score at Week 52
timeFrame: Baseline and week 52
measure: Percent Change From Baseline in EQ-5D Index Score at Week 52
timeFrame: Baseline and week 52
measure: Change From Baseline in WPAI: PSO at Week 52: Percentage Work Time Missed
timeFrame: Baseline and week 52
measure: Change From Baseline in WPAI: PSO at Week 52: Percentage Work Impairment
timeFrame: Baseline and week 52
measure: Change From Baseline in WPAI: PSO at Week 52: Percentage Overall Work Impairment
timeFrame: Baseline and week 52
measure: Change From Baseline in WPAI: PSO at Week 52: Percentage Activity Impairment
timeFrame: Baseline and week 52
measure: Number of Participants With TEAEs During Apremilast Treatment
timeFrame: From first dose of apremilast up to 28 days after last dose; up to 40 weeks for participants initially randomized to placebo and 56 weeks for participants initially randomized to apremilast.
measure: Number of Participants With Marked Laboratory Abnormalities During Apremilast Treatment
timeFrame: From first dose of apremilast up to 28 days after last dose; up to 40 weeks for participants initially randomized to placebo and 56 weeks for participants initially randomized to apremilast.
measure: Change From Baseline in Blood Pressure at End of Apremilast Extension Period
timeFrame: Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52
measure: Change From Baseline in Pulse Rate at End of Apremilast Extension Period
timeFrame: Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52
measure: Change From Baseline in Body Weight at End of Apremilast Extension Period
timeFrame: Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52
measure: Change From Baseline in Waist Circumference at End of Apremilast Extension Period
timeFrame: Baseline (defined as the last value measured on or before the day of the first apremilast dose) and end of apremilast extension period; week 52, or earlier for participants who discontinued prior to week 52
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Research Site
city: Grenoble Cedex 9
country: France
facility: Research Site
city: Lyon Cedex 03
country: France
facility: Research Site
city: Paris Cedex 10
country: France
facility: Research Site
city: Pringy
country: France
facility: Research Site
city: Rouen Cedex
country: France
facility: Research Site
city: Saint Priest en Jarez
country: France
facility: Research Site
city: Toulouse Cedex 9
country: France
facility: Research Site
city: Valence
country: France
facility: Research Site
city: Valenciennes
country: France
facility: Research Site
city: Aachen
country: Germany
facility: Research Site
city: Augsburg
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bochum
country: Germany
facility: Research Site
city: Bonn
country: Germany
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: Frankfurt am Main
country: Germany
facility: Research Site
city: Gera
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Jena
country: Germany
facility: Research Site
city: Kiel
country: Germany
facility: Research Site
city: Langenau
country: Germany
facility: Research Site
city: Lübeck
country: Germany
facility: Research Site
city: Marburg
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Tübingen
country: Germany
facility: Research Site
city: Ulm
country: Germany
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
city: Catania
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Napoli, Campania
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Perugia
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Badalona
country: Spain
facility: Research Site
state: Cataluña
city: Alicante
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Manises
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Alcorcon
country: Spain
facility: Research Site
state: Madrid
city: Fuenlabrada
country: Spain
facility: Research Site
state: Madrid
city: Castellon de la Plana
country: Spain
facility: Research Site
city: Lugo
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Murcia
country: Spain
facility: Research Site
city: Salamanca
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Lausanne
country: Switzerland
facility: Research Site
city: Zurich
country: Switzerland
facility: Research Site
city: Zürich
country: Switzerland
facility: Research Site
city: Barnet
country: United Kingdom
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Brighton
country: United Kingdom
facility: Research Site
city: Bury Saint Edmunds
country: United Kingdom
facility: Research Site
city: Dumfries
country: United Kingdom
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: Exeter
country: United Kingdom
facility: Research Site
city: Gloucester
country: United Kingdom
facility: Research Site
city: Isleworth
country: United Kingdom
facility: Research Site
city: Leeds
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Newport
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Plymouth
country: United Kingdom
facility: Research Site
city: Redhill
country: United Kingdom
facility: Research Site
city: Southampton
country: United Kingdom
facility: Research Site
city: Stourbridge
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Mrowietz U, Barker J, Conrad C, Jullien D, Gisondi P, Flower A, Reddy J, Paris M, Picard H, Jardon S, Augustin M. Efficacy and safety of apremilast in patients with limited skin involvement, plaque psoriasis in special areas and impaired quality of life: Results from the EMBRACE randomized trial. J Eur Acad Dermatol Venereol. 2023 Feb;37(2):348-355. doi: 10.1111/jdv.18689. Epub 2022 Nov 14.