Efficacy of Ustekinumab (Anti-IL-12/23) Followed by Abatacept (CTLA4-Ig) for the Treatment of Psoriasis Vulgaris (ITN059AI)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 108
- 试验地点
- 10
- 主要终点
- Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Ustekinumab (Biological)
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.
干预措施: Abatacept (Biological)
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.
干预措施: UST Placebo (Drug)
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.
干预措施: Ustekinumab (Biological)
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.
干预措施: ABA Placebo (Drug)
结局指标
主要结局
Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Relapse)
时间窗: Post-randomization (Week 12 to 88)
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).
次要结局
- Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as Missing Relapse Status)(Post-randomization (Week 12 to 88))
- Time to Psoriasis Relapse (Treating Drop-Outs as Censored)(Post-randomization (Week 12 to 88))
- Change in Dermatology Life Quality Index (DLQI)(Week 40, Week 88)
- Percentage of Participants Who Experienced Psoriasis Relapse (Treating Drop-Outs as No Relapse)(Post-randomization (Week 12 to 88))
- Percentage of Participants Who Were Cleared or Minimal in the Physician's Global Assessment (PGA)(Week 40, Week 88)
- Time to Psoriasis Relapse (Treating Drop-Outs as Relapse)(Post-randomization (Week 12 to 88))
- Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Lead-in Phase)(Lead-In Phase (Week 0 to 12))
- Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Lead-in Phase)(Lead-In Phase (Week 0 to 12))
- Frequency and Severity of Adverse Events and Serious Adverse Events (By Participant, Post-Randomization)(From randomization (Week 12) to last safety follow-up visit (up to Week 100))
- Frequency and Severity of Adverse Events and Serious Adverse Events (By Event, Post-Randomization)(From randomization (Week 12) to last safety follow-up visit (up to Week 100))