A Phase 3B, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Double-Dummy, Study Of The Efficacy And Safety Of Apremilast (CC-10004), Etanercept, And Placebo, In Subjects With Moderate To Severe Plaque Psoriasis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 250
- 试验地点
- 82
- 主要终点
- Percentage of Participants Who Achieved a 75% Improvement (Response) in the Psoriasis Area Severity Index (PASI-75) for the Comparison Between Apremilast and Placebo at Week 16 From Baseline
研究概览
简要总结
This study will test the clinical effectiveness and safety of apremilast compared with placebo as well as etanercept compared with placebo in the same group of patients with moderate to severe plaque psoriasis.
详细描述
This is a phase 3b, multicenter, randomized, placebo-controlled, double-blind, double-dummy, study of the efficacy and safety of apremilast, etanercept, and placebo, in adults with moderate to severe plaque psoriasis.
250 participants will be randomized 1:1:1 to the three treatment groups. All subjects will receive both tablets and injections through Week 16.
The study will consist of four phases:
- Screening Phase - up to 35 days
- Double-blind Placebo-controlled Phase - Weeks 0-16
- Apremilast Extension Phase - Weeks 16-104
- Post-treatment Observational Follow-up Phase
During the double-blind, placebo-controlled phase, subjects will receive treatment with one of the following:
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females, ≥ 18 years of age
- •Diagnosis of chronic, moderate to severe plaque psoriasis for at least 12 months prior to Screening, and a candidate for phototherapy and/or systemic (including etanercept) therapy
- •Had an inadequate response, intolerance, or contraindication to at least 1 conventional systemic agent for the treatment of psoriasis.
- •No prior exposure to biologics for treatment of psoriatic arthritis or psoriasis
排除标准
- •Other than psoriasis, history of any clinically significant and uncontrolled systemic diseases; any condition, including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if he/she were to participate in the study.
- •Pregnant or breast feeding.
- •Have failed more than 3 systemic agents for treatment of psoriasis.
- •History of allergy to any component of the investigational product (IP), including human immunoglobulin (Ig) proteins or allergy to etanercept.
- •Hepatitis B surface antigen or anti-hepatitis C antibody positive at Screening.
- •Latent, active tuberculosis (TB) or inadequately treated TB; nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis, Clostridium difficile).
- •Have a history of, or ongoing, chronic or recurrent infectious disease
- •Have received, or are expected to receive, any live virus or bacterial vaccination within 3 months before first administration of IP, or through Week 20 during the study.
- •Had a Bacillus Calmette-Guérin (BCG) vaccination within 1 year prior to screening.
- •History of positive human immunodeficiency virus (HIV), or have congenital or acquired immunodeficiency (eg, common variable immunodeficiency disease).
- •Active substance abuse or a history of substance abuse within 6 months prior to Screening.
- •Malignancy or history of malignancy, except for treated [ie, cured] basal cell or squamous cell in situ skin carcinomas and cervical intraepithelial neoplasia [CIN] or carcinoma in situ of the cervix with no evidence of recurrence within the previous 5 years.
- •Psoriasis flare or rebound within 4 weeks prior to Screening.
- •Topical therapy within 2 weeks of randomization or systemic therapy for psoriasis within 4 weeks prior to randomization
- •Use of phototherapy within 4 weeks prior to randomization or prolonged sun exposure or use of tanning booths or other ultraviolet (UV) light sources.
- •Any investigational drug within 4 weeks prior to randomization, or 5 pharmacokinetic/pharmacodynamic half lives, if known (whichever is longer).
- •Prior treatment with apremilast or etanercept.
研究组 & 干预措施
Oral placebo tablets plus SC placebo injections
Identically matching placebo tablets and evaluator/subject-blinded SC injections
干预措施: Placebo tablet (Drug)
Etanercept 50 mg plus placebo tablet
Etanercept 50 mg evaluator/subject-blinded SC QW injections plus placebo tablets orally BID
干预措施: Placebo tablet (Drug)
Apremilast 30 mg plus placebo injection
Apremilast 30 mg tablets orally twice a day (BID) plus once weekly (QW) evaluator/subject-blinded subcutaneous (SC) saline (placebo) injections
干预措施: Apremilast (Drug)
Apremilast 30 mg plus placebo injection
Apremilast 30 mg tablets orally twice a day (BID) plus once weekly (QW) evaluator/subject-blinded subcutaneous (SC) saline (placebo) injections
干预措施: Placebo injection (Drug)
Etanercept 50 mg plus placebo tablet
Etanercept 50 mg evaluator/subject-blinded SC QW injections plus placebo tablets orally BID
干预措施: Etanercept (Drug)
Oral placebo tablets plus SC placebo injections
Identically matching placebo tablets and evaluator/subject-blinded SC injections
干预措施: Placebo injection (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved a 75% Improvement (Response) in the Psoriasis Area Severity Index (PASI-75) for the Comparison Between Apremilast and Placebo at Week 16 From Baseline
时间窗: 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 was missing.
次要结局
- Percentage of Participants Who Achieved a 75% Improvement (Response) in the Psoriasis Area and Severity Index (PASI) for the Comparison Between Etanercept 50mg SC QW and Placebo at Week 16(Baseline and Week 16)
- 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 for Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16(Baseline and Week 16)
- Percent Change From Baseline in the Affected Body Surface Area (BSA) for Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16(Baseline to Week 16)
- Percentage of Participants Who Achieved a 50% Improvement (Response) in the Psoriasis Area Severity Index (PASI-50) for Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16(Baseline to Week 16)
- Change From Baseline in Dermatology Life Quality Index (DLQI) Total Score In Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16(Baseline to Week 16)
- Change From Baseline in the Mental Component Summary (MCS) Score of the Medical Outcome Study Short Form 36-item (SF-36) Health Survey Version 2.0 in Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16(Baseline to Week 16)
- Percentage of Participants Who Achieved a Lattice System Physician's Global Assessment (LS-PGA) Score of Clear (0) or Almost Clear at Week 16 in Comparison Between Apremilast and Placebo and Etanercept and Placebo at Week 16(Baseline to Week 16)
- Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Placebo-Controlled Phase(Week 0 to Week 16; mean duration of exposure was 14.90 weeks for placebo group, 15.13 weeks for apremilast group and 15.87 weeks for Etanercept group)
- Number of Participants With Treatment Emergent Adverse Events (TEAE) During the Apremilast-exposure Period(From the first dose of apremilast (either Week 0 for participants originally randomized to apremilast or Week 16 for those originally randomized to placebo or etanercept who were switched to apremilast at week 16) until 28 days after last apremilast dose)
- Psoriasis Flare/Rebound(From the first dose of apremilast (either Week 0 or Week 16 for participants originally randomized to placebo or etanercept who were switched at Week 16) until 28 days after the last dose of apremilast.)