Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) In Japanese Patients With Moderate-To-Severe Plaque-Type Psoriasis

A Phase 2B, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) In Japanese Subjects With Moderate-To-Severe Plaque-Type Psoriasis

This study will test the clinical effectiveness and safety of two orally administered doses of apremilast compared to placebo in Japanese patients with moderate-to-severe plaque-type psoriasis.

Study Overview

• Status: Completed
• Conditions: Psoriasis; Psoriatic Arthritis; Psoriasis Arthropatica
• Intervention / Treatment: Drug: Apremilast; Drug: Placebo

Detailed Description

This is a phase 2b, multicenter, randomized, double-blind, placebo-controlled study of the efficacy and safety of apremilast 20 mg twice a day (BID), apremilast 30 mg BID, and placebo in Japanese participants with moderate to severe plaque psoriasis.

• Study Type: Interventional
• Enrollment (Actual): 254
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 719-0373
    • Matsuo Clinic
  • Osaka, Japan, 530-0001
    • AMC Nishiumeda Clinic
  • Tokyo, Japan, 103-0028
    • Tokyo Center Clinic
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 814-0180
      • Fukuoka University Hospital
    • Fukuoka-shi, Fukuoka, Japan, 812-0013
      • Ekihigashi Hifuka Clinic
    • Fukuoka-shi, Fukuoka, Japan, 813-0042
      • Tsutsui Clinic Dermatology & Plastic Surgery
    • Fukuoka-shi, Fukuoka, Japan, 814-0013
      • Yano Hifuka Hinyokika Clini
    • Fukuoka-shi, Fukuoka, Japan, 815-0075
      • HATAMOTO Derma Clinic
    • Fukuoka-shi, Fukuoka, Japan, 819-0167
      • Tomoko Matsuda Dermatological Clinic
    • Iizuka-shi, Fukuoka, Japan, 820-0040
      • TASHIRO Dermatological Clinic
    • Itoshima-shi, Fukuoka, Japan, 819-1108
      • Okubo Skin Care and Clinic
    • Itoshima-shi, Fukuoka, Japan, 819-1116
      • Matsuda Dermatology Clinic For Skin, Hair, Nail Diseases
    • Kitakyushu, Fukuoka, Japan, 802-0077
      • Kitakyushu Municipal Medical Center
    • Kitakyushu, Fukuoka, Japan, 806-8501
      • Kyushu Kosei Nenkin Hospital
    • Kitakyushu-shi, Fukuoka, Japan, 800-0296
      • Kyusyu Rosai Hospital
    • Kurume, Fukuoka, Japan, 830-0011
      • Kurume University Hospital
    • Nishi-Ku, Fukuoka, Japan, 819-0373
      • Matsuo Clinic
    • Yame, Fukuoka, Japan, 834-0034
      • Yame General Hospital
  • Hokkaido
    • Abashiri-shi, Hokkaido, Japan, 093-0016
      • Kokubu Medical Office Abashiri Dermatology Clinic
    • Chitose-shi, Hokkaido, Japan, 066-0021
      • Chitose Dermatology Plastic Surgery Clinic
    • Chitose-shi, Hokkaido, Japan, 066-0064
      • Asanuma Dermatology Clinic
    • Kitami-shi, Hokkaido, Japan, 090-0832
      • Kokubu Dermatology
    • Sapporo-shi, Hokkaido, Japan, 060-0063
      • Sapporo Skin Clinic
    • Sapporo-shi, Hokkaido, Japan, 062-0042
      • Fukuzumi Dermatology Clinic
  • Hyogo
    • Kobe City, Hyogo, Japan, 653-0013
      • Kobe City Medical Center
  • Ibaraki
    • Hitachi, Ibaraki, Japan, 317-0077
      • Hitachi General Hospital
    • Inashiki-gun, Ibaraki, Japan, 300-0395
      • Tokyo Medical University Ibaraki Medical Center
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 213-8507
      • Teikyo University School of Medicine University Hospital
    • Kawasaki City, Kanagawa, Japan, 211-8510
      • Kanto Rosai Hospital
    • Kawasaki-shi, Kanagawa, Japan, 212-0016
      • Kawasaki Saiwai Clinic
    • Sagamihara, Kanagawa, Japan, 252-0392
      • Sagamihara National Hospital
    • Yokohama, Kanagawa, Japan, 213-8507
      • Yokohama City University Hospital
    • Yokohama-shi, Kanagawa, Japan, 220-6208
      • Queen's Square Medical Facilities
    • Yokohoma City, Kanagawa, Japan, 221-0825
      • Nomura Dermatology Clinic
    • Yokosuka, Kanagawa, Japan, 238-8558
      • Yokosuka Kyosai Hospital
  • Kumamoto
    • Kumamoto City, Kumamoto, Japan, 862-0975
      • Kumamoto Shinto General Hospital
    • Kumamoto-shi, Kumamoto, Japan, 860-0016
      • Kosumi lin
  • Osaka
    • Sakai-Shi, Osaka, Japan, 593-8324
      • Kume Derma Clinic
  • Saitama
    • Saitama-shi, Saitama, Japan, 330-0854
      • SANRUI Dermatology
  • Tochigi
    • Shimotsuke-shi, Tochigi, Japan, 329-0498
      • Jichi Medical University Hospital
    • Utsunomiya-shi, Tochigi, Japan, 321-0954
      • Sugai Dermatologist Park Side Clinic
  • Tokyo
    • Cyu-o-ku, Tokyo, Japan, 103-0016
      • Kayaba Dermatology Clinic
    • Hachioji, Tokyo, Japan, 192-0032
      • Tokai University School of Medicine
    • Inagi, Tokyo, Japan, 206-2801
      • Inagi Municipal Hospital
    • Itabasi-Ku, Tokyo, Japan, 174-0071
      • TSUTSUMI Clinic
    • Koto-ku, Tokyo, Japan, 136-0072
      • Koto Hospital
    • Koto-ku, Tokyo, Japan, 136-0074
      • Maruyama Dermatology Clinic
    • Nerima-ku, Tokyo, Japan, 178-0063
      • Oizumi Hanawa Clinic
    • Setagaya-ku, Tokyo, Japan, 158-0097
      • Naoko Dermatology Clinic
    • Setagaya-ku, Tokyo, Japan, 158-0094
      • Kitahara Dermatology Clinic
    • Shiba Minato-k, Tokyo, Japan, 108-0014
      • Mita Dermatology Clinic
    • Shinagawa-ku, Tokyo, Japan, 141-8625
      • NTT Medical Center Tokyo
    • Shinjyuku-ku, Tokyo, Japan, 160-0023
      • Tokyo Medical University Hospital
    • Suginami-ku, Tokyo, Japan, 166-0015
      • Taneda Dermatology Clinic
    • Tachikawa, Tokyo, Japan, 190-8531
      • Federation of National Public Service Personnel Mutual Aid Associations Tachikawa Hospital
  • Yamaguchi
    • Shimonoseki-shi, Yamaguchi, Japan, 750-0061
      • Shakaihoken Simonoseki Kosei Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female Japanese participants greater than or equal to 20 years of age.
• Diagnosis of chronic, stable plaque psoriasis for at least 6 months prior to screening as defined by: Psoriasis Area Severity Index (PASI) score ≥ 12 and BSA ≥ 10%.
• Psoriasis which is considered inappropriate for topical therapy (based on severity of disease and extent of affected area) or has not been adequately controlled or treated by topical therapy in spite of at least 4 weeks of prior therapy with at least one topical medication for psoriasis or per label.
• In otherwise good health based on medical history, physical examination, 12-lead electrocardiogram (ECG), serum chemistry, hematology, immunology, and urinalysis.

Exclusion Criteria:

• Other than psoriasis, history of any clinically significant and uncontrolled systemic diseases; any condition, including the presence of laboratory abnormalities, which would place the participant at unacceptable risk or confound the ability to interpret the data in the study.

Prior medical history of suicide attempt or major psychiatric illness requiring hospitalization within the last 3 years

• Pregnant or breastfeeding.
• History of or ongoing chronic or recurrent infectious disease.
• Active tuberculosis (TB) or a history of incompletely treated TB.
• Clinically significant abnormality on 12-lead ECG or on chest radiograph at screening.
• History of human immunodeficiency virus (HIV) infection or have congenital or acquired immunodeficiencies (eg, Common Variable Immunodeficiency).
• Hepatitis B surface antigen or hepatitis B core antibody positive at screening; positive for antibodies to hepatitis C at screening.
• Malignancy or history of malignancy, except for treated (ie, cured) basal cell or squamous cell in situ skin carcinomas or treated (ie, cured) cervical intraepithelial neoplasia or carcinoma in situ (CIN) of the cervix with no evidence of recurrence within previous 5 years.
• Psoriasis flare within 4 weeks of screening.
• Topical therapy within 2 weeks prior to randomization or systemic therapy for psoriasis or psoriatic arthritis within 4 weeks prior to randomization.
• Use of etretinate within 2 years prior to randomization for females of child bearing potential (FCBP) or within 6 months for males, and within 4 weeks prior to randomization for non-FCBP.
• Use of phototherapy: Ultraviolet light B (UVB), Psoralens and long-wave ultraviolet radiation (PUVA) within 4 weeks prior to randomization or prolonged sun exposure or use of tanning booths or other ultraviolet light sources.
• Use of adalimumab, etanercept, certolizumab pegol, abatacept, tocilizumab, golimumab or infliximab within 12 weeks prior to randomization; use of ustekinumab, alefacept or briakinumab within 24 weeks prior to randomization.
• Any investigational drug within 4 weeks prior to randomization.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Apremilast 20mg; Apremilast 20 mg tablets orally twice a day (BID)	Drug: Apremilast; 20 mg tablet BID for 68 weeks; Other Names: CC-10004; Otzela; Drug: Placebo; Placebo tablet BID for 16 weeks
Experimental: Apremilast 30mg; Apremilast 30 mg tablets orally BID	Drug: Apremilast; 20 mg tablet BID for 68 weeks; Other Names: CC-10004; Otzela; Drug: Placebo; Placebo tablet BID for 16 weeks
Placebo Comparator: Placebo; Identically-appearing placebo tablets BID for 16 weeks followed by participants being re-randomized in a blinded fasion to apremilast 20 mg or 30mg tablets BID for 52 weeks	Drug: Placebo; Placebo tablet BID for 16 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved a 75% Improvement (Response) From Baseline in the Psoriasis Area and Severity Index (PASI-75) at Week 16	PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement was missing.	Baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved a Static Physician's Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) With at Least 2 Point Reduction From Baseline to Week 16	The sPGA is a measure of psoriasis disease severity at the time of evaluation by the Investigator. It does not compare assessments across visits or rely on investigator recall or prior disease. The sPGA is a 6-point scale ranging from 0 (clear, except for residual discoloration) to 5 (severe; majority of plaques have severe thickness, erythema, and scaling). The investigator examines all of the lesions on the participant and assigns a score ranging from 0 to 5 for thickness, erythema and degree of scaling. Scores for thickness, erythema and scaling are then summed and the mean of these 3 scores equals the overall sPGA score.	Baseline to Week 16
Percent Change From Baseline in the Psoriasis Affected Body Surface Area (BSA) at Week 16	BSA is a measurement of involved skin. The overall BSA affected by psoriasis is estimated based on the palm area of the subject's hand (entire palmar surface or "handprint" including the fingers), which equates to approximately 1% of total body surface area.	Baseline to Week 16
Percent Change From Baseline in the Psoriasis Area and Severity Index (PASI) Score	The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI is a validated instrument that has become standard in clinical trials for psoriasis. The PASI scores range from 0 to 72, with higher scores reflecting a greater disease severity.	Baseline to Week 16
Percentage of Participants Who Achieved a 50% Improvement From Baseline (Response) Reduction in the PASI-50 at Week 16	PASI-50 response is the percentage of participants who achieved at least a 50% reduction (improvement) from baseline in PASI score at Week 16. The improvement in PASI score was used as a measure of efficacy. The PASI was a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness and scaling) and degree of skin surface area involvement on defined anatomical regions. PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, thickness, and scaling are scored on a scale of 0 (none) to 4 (very severe) on 4 anatomic regions of the body: head, trunk, upper limbs, and lower limbs. Degree of involvement on each of the 4 anatomic regions is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement). The PASI score was set to missing if any severity score or degree of involvement is missing.	Baseline to Week 16
Change From Baseline in Pruritus Visual Analogue Scale 100-mm (VAS) at Week 16	The pruritus visual analog scale (VAS) was used to measure the amount of itching and discomfort a participant experiences. Participant's assessment of pruritus (Itch) asked: On average, how much itch have you had because of your condition in the past week? Higher scores correspond to more severe symptom or disease. The participant places a vertical line on a 100-mm VAS on which the left-hand boundary represents no itch at all and the right-hand boundary represents the worst itch imaginable. The distance from the vertical line to the left-hand boundary is recorded. VAS scores range from 0 to 100 mm, where higher scores correspond to worse pruritis (itch).	Baseline to Week 16
Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16	Dermatology Life Quality Index (DLQI) was developed as a practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains 10 items dealing with the participants skin. With the exception of Item Number 7, the participant responds on a four-point scale, ranging from "Very Much" (score 3) to "Not at All" or "Not relevant" (score 0). 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, scores 3 or 0 respectively), 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 "A lot," "A little," or "Not at all" (scores 2, 1, or 0 respectively). The DLQI total score has a possible range from 0 to 30, with 30 corresponding to the worst quality of life, and 0 corresponding to the best.	Baseline to Week 16
Change From Baseline in Mental Component Summary (MCS) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 at Week 16	SF-36 is a 36-item general health status instrument often used in clinical trials and health services research. It consists of 8 scales: physical function (PF), role limitations-physical (RP), vitality (VT), general health perceptions (GH), bodily pain (BP), social function (SF), role limitations-emotional (RE), and mental health (MH). Scale scores range from 0 to 100, with higher scores indicating better quality of life (better functioning)	Baseline to Week 16
Number of Participants Who Achieved an American College of Rheumatology Criteria (ACR) 20% Improvement (ACR 20)	The ACR 20 is defined as a 20% improvement in joint tenderness (78 joint count) and joint swelling scores (76 joint count) compared to baseline plus 20% improvements in 3 of the following 5 assessments (compared to baseline): subject global assessment of disease activity (measured on a 100-mm visual analog scale [VAS]); physician global assessment of disease activity (measured on a 100-mm VAS); subject self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI] score); subject assessment of pain (measured on a 100-mm VAS); and CRP level.	Baseline to Week 16
Percent Change From Baseline Psoriatic Arthritis Pain Visual Analogue Scale (VAS)	Change from baseline in psoriatic arthritis pain 100-mm VAS; The participant places a vertical line on a 100-mm VAS on which the left-hand boundary represents no pain at all and the right-hand boundary represents the worst possible pain. The distance from the vertical line to the left-hand boundary is recorded.	Baseline to Week 16
Percent Change From Baseline in Physical Function Assessment Using the Health Assessment Questionnaire Disability Index (HAQ-DI)	Change from baseline in physical function assessment using HAQ-DI; The HAQ-DI is a 20-question, self-administered instrument that measures the subject's functional ability on a 4-level difficulty scale (0-3, with 0 representing normal or no difficulty; and 3 representing inability to perform). Eight categories of functioning are included: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities.	Baseline to Week 16
Number of Participants With Adverse Events (AE) in the Placebo Controlled Phase	An AE was any noxious, unintended, or untoward medical occurrence, that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose.	Baseline to Week 16
Number of Participants With Adverse Events (AE) in the During the Apremilast-exposure Period	An AE was any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the participant's health, including laboratory test values regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) was considered an AE. A serious AE (SAE) is any untoward adverse event that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly or birth defect, or a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. An AE is a treatment emergent AE if the AE start date is on or after the date of the first dose of study drug and no later than 28 days after the last dose.	From the first dose of apremilast (either Week 0 or Week 16 for participants originally randomized to placebo who were re-randomized at Week 16) until 28 days after the last dose of apremilast.

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

General Publications

• Ohtsuki M, Okubo Y, Komine M, Imafuku S, Day RM, Chen P, Petric R, Maroli A, Nemoto O. Apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of Japanese patients with moderate to severe plaque psoriasis: Efficacy, safety and tolerability results from a phase 2b randomized controlled trial. J Dermatol. 2017 Aug;44(8):873-884. doi: 10.1111/1346-8138.13829. Epub 2017 Apr 9.
• Ohtsuki M, Kubo H, Morishima H, Goto R, Zheng R, Nakagawa H. Guselkumab, an anti-interleukin-23 monoclonal antibody, for the treatment of moderate to severe plaque-type psoriasis in Japanese patients: Efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled study. J Dermatol. 2018 Sep;45(9):1053-1062. doi: 10.1111/1346-8138.14504. Epub 2018 Jun 15.

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2013
• Primary Completion (Actual): November 20, 2014
• Study Completion (Actual): December 15, 2015

Study Registration Dates

• First Submitted: May 24, 2013
• First Submitted That Met QC Criteria: November 13, 2013
• First Posted (Estimate): November 20, 2013

Study Record Updates

• Last Update Posted (Actual): May 7, 2020
• Last Update Submitted That Met QC Criteria: April 28, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Psoriasis; Psoriatic Arthritis
• Additional Relevant MeSH Terms: Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Arthritis; Psoriasis; Arthritis, Psoriatic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 4 Inhibitors; Thalidomide; Apremilast
• Other Study ID Numbers: CC-10004-PSOR-011

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