A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy and Safety Study of Two Doses of Apremilast (CC-10004) in Subjects With Active Psoriatic Arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 488
- 试验地点
- 96
- 主要终点
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16
研究概览
简要总结
The purpose of this study is to determine whether apremilast is safe and effective in the treatment of patients with psoriatic arthritis.
Apremilast is proposed to improve signs and symptoms of psoriatic arthritis (tender and swollen joints, pain, physical function) in treated patients.
详细描述
Psoriatic arthritis (PsA) is an inflammatory arthritis that occurs in 6-39% of psoriasis patients. The immunopathogenesis of PsA, which mirrors but is not identical to that seen in psoriatic plaques, reflects a complex interaction among resident dendritic, fibroblastic and endothelial cells, and inflammatory cells attracted to the synovium by cytokines and chemokines. Apremilast (CC-10004) is a novel oral agent that modulates multiple inflammatory pathways through targeted phosphodiesterase type 4 (PDE4) enzyme inhibition. Therefore, apremilast has the potential to be effective in the treatment of PsA.
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, aged ≥ 18 years at time of consent.
- •Have a diagnosis of Psoriatic Arthritis (PsA, by any criteria) of ≥ 6 months duration.
- •Meet the Classification Criteria for Psoriatic Arthritis (CASPAR) PsA at time of screening.
- •Must have been inadequately treated by disease-modifying antirheumatic drugs (DMARDs)
- •May not have axial involvement alone
- •Concurrent Treatment allowed with methotrexate, leflunomide, or sulfasalazine
- •Have ≥ 3 swollen AND ≥ 3 tender joints.
- •Males & Females must use contraception
- •Stable dose of nonsteroidal anti-inflammatory drugs (NSAIDs), narcotics and low dose oral corticosteroids allowed.
排除标准
- •Pregnant or breast feeding.
- •History of allergy to any component of the investigational product.
- •Hepatitis B surface antigen and/or Hepatitis C antibody positive at screening.
- •Therapeutic failure on > 3 agents for PsA or > 1 biologic tumor necrosis factor (TNF) blocker
研究组 & 干预措施
Apremilast 20mg
20 mg Apremilast tablets administered twice daily for 24 weeks during the placebo-controlled phase followed by 20 mg Apremilast tablets administered twice daily for up to 4.5 years in the active treatment / long-term safety phase
干预措施: Apremilast 20mg (Drug)
Apremilast 30mg
30 mg Apremilast tablets administered twice a day for 24 weeks during the placebo-controlled phase followed by 30 mg Apremilast tablets administered twice a day for up to 4.5 years in the active treatment / long-term safety phase orally twice daily
干预措施: Apremilast 30mg (Drug)
Placebo + 20 mg Apremilast
Placebo + 20 mg Apremilast tablets administered twice daily for 24 weeks during the placebo-controlled phase followed by 20 mg Apremilast tablets administered twice daily for up to 4.5 years in the active treatment / long-term safety phase. Subjects who do not have at least 20% improvement in their swollen and tender joint counts at Week 16 will escape to 20 mg Apremilast twice daily at Week 16
干预措施: Placebo + 20 mg Apremilast (Drug)
Placebo + 30 mg Apremilast
Placebo + 30 mg Apremilast tablets administered twice daily for 24 weeks during the placebo-controlled phase followed by 30 mg Apremilast tablets administered twice daily for up to 4.5 years in the active treatment / long-term safety phase. Subjects who do not have at least 20% improvement in their swollen and tender joint counts at Week 16 will escape to 30 mg Apremilast twice daily at Week 16.
干预措施: Placebo + 30 mg Apremilast (Drug)
结局指标
主要结局
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 16
时间窗: Baseline and Week 16
Percentage of participants with an ACR20 response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in 78 tender joint count; • ≥ 20% improvement in 76 swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: ◦Patient's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); ◦Patient's global assessment of disease activity (measured on a 100 mm VAS); ◦Physician's global assessment of disease activity (measured on a 100 mm VAS); ◦Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI)); ◦C-Reactive Protein.
次要结局
- Change From Baseline in Patient's Assessment of Pain at Week 16(Baseline and Week 16)
- Percentage of Participants With an ACR 20 Response at Week 24(Baseline and Week 24)
- Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 16(Baseline and Week 16)
- Change From Baseline in the Patient Assessment of Pain at Week 52(Baseline and Week 52)
- Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 16(Baseline and Week 16)
- Change From Baseline in Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 24(Baseline and Week 24)
- Change From Baseline in Dactylitis Severity Score at Week 16(Baseline and Week 16)
- Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 16(Baseline and Week 16)
- Change From Baseline in the Disease Activity Score (DAS28) at Week 16(Baseline and Week 16)
- Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 24(Baseline and Week 24)
- Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 24(Baseline and Week 24)
- Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 16(Baseline and Week 16)
- Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Response at Week 16(Baseline and Week 16)
- Percentage of Participants With MASES Improvement ≥ 20% at Week 24(Baseline and Week 24)
- Change From Baseline in the SF-36 Physical Functioning Scale Score at Week 52(Baseline and Week 52)
- Percentage of Participants With an ACR 70 Response at Week 52(Baseline and Week 52)
- Change From Baseline in 36-item Short Form Health Survey (SF-36) Physical Functioning Domain at Week 16(Baseline and Week 16)
- Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16(Baseline and Week 16)
- Change From Baseline in Patient's Assessment of Pain at Week 24(Baseline and Week 24)
- Change From Baseline in Dactylitis Severity Score at Week 24(Baseline and Week 24)
- Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24(Baseline and Week 24)
- Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 24(Baseline and Week 24)
- Percentage of Participants With a ACR 70 Response at Week 24(Baseline and Week 24)
- Percentage of Participants With a ACR 20 Response at Week 52(Baseline and Week 52)
- Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52(Baseline and Week 52)
- Percentage of Participants With a Modified Psoriatic Arthritis Response Criteria (PsARC) Response at Week 24(Baseline and Week 24)
- Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 24(Baseline and Week 24)
- Change From Baseline in the Disease Activity Score (DAS28) at Week 24(Baseline and Week 24)
- Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 16(Baseline and Week 16)
- Percentage of Participants With Good or Moderate EULAR Response at Week 24(Baseline and Week 24)
- Percentage of Participants Achieving a MASES Score of Zero at Week 24(Week 24)
- Percentage of Participants With MASES Improvement ≥ 20% at Week 52(Baseline and Week 52)
- Percentage of Participants With Dactylitis Improvement ≥ 1 Point at Week 52(Baseline and Week 52)
- Percentage of Participants With MASES Improvement ≥ 20% at Week 16(Baseline and Week 16)
- Percentage of Participants With a ACR 50 Response at Week 16(Baseline and Week 16)
- Percentage of Participants With an ACR 70 Response at Week 16(Baseline and Week 16)
- Percentage of Participants Achieving a Dactylitis Score of Zero at Week 24(Week 24)
- Percentage of Participants With a Modified PsARC Response at Week 52(Baseline and Week 52)
- Change From Baseline in Maastricht Ankylosing Spondylitis Entheses Score (MASES) at Week 52(Baseline and Week 52)
- Change From Baseline in the Dactylitis Severity Score at Week 52(Baseline and Week 52)
- Percentage of Participants Achieving a MASES Score of Zero at Week 52(Week 52)
- Percentage of Participants With an ACR 50 Response at Week 24(Baseline and Week 24)
- Percentage of Participants Achieving a MASES Score of Zero at Week 16(Week 16)
- Percentage of Participants Achieving a Dactylitis Score of Zero at Week 16(Week 16)
- Change From Baseline in the CDAI Score at Week 52(Baseline and Week 52)
- Change From Baseline in the DAS28 at Week 52(Baseline and Week 52)
- Percentage of Participants Achieving Good or Moderate EULAR Response at Week 52(Baseline and Week 52)
- Change From Baseline in the FACIT-Fatigue Scale Score at Week 52(Baseline and Week 52)
- Percentage of Participants Achieving a Dactylitis Score of Zero at Week 52(Week 52)
- Number of Participants With Treatment Emergent Adverse Events During the Placebo-Controlled Phase(Week 0 to Week 16 for placebo participants who entered EE at Week 16 and up to Week 24 for all other participants (placebo participants who remained on placebo through week 24 and participants randomized to the APR 20 mg BID or APR 30 mg BID))
- Percentage of Participants With an ACR 50 Response at Week 52(Baseline and Week 52)
- Number of Participants With TEAEs During the Apremilast-Exposure Period(Week 0 to week 260; overall median duration of exposure to apremilast 20 mg and 30 mg BID was 198 weeks)