Efficacy of Ustekinumab Followed by Abatacept for the Treatment of Psoriasis Vulgaris (PAUSE)
2018年12月26日 更新者：National Institute of Allergy and Infectious Diseases (NIAID)
Efficacy of Ustekinumab (Anti-IL-12/23) Followed by Abatacept (CTLA4-Ig) for the Treatment of Psoriasis Vulgaris (ITN059AI)
The purpose of this study is to determine if the use of ustekinumab, followed by abatacept, will prevent relapse in people with moderate to severe plaque psoriasis.
研究概览
详细说明
Psoriasis is a chronic immune disease of the skin and joints that affects about 2% of the population. The most common form of psoriasis is plaque psoriasis, also called psoriasis vulgaris. A variety of drugs, including biologics, are available for treatment of moderate to severe psoriasis. When biologic agents are stopped, psoriasis can return (relapse) and often requires the biologic to be restarted and continued. No treatment program has been identified to prevent relapse of psoriasis.
The study design has a lead-in period of weight-based ustekinumab treatment, with all participants receiving either 45 mg ustekinumab (<= 100 kg) or 90 mg ustekinumab (> 100 kg) administered subcutaneously at weeks 0 and 4. At week 12, participants will be assessed for a Psoriasis Area and Severity Index (PASI) 75 response to ustekinumab. Participants who do not achieve a PASI 75 score will be discontinued from the investigation and permitted to seek standard therapy.
研究类型
介入性
注册 (实际的)
108
阶段
- 阶段2
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Alberta
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Calgary、Alberta、加拿大、T2G 1B1
- Kirk Barber Research
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Quebec
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Montreal、Quebec、加拿大、H2K 4L5
- Innovaderm Research Inc.
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California
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Los Angeles、California、美国、90045
- Dermatology Research Associates
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Illinois
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Chicago、Illinois、美国、60611
- Northwestern University
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Louisiana
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New Orleans、Louisiana、美国、70112
- Tulane University School of Medicine: Dept. of Dermatology
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Michigan
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Ann Arbor、Michigan、美国、48109
- University of Michigan
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New York
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New York、New York、美国、10065
- The Rockefeller University
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North Carolina
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Winston-Salem、North Carolina、美国、27104
- Wake Forest University
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Ohio
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Cleveland、Ohio、美国、44106
- Case Western University
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Utah
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Salt Lake City、Utah、美国、84132
- The University of Utah
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 65年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- A diagnosis of plaque psoriasis for at least 6 months
- Baseline Psoriasis Area and Severity Index (PASI) score >= 12
- >=10% body surface area psoriasis involvement
- Willingness to forgo other available psoriasis therapies, live vaccines, and pregnancy during the trial
- Ability and willingness to provide informed consent and comply with study requirements
Exclusion Criteria:
- Non-plaque forms of psoriasis
- Grade 2 or 3 moderate to severe psoriatic arthritis not adequately managed with non-steroidal anti-inflammatory drugs (NSAIDs)
- Myocardial infarction, unstable angina, cerebrovascular accident, or other significant cardiovascular event within the previous one year
- Chronic obstructive pulmonary disease (COPD)
- Comorbid condition that requires regular systemic corticosteroid treatment
- History of malignancy, except treated basal cell skin carcinoma
- Treated basal cell skin carcinoma within the previous 5 years
- Severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, pulmonary, cardiac, or neurological disease, or any other medical condition that, in the investigator's opinion, places the participant at risk by participating in this study
- History of recent or ongoing uncontrolled bacterial, viral, fungal, or other opportunistic infections
- Evidence of infection with Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV)
- Positive QuantiFERON-TB Gold test. Purified Protein Derivative (PPD) tuberculin test may be substituted for QuantiFERON-TB Gold test.
- Severe reaction or anaphylaxis to any human monoclonal antibody
- Any previous treatment with agents targeting Interleukin (IL)-12 or IL-23, including ustekinumab
- Any previous treatment with abatacept
- Treatment with biologic agents within previous 3 months, including adalimumab, etanercept, and infliximab
- Treatment with immunosuppressive medications, including methotrexate, cyclosporine, oral retinoids, prednisone, or phototherapy within previous 4 weeks
- Topical psoriasis treatment within previous 2 weeks, including topical corticosteroids, vitamin D analogues, retinoids, calcineurin inhibitors, salicylic acid, and coal tar
- Investigational study medication within previous 6 months
- Liver function test (aspartate aminotransferase [AST], alanine aminotransferase [ALT], or alkaline phosphatase) results that are >/= 2x the upper limit of normal (ULN).
- Serum creatinine >= 2x the ULN.
Any of the following hematologic abnormalities, confirmed by repeat test at least 1 week apart:
- White blood count <3,000/μL or >14,000/μL;
- Lymphocyte count <1,000/μL;
- Neutrophil count <1,500/μL;
- Platelet count <150,000 /μL; or
- Hemoglobin <10 g/dL.
- Females who are pregnant, lactating, planning on pregnancy during the study period, or unwilling to use FDA-approved method of birth control
- Receipt of a live vaccine (e.g., varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, and smallpox) in the 6 weeks before enrollment
- BCG (Bacillus Calmette-Guérin) vaccine one year prior to enrollment
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：四人间
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：UST, ABA/UST Placebo
Participants received 2 subcutaneous injections of open-label ustekinumab (UST) (45 mg for participants weighing <=100 kg at study entry or 90 mg for those weighing >100 kg at study entry), at Weeks 0 and 4 during the lead-in phase and were then randomized to receive blinded (masked) treatment of abatacept (ABA) (125 mg) subcutaneous injections weekly from Week 12 to 39, in addition to ustekinumab placebo subcutaneous injections at Weeks 16 and 28.
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Ustekinumab interferes with the actions of proteins, interleukin 12 (IL12) and interleukin 23 (IL23), which reduces inflammation (swelling) in the skin. Stelara™ is the trade name for ustekinumab and is approved by the U.S. Food and Drug Administration (FDA) to treat psoriasis. Dose: Participants who weigh <= 100 kg at study entry will receive 45 mg of ustekinumab. Participants who weigh > 100 kg at study entry will receive 90 mg of ustekinumab.
其他名称：
Abatacept (one form of the protein called CTLA4-Ig) interacts with the immune system, reducing the activity of T-cells and may prevent relapse. Orencia™ is the trade name for abatacept, and it is approved by the FDA to treat rheumatoid arthritis in adults. Dose: 125 mg sub-cutaneous injection
其他名称：
The abatacept treatment group will also receive subcutaneous placebo for ustekinumab (sterile normal saline) at week 16 and week 28, corresponding to the ustekinumab dosing regimen.
其他名称：
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有源比较器：UST, UST/ABA Placebo
Participants received 2 subcutaneous injections of open-label ustekinumab (UST) (45 mg for participants weighing <=100 kg at study entry or 90 mg for those weighing >100 kg at study entry), at Weeks 0 and 4 during the lead-in phase and were then randomized to receive blinded (masked) treatment of ustekinumab (45 mg if <=100 kg or 90 mg if >100 kg at study entry) subcutaneous injections at Weeks 16 and 28, in addition to abatacept (ABA) placebo subcutaneous injections weekly from Week 12 to 39.
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Ustekinumab interferes with the actions of proteins, interleukin 12 (IL12) and interleukin 23 (IL23), which reduces inflammation (swelling) in the skin. Stelara™ is the trade name for ustekinumab and is approved by the U.S. Food and Drug Administration (FDA) to treat psoriasis. Dose: Participants who weigh <= 100 kg at study entry will receive 45 mg of ustekinumab. Participants who weigh > 100 kg at study entry will receive 90 mg of ustekinumab.
其他名称：
The ustekinumab treatment group will also receive weekly subcutaneous injections of placebo for abatacept from week 12 to week 39, corresponding to the abatacept dosing regimen.
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse)
大体时间：Post-randomization (Week 12 to 88)
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The percentage of participants who experienced psoriasis relapse in the interval from Week 12 to 88. Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12.
This occurs if the participant obtains a PASI score at any evaluation during the specified time interval that is ≥ Week 12 PASI + [(Baseline PASI -Week 12 PASI)/2]).
Participants who terminated early from the study (drop-outs) were considered to have experienced relapse at time of drop-out.
PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities.
Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4).
Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score.
The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).
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Post-randomization (Week 12 to 88)
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse)
大体时间：Post-randomization (Week 12 to 88)
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The percentage of participants who experienced psoriasis relapse in the interval from Week 12 to 88. Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12 (Baseline PASI -Week 12 PASI).
Participants who terminated early from the study due to reasons other than psoriasis relapse or worsening psoriasis (drop-outs) were considered to have not experienced relapse at time of drop-out.
PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities.
Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4).
Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score.
The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).
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Post-randomization (Week 12 to 88)
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Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status)
大体时间：Post-randomization (Week 12 to 88)
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The percentage of participants who experienced psoriasis relapse in the interval from Week 12 to 88. Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12 (Baseline PASI -Week 12 PASI).
Participants who terminated early due to reasons other than psoriasis relapse or worsening psoriasis were considered to have a missing relapse status at time of drop-out and were excluded from the analyses.
PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities.
Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4).
Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score.
The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).
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Post-randomization (Week 12 to 88)
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Time to Psoriasis Relapse (Treating Drop-Outs as Relapse)
大体时间：Post-randomization (Week 12 to 88)
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Time in weeks from Week 12 to psoriasis relapse.
Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12.
This occurs if the participant obtains a PASI score at any evaluation during the specified time interval that is ≥ Week 12 PASI + [(Baseline PASI -Week 12 PASI)/2]).
Participants who terminated early from the study (drop-outs) were considered to have experienced relapse at time of drop-out.
PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities.
Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4).
Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score.
The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).
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Post-randomization (Week 12 to 88)
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Time to Psoriasis Relapse (Treating Drop-Outs as Censored)
大体时间：Post-randomization (Week 12 to 88)
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Time in weeks from Week 12 to psoriasis relapse.
Psoriasis relapse is defined as loss of ≥ 50% of the initial Psoriasis Area and Severity Index (PASI) improvement measured at Week 12.
This occurs if the participant obtains a PASI score at any evaluation during the specified time interval that is ≥ Week 12 PASI + [(Baseline PASI -Week 12 PASI)/2]).
Participants who terminated early from the study due to reasons other than psoriasis relapse or worsening psoriasis (drop-outs) were censored at the time of drop-out.
PASI is an assessment for psoriasis severity based on 4 body areas: Head and Neck, Upper Extremities, Trunk, and Lower Extremities.
Psoriasis severity within each body area is assessed for Redness (score 0-4), Thickness (score 0-4) and Scaling (score 0-4).
Scores for each body area are summed and weighted by the affected Body Surface Area (score 0-6) to produce the total score.
The score ranges from 0 (no psoriasis present) to 72 (very severe psoriasis).
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Post-randomization (Week 12 to 88)
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Percentage of Participants Who Were Cleared or Minimal in the Physician's Global Assessment (PGA)
大体时间：Week 40, Week 88
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Percentage of participants who were classified as cleared or minimal in the Physician's Global Assessment (PGA) average score at the specified post-randomization time point.
The PGA assesses the severity of the psoriasis in 3 components: induration, erythema and scaling.
Each component is given a score ranging from 0 to 5 based on the majority of the participant's psoriasis lesions, with higher scores indicating worse disease.
A PGA average score < 1.5 was classified as "cleared or minimal."
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Week 40, Week 88
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Change in Dermatology Life Quality Index (DLQI)
大体时间：Week 40, Week 88
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Change in the Dermatology Life Quality Index (DLQI) score from Week 12 to the specified post-randomization time point.
DLQI is a 10-question, participant-reported questionnaire that assesses quality of life with respect to skin conditions in the areas of symptoms and feelings, daily activities, leisure, work and school, personal relationships and treatment.
Each question measures the level of effect that the skin condition has on quality of life, and responses range from 'Not at all' (score = 0) to 'Very much' (score = 3).
The overall score is the sum of the scores for all 10 questions and ranges from 0-30, with higher scores indicating worse quality of life.
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Week 40, Week 88
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Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase)
大体时间：Lead-In Phase (Week 0 to 12)
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Number of participants who experienced adverse events (AEs) during the lead-in phase (Week 0 to 12), classified by severity and type.
AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database.
In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale.
AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol.
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Lead-In Phase (Week 0 to 12)
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Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase)
大体时间：Lead-In Phase (Week 0 to 12)
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Number of adverse events (AEs) that occurred during the lead-in phase (Week 0 to 12), classified by severity and type.
AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database.
In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale.
AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol.
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Lead-In Phase (Week 0 to 12)
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Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization)
大体时间：From randomization (Week 12) to last safety follow-up visit (up to Week 100)
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Number of participants who experienced adverse events (AEs) during the post-randomization phase (Week 12 to 100), classified by severity and type.
AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database.
In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale.
AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol.
AEs that started prior to randomization but became serious after randomization were included in the counts for the post-randomization time period.
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From randomization (Week 12) to last safety follow-up visit (up to Week 100)
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Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization)
大体时间：From randomization (Week 12) to last safety follow-up visit (up to Week 100)
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Number of adverse events (AEs) that occurred during the post-randomization phase (Week 12 to 100), classified by severity and type.
AEs were classified by grade according to the National Cancer Institute's (NCI's) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03, and all Grade 2 or greater AEs were collected in the database.
In addition, new onset or worsening psoriatic arthritis was separately collected and graded from 1 to 3 along a study-specific functional scale.
AEs were also classified based on relatedness to study drug, whether they led to study drug discontinuation, and whether they were AEs of special interest as specified in the protocol.
AEs that started prior to randomization but became serious after randomization were included in the counts for the post-randomization time period.
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From randomization (Week 12) to last safety follow-up visit (up to Week 100)
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2014年3月19日
初级完成 (实际的)
2017年12月7日
研究完成 (实际的)
2018年3月1日
研究注册日期
首次提交
2013年11月26日
首先提交符合 QC 标准的
2013年11月26日
首次发布 (估计)
2013年12月3日
研究记录更新
最后更新发布 (实际的)
2019年1月15日
上次提交的符合 QC 标准的更新
2018年12月26日
最后验证
2018年12月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
Ustekinumab的临床试验
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Centocor, Inc.完全的克罗恩病美国, 法国, 英国, 德国, 西班牙, 比利时, 以色列, 澳大利亚, 加拿大, 荷兰, 新西兰, 奥地利
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Janssen Research & Development, LLC完全的
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Janssen-Cilag Ltd.完全的克罗恩病美国, 大韩民国, 荷兰, 法国, 奥地利, 意大利, 英国, 德国, 俄罗斯联邦, 西班牙, 捷克语, 瑞典