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Study to Evaluate Safety and Effectiveness of Oral Apremilast (CC-10004) in Patients With Moderate to Severe Plaque Psoriasis (ESTEEM 1)

2022年3月3日 更新者：Amgen

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

This study evaluated the effects of an called apremilast. Apremilast works by lowering some of the chemicals that affect psoriasis and therefore improves the symptoms of psoriasis. The purpose of this study was to test apremilast and compare its effects to placebo (an inactive substance which contains no medicine but is in the same form as the drug). This study was able to test for efficacy (improvement of signs and symptoms) and safety of apremilast in patients with moderate to severe psoriasis.

調査の概要

状態

完了

条件

介入・治療

研究の種類

介入

入学 (実際)

844

段階

  • フェーズ 3

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

Inclusion Criteria:

  1. Males or females, ≥ 18 years of age at the time of signing the informed consent document

  2. Diagnosis of chronic plaque psoriasis for at least 12 months prior to Screening

    a. Have moderate to severe plaque psoriasis at Screening and Baseline

  3. Must meet all laboratory criteria
  4. Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use 2 forms of contraception as described by the Study Doctor while on study medication and for at least 28 days after taking the last dose of study medication
  5. Male subjects (including those who have had a vasectomy) who engage in activity in which conception is possible must use barrier contraception (latex condom or any nonlatex condom NOT made out of natural [animal] membrane [eg, polyurethane]) while on study medication and for a least 28 days after the last dose of study medication.

Exclusion Criteria:

  1. Other than psoriasis, history of any clinically significant (as determined by the Investigator) or other major uncontrolled disease.

    .

  2. Pregnant or breast feeding
  3. History of allergy to any component of the study drug
  4. Hepatitis B surface antigen positive at Screening
  5. Anti-hepatitis C antibody positive at Screening
  6. Active tuberculosis (TB) or a history of incompletely treated TB
  7. Clinically significant abnormality on 12-Lead Electrocardiogram (ECG) at Screening
  8. Clinically significant abnormal chest x-ray
  9. History of positive human immunodeficiency virus (HIV), or have congenital or acquired immunodeficiency
  10. Active substance abuse or a history of substance abuse within 6 months prior to Screening
  11. Bacterial infections requiring treatment with oral or injectable antibiotics, or significant viral or fungal infections, within 4 weeks of Screening
  12. Malignancy or history of malignancy (except for treated [ie, cured] basal cell or squamous cell in situ skin carcinomas and treated [ie, cured] cervical intraepithelial neoplasia [CIN] or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years)
  13. Psoriasis flare or rebound within 4 weeks prior to Screening
  14. Evidence of skin conditions that would interfere with clinical assessments
  15. Topical therapy within 2 weeks of randomization
  16. Systemic therapy for psoriasis within 4 weeks prior to randomization
  17. Use of phototherapy within 4 weeks prior to randomization (ie, Ultraviolet B (UVB), psoralen and ultraviolet A (PUVA)
  18. Adalimumab, etanercept, infliximab, or certolizumab pegol within 12 weeks prior to randomization
  19. Alefacept, briakinumab, or ustekinumab within 24 weeks prior to randomization
  20. Use of any investigational drug within 4 weeks prior to randomization
  21. Prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources
  22. Prior treatment with apremilast

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：ランダム化
  • 介入モデル：並列代入
  • マスキング：4倍

武器と介入

参加者グループ / アーム
介入・治療
アクティブコンパレータ：Apremilast
Subjects initially randomized to apremilast 30 mg twice a day, and who demonstrate a PASI 75 response at Week 32 will be randomized (1 to 1) to either continue to receive apremilast 30 mg ) BID or to receive placebo (until effect is lost). At the time effect is lost, subjects will be treated with apremilast 30 mg twice a day for the duration of their participation in the study.
薬：アプレミラスト
他の名前：
  • CC-10004
  • オテズラ
薬：Placebo
Identical matching placebo
プラセボコンパレーター：Placebo
Subjects initially randomized to placebo, are assigned to apremilast 30 mg twice a day beginning at Week 16 for the duration of the subject's participation in the study.
薬：アプレミラスト
他の名前：
  • CC-10004
  • オテズラ
薬：Placebo
Identical matching placebo
アクティブコンパレータ：Apremilast 30 mg
Apremilast 30 mg by mouth (PO) twice a day (BID). Participants initially randomized to apremilast 30 mg BID, and who were able to demonstrate a Psoriasis Area Severity Index (PASI) -75 response at week 32 were randomized (1 to 1) to either apremilast 30 mg BID or oral placebo (until effect is lost). At relapse/loss of response to therapy prior to Week 52 (the time at which 75% improvement in PASI score compared to baseline was lost) or at Week 52, participants were re-treated with apremilast 30 mg BID for the duration of their participation in the study. Non-responders or partial responders (PASI response <75) received additional topical therapies or phototherapy beginning at Week 32.
薬：アプレミラスト
他の名前：
  • CC-10004
  • オテズラ
薬：Placebo
Identical matching placebo
薬：Topical treatments or phototherapy
At week 32, participants considered partial responders or non-responders had the option of adding topical therapies and/or phototherapy to their treatment regimen.
他の名前：
  • 光療法
  • Corticosteroid creams

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Percentage of Participants Who Achieved a 75% Improvement (Response) in the Psoriasis Area Severity Index (PASI-75) at Week 16 From Baseline
時間枠：Baseline to 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 is missing.
Baseline to Week 16

二次結果の測定

結果測定
メジャーの説明
時間枠
16週目のそう痒視覚アナログスケール（VAS）スコアのベースラインからの変化
時間枠：ベースラインと16週目
そう痒視覚アナログ スコア (VAS) は、参加者が経験するかゆみと不快感の量を測定するために使用されました。 かゆみ（かゆみ）に関する参加者の評価: 平均して、この 1 週間で、あなたの状態が原因でどれくらいのかゆみがありましたか? すべての VAS 値の範囲は 0 ～ 100 です。 スコアが高いほど、より深刻な症状または疾患に対応します。 ベースラインからの変化は VAS スケールで計算されました。ここで、変化 = 訪問値 - ベースライン値です。
ベースラインと16週目
Percentage of Participants Who Achieved a Static Physician Global Assessment (sPGA) Score of Clear (0) or Almost Clear (1) With At Least 2 Points Reduction From Baseline
時間枠：Baseline to Week 16
The sPGA was a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. When making the assessment of overall severity, the Investigator factored in areas that have already been cleared (ie, have scores of 0) and did not just evaluate remaining lesions for severity, ie, the severity of each sign was averaged across all areas of involvement, including cleared lesions. In the event of different severities across disease signs, the sign that is the predominant feature of the disease should be used to help determine the sPGA score.
Baseline to Week 16
Percent Change From Baseline in Percent of Affected Body Surface Area (BSA) at Week 16
時間枠：Baseline and Week 16
BSA was a measurement of involved skin. The overall BSA affected by psoriasis was estimated based on the palm area of the participant's hand (entire palmar surface or "handprint" including the fingers), which equates to approximately 1% of total body surface area. BSA percent change from baseline (Visit 2 Week 0) was determined at each visit of the study, which is calculated as 100*(visit BSA - baseline BSA) / baseline BSA (%).
Baseline and Week 16
Percent Change From Baseline in the Psoriasis Area Severity Index (PASI) Score at Week 16
時間枠：Baseline to Week 16
Psoriasis Area Severity Index (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 total qualitative score (sum of erythema, thickness, and scaling scores) is multiplied by the degree of involvement for each anatomic region and then multiplied by a constant. These values for each anatomic region are summed to yield the PASI score. The PASI score was set to missing if any severity score or degree of involvement is missing. PASI score percent change from baseline was calculated as 100* (visit score - baseline score)/baseline score (%).
Baseline to Week 16
Percentage of Participants Who Achieved a 50% Improvement (Response) in the PASI Score (PASI-50) at Week 16 From Baseline
時間枠：Baseline to Week 16
A participant was classified as having at least a 50% improvement in PASI score from baseline, which was equivalent to a percent change from baseline ranging from -100% to -50%. PASI score is based on an assessment of erythema (reddening), induration (plaque thickness), desquamation (scaling), and the percent area affected as observed on the day of examination.
Baseline to Week 16
Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16
時間枠：Baseline to Week 16
DLQI is a simple, compact, and practical questionnaire for use in a dermatology clinical setting to assess limitations related to the impact of skin disease. The instrument contains ten items dealing with the participant's 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 is derived by summing all item scores, which has a possible range of 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 the Mental Component Summary (MSC) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 at Week 16
時間枠：Baseline to Week 16
The SF-36 was a 36-item general health status instrument and 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 health. Two overall summary scores were obtained - a Physical Component Summary score (PCS) and a Mental Component Summary score (MCS). Scores from the 8 scales, PCS and MCS were transformed to the norm-based scores using weights from U.S. general population, with 50 as the average and 10 as the standard deviation, higher scores indicating better health. For norm based scores, change from baseline were calculated for the 8 scales and the two summary scales, where change = visit value - baseline value.
Baseline to Week 16
Percentage of Participants Who Achieved Both a 75% Improvement (Response) in the PASI and sPGA Score of Clear (0) or Almost Clear (1) With at Least 2 Points Reduction at Week 16 From Baseline
時間枠：Baseline to Week 16
PASI-75 response was 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. See Outcome Measure #1 for further description. sPGA is a 5-point scale ranging from 0 (clear), 1 (almost clear), 2 (mild), 3 (moderate), to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. See OCM #2 for further description.
Baseline to Week 16
Kaplan Meier Estimate of Time to Loss of PASI-75 Response (Loss of Effect) at Week 32 During the Re-Randomized Treatment Withdrawal Phase
時間枠：Week 32 to Week 52
Time to loss was the time between the re-randomization date and the date of the first assessment where loss of PASI-75 was observed (event); or the time between the re-randomization date and the date of the last PASI assessment in the Weeks 32-52 interval prior to addition of protocol-prohibited medication/therapy, or resumption of APR 30 BID, or discontinuation, or Week 52 if no loss (censored).
Week 32 to Week 52
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the Placebo-Controlled Phase
時間枠：Week 0 to Week 16; mean duration of exposure was 14.8 weeks and 15.0 weeks for subjects randomized to placebo and apremilast respectively.
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.
Week 0 to Week 16; mean duration of exposure was 14.8 weeks and 15.0 weeks for subjects randomized to placebo and apremilast respectively.
Number of Participants With TEAEs During the Apremilast-Exposure Period Through Week 260
時間枠：Week 0 to Week 260; mean exposure to apremilast 30 mg BID during the Apremilast-exposure Period up to Week 260 was 97.83 weeks
The Apremilast-exposure Period started on the date of the first dose of apremilast (Week 0 for participants originally randomized to apremilast or Week 16 for participants originally randomized to placebo) to the last dose of apremilast. Adverse events that started after 28 days of initiating placebo and before resuming apremilast treatment in the Randomized Treatment Withdrawal Phase (Weeks 32 to 52) were excluded in the Apremilast-exposure Period. 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.
Week 0 to Week 260; mean exposure to apremilast 30 mg BID during the Apremilast-exposure Period up to Week 260 was 97.83 weeks
Number of Participants With a Psoriasis Flare or Rebound During the Placebo-Controlled Phase
時間枠：Weeks 0 to Week 16
Psoriasis flare was defined as a sudden intensification of psoriasis requiring medical intervention, or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. Note categories below. [1] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis) started on or after the first dose date and on or before the last dose date within the phase. [2] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis, Rebound psoriasis) started after the last dose date for participants who discontinued within the phase. [3] PASI >= 125% of baseline score at any visit after the last dose date for participants who discontinued within the phase and were not included in [1] and/or [2].
Weeks 0 to Week 16
Number of Participants With a Psoriasis Flare or Rebound During the During the Apremilast-exposure Period Through Week 260
時間枠：Week 0 to Week 260
Psoriasis flare was defined as a sudden intensification of psoriasis requiring medical intervention, or a diagnosis of new generalized erythrodermic, inflammatory, or pustular psoriasis. Rebound is defined as a severe and sudden worsening of disease that occurs after treatment has been discontinued. Note categories below. [1] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis) started on or after the first dose date and on or before the last dose date within the phase. [2] Psoriasis adverse events (ie, preferred term as Guttate psoriasis, Psoriasis, Pustular psoriasis, Rebound psoriasis) started after the last dose date for participants who discontinued within the phase. [3] PASI >= 125% of baseline score at any visit after the last dose date for participants who discontinued within the phase and were not included in [1] and/or [2].
Week 0 to Week 260

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Amgen

出版物と役立つリンク

研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。

一般刊行物

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2010年9月9日

一次修了 (実際)

2012年2月23日

研究の完了 (実際)

2016年11月22日

試験登録日

最初に提出

2010年8月31日

QC基準を満たした最初の提出物

2010年9月1日

最初の投稿 (見積もり)

2010年9月2日

学習記録の更新

投稿された最後の更新 (実際)

2022年3月15日

QC基準を満たした最後の更新が送信されました

2022年3月3日

最終確認日

2020年4月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • CC-10004-PSOR-008

この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。

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