An Efficacy and Safety Study of Apremilast (CC-10004) in Subjects With Moderate to Severe Genital Psoriasis (DISCREET)

A Phase 3, Multicenter, Randomized, Placebo-Controlled, Double Blind-Study of the Efficacy and Safety of Apremilast (CC-10004) in Subjects With Moderate to Severe Genital Psoriasis

This Phase 3 multicenter, randomized, placebo-controlled, double-blind study is designed to evaluate the efficacy and safety of apremilast in subjects with moderate to severe genital psoriasis (modified sPGA-G ≥3, moderate or severe).

Approximately 286 subjects with moderate to severe genital psoriasis will be randomized 1:1 to receive either apremilast 30 mg BID or placebo for the first 16 weeks.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Other: Placebo; Drug: Apremilast

Detailed Description

The study will consist of four phases:

• Screening Phase - up to 35 days

• Double-blind Placebo-controlled Phase - Weeks 0 to 16

  - Subjects will be randomly assigned to either apremilast 30 mg tablets orally BID or placebo tablets (identical in appearance to apremilast 30 mg tablets) orally BID.

• Apremilast Extension Phase - Weeks 16 to 32

  - All subjects will be switched to (or continue with) apremilast 30 mg BID. All subjects will maintain this dosing through Week 32.

• Observational Follow-up Phase - 4 weeks - Four-week Post-Treatment Observational Follow-up Phase for all subjects who complete the study or discontinue the study early.

• Study Type: Interventional
• Enrollment (Actual): 289
• Phase: Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Centre Hospitalier Universitaire Saint Pierre
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St Luc
  • Leuven, Belgium, 3000
    • Uz Leuven
• Canada
  • St. John's, Canada, A1E 1V4
    • Skincare Studio
  • Ontario
    • London, Ontario, Canada, N6A 3H7
      • Guenther Dermatology Research Centre
    • Markham, Ontario, Canada, L3P1X2
      • Lynderm Research Inc
    • Waterloo, Ontario, Canada, N2J 1C4
      • K Papp Clinical Research
  • Quebec
    • Saint-Jerome, Quebec, Canada, J7Z 7E2
      • Dre Angelique Gagne-Henley M.D. Inc
• France
  • Lille, France, 59037
    • Hopital Claude Huriez CHRU Lille
  • Nice, France, 06202
    • CHU de Nice Archet I
  • Pessac, France, 33604
    • Centre Hospitalier Universitaire (CHU) de Bordeaux - Hopital Saint-Andre
  • Toulouse, France, 31000
    • Larrey University Hospital
• Germany
  • Berlin, Germany, 10789
    • ISA - Interdisciplinary Study Association GmbH
  • Bonn, Germany, 53127
    • Universitaetsklinikum Bonn
  • Erlangen, Germany, 91054
    • Hautklinik Universitatsklinikum Erlangen
  • Frankfurt am Main, Germany, 60590
    • Universitätsklinikum Frankfurt
  • Luebeck, Germany, 23538
    • Universitaetsklinikum Schleswig-Holstein, Campus Luebeck
  • Mainz, Germany, 55101
    • UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz
• Italy
  • Ancona, Italy, 60020
    • Ospedali Riuniti di Ancona
  • Grosseto, Italy, 58100
    • Presidio Ospedaliero della Misericordia
  • LAquila, Italy, 67100
    • Azienda Sanitaria Locale 1 Ospedale Regionale San Salvatore
  • Padova, Italy, 35128
    • Azienda Ospedaliera di Padova
  • Reggio Calabria, Italy, 89124
    • Azienda Ospedaliera Bianchi Melacrino Morelli
  • Terracina, Italy, 04019
    • Universita degli Studi di Roma La Sapienza Ospedale A Fiorini di Terracina
  • Trieste, Italy, 34125
    • Azienda Sanitaria Universitaria Integrata di Trieste
• Puerto Rico
  • San Juan, Puerto Rico, 00917
    • gcm Medical Group, Psc
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham
  • California
    • Fountain Valley, California, United States, 92708
      • First Oc Dermatology
    • Santa Monica, California, United States, 90404
      • Clinical Science Institute
  • Florida
    • Margate, Florida, United States, 33073
      • Glick Skin Institute
    • Miami, Florida, United States, 33144
      • International Dermatology Research, INC
  • Georgia
    • Macon, Georgia, United States, 31217
      • Skin Care Physicians of Georgia
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Dawes Fretzin Clinical Research Group, LLC
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Adult and Pediatric Dermatology
  • Massachusetts
    • Beverly, Massachusetts, United States, 01915
      • ActivMed Practices and Research Inc
    • Boston, Massachusetts, United States, 02115
      • Brigham and Womens Hospital
  • Nevada
    • Henderson, Nevada, United States, 89052
      • J Woodson Dermatology and Associates
    • Las Vegas, Nevada, United States, 89144
      • Las Vegas Dermatology
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03766
      • Dartmouth Hitchcock Medical Center
    • Portsmouth, New Hampshire, United States, 03801
      • ActivMed
  • New York
    • Stony Brook, New York, United States, 11790
      • Stony Brook Dermatology Associates
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Dermatology Consulting Services
  • Ohio
    • Athens, Ohio, United States, 45701
      • Oakview Dermatology
    • Gahanna, Ohio, United States, 43230
      • Ohio State University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Paddington Testing Company Inc
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Clinical Partners LLC
  • Texas
    • Houston, Texas, United States, 77004
      • Center for Clinical Studies
    • Pflugerville, Texas, United States, 78660
      • Austin Institute for Clinical Research
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Virginia Clinical Research Inc
  • Washington
    • Bellevue, Washington, United States, 98004
      • Bellevue Dermatology Clinic
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Dermatology Center for Skin Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 have a diagnosis of chronic plaque psoriasis for at least 6 months prior to signing the ICF.
3. Subject must have a diagnosis of moderate or severe psoriasis of the genital area at Screening and Baseline.
4. Subject must have a diagnosis of moderate or severe psoriasis at Screening and Baseline.
5. Subject must have plaque psoriasis (BSA ≥ 1%) in a non-genital area at both Screening and Baseline.
6. Subject must have been inadequately controlled with or intolerant of topical therapy, or topical therapy is inappropriate for the treatment of psoriasis affecting the genital area.
7. Subject must be in good health (except for psoriasis) as judged by the investigator, based on medical history, physical examination, clinical laboratories, and urinalysis.
8. Subject must meet laboratory criteria

Exclusion Criteria:

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

1. Subject has any significant medical condition or laboratory abnormality, that would prevent the subject from participating in the study.
2. Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
3. Subject has positive Hepatitis B surface antigen or anti-hepatitis C antibody at Screening.
4. Subject has active tuberculosis (TB) or a history of incompletely treated TB.
5. Subject has prior history of suicide attempt at any time in the subject's life time prior to signing the informed consent and randomization, or major psychiatric illness requiring hospitalization within the last 3 years prior to signing the informed consent.
6. Subject has current or planned therapies that may have a possible effect on psoriasis of the body and/or genital area during the course of the treatment phase of the trial
7. Subject had prior treatment with apremilast.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A- Apremilast with Placebo; Subjects randomized to the apremilast 30 mg BID treatment group will receive apremilast 30 mg tablets orally twice daily for the first 16 weeks Subjects randomized to the placebo treatment group will receive placebo tablets (identical in appearance to apremilast 30 mg tablets) orally twice daily for the first 16 weeks	Other: Placebo; Oral; Drug: Apremilast; Oral; Other Names: CC-10004, Otezla
Experimental: Arm B - Apremilast 30 mg; All subjects will receive apremilast 30 mg tablets orally twice daily after the Week 16 Visit through the end of the Apremilast Extension Phase of the study	Drug: Apremilast; Oral; Other Names: CC-10004, Otezla

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Modified sPGA-G Response at Week 16	The modified sPGA-G is the assessment by the Investigator of the participant's psoriasis lesions' overall disease severity in the genital area at the time of evaluation. The modified sPGA-G is a 5-point scale ranging from clear (0), almost clear (1), mild (2), moderate (3), to severe (4), incorporating an assessment of the severity of the 3 primary signs of the disease: erythema, plaque elevation, and scaling. A modified sPGA-G response is defined as modified sPGA-G score of clear (0) or almost clear (1) and with ≥ 2-point reduction from Baseline at Week 16. Missing values were imputed using the multiple imputation (MI) method. Two-sided 95% confidence intervals (CIs) for the within-group proportions were based on the Wilson-score method.	Baseline and Week 16 of the Placebo-controlled Phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Static Physician Global Assessment (sPGA) Response at Week 16	The sPGA is the assessment by the Investigator of the overall disease severity at the time of evaluation. The sPGA is a 5-point scale ranging from 0 (clear), 1 (almost clear), 3 (moderate) to 4 (severe), incorporating an assessment of the severity of the 3 primary signs of the disease: erythema, scaling and plaque elevation. An sPGA response is defined as sPGA score of clear (0) or almost clear (1) and with ≥ 2-point reduction from Baseline at Week 16. Missing values were imputed using the MI method. Two-sided 95% CIs for the within-group proportions were based on the Wilson-score method.	Baseline and Week 16 of the placebo-controlled phase
Percentage of Participants With a Genital Psoriasis Itch Numeric Rating Scale (GPI-NRS) Response at Week 16	The GPI-NRS is a self-reported measure where participants were asked to assess their psoriasis symptoms in the genital area and select a number on a scale of 0-10, where 0 represents no itch, and 10 represents the worst imaginable itch. A GPI-NRS response is defined as ≥ 4 point reduction (improvement) from Baseline. Missing values were imputed using the MI method. Two-sided 95% CIs for the within-group proportions were based on the Wilson-score method.	Baseline and Week 16 of the placebo-controlled phase
Change From Baseline in Affected Body Surface Area (BSA) at Week 16	The BSA is a measurement of involved skin over the whole body. The overall BSA affected by psoriasis is estimated based on the palm area of the participant's hand. The surface area of the whole body is made up of approximately 100 palms or "handprints" (each entire palmar surface or "handprint" equates to approximately 1% of total BSA). A negative change from Baseline indicates a reduction of affected BSA. Based on mixed-effect model for repeated measures (MMRM) model.	Baseline and Week 16 of the placebo-controlled phase
Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16	The DLQI is a 10 item questionnaire dealing with the participant's skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from 0 (not at all) to 3 (very much). Item Number 7 is a multi-part item, the first part of which ascertains whether the participant's skin prevented them from working or studying (Yes or No), and if "No," then the participant is asked how much of a problem the skin has been at work or study over the past week, with response alternatives being 0 (not at all), 1 (a little) and 2 (a lot). Total scores have a possible range of 0-30, where 0 represents the best score, and 30 represents the worst health-related quality of life. A negative change from Baseline indicates an improvement in health-related quality of life scores.	Baseline and Week 16 of the placebo-controlled phase
Change From Baseline in Genital Psoriasis Symptoms Scale (GPSS) Total Score at Week 16	The GPSS is a self-reported measure where participants were asked to assess each of their psoriasis symptoms (itch, pain, discomfort, stinging, burning, redness, scaling, and cracking) in the genital area and select a number on a scale of 0-10, where 0 represents no symptoms, and 10 represents the worst imaginable. Results from each symptom assessment were summed to generate a total GPSS score ranging from 0 (no genital psoriasis symptoms) to 80 (worst imaginable genital psoriasis symptoms). A negative change from Baseline indicates an improvement in genital psoriasis symptoms.	Baseline and Week 16 of the placebo-controlled phase

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• Merola JF, Parish LC, Guenther L, Lynde C, Lacour JP, Staubach P, Cheng S, Paris M, Picard H, Deignan C, Jardon S, Chen M, Papp KA. Efficacy and safety of apremilast in patients with moderate-to-severe genital psoriasis: Results from DISCREET, a phase 3 randomized, double-blind, placebo-controlled trial. J Am Acad Dermatol. 2024 Mar;90(3):485-493. doi: 10.1016/j.jaad.2023.10.020. Epub 2023 Oct 16.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2019
• Primary Completion (Actual): September 23, 2021
• Study Completion (Actual): February 9, 2022

Study Registration Dates

• First Submitted: December 14, 2018
• First Submitted That Met QC Criteria: December 14, 2018
• First Posted (Actual): December 17, 2018

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Plaque Psoriasis; CC-10004; Apremilast; Genital Psoriasis
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Apremilast
• Other Study ID Numbers: CC-10004-PSOR-025; U1111-1224-6850 (Registry Identifier: WHO); 2018-002608-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No