A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Explore Changes in Subcutaneous Adipose Tissue and Modulation of Skin Inflammation After 12 Weeks of Treatment With Secukinumab, Compared to Placebo, and up to 52 Weeks of Treatment With Secukinumab in Adult Patients With Moderate to Severe Plaque Psoriasis
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 102
- 试验地点
- 16
- 主要终点
- Number of and Percentage of Participants Who Achieved Psoriasis Area and Severity Index 90 (PASI 90) at Week 12
研究概览
简要总结
This study provided a comparison of secukinumab to placebo with respect to skin inflammation as measured by skin exams in comparison to skin biopsies, adipose tissue and blood sample analyses.
详细描述
This was a randomized, double-blind, placebo-controlled, multicenter design. Patients with moderate to severe plaque psoriasis received secukinumab 300 mg or placebo, with randomization stratified by body weight (< 90 kg, ≥ 90 kg). There were 5 periods to the study: Screening (1 to 4 weeks), Double-blind Treatment Period (12 weeks), Double-blind Induction Period (4 weeks), Open-label Treatment Period (36 weeks), and Follow-up Period (1 week).
During the Double-blind Treatment Period, all patients attended study visits at Baseline, Weeks 1, 2, 3, 4, 8, and 12, and all doses of study treatment were self-administered at the study site. Patients underwent lesional (LS) and non-lesional (NL) skin biopsies at Baseline and Week 12. Assessments for the primary efficacy variable were performed at Week 12 before patients received their Week 12 dose. During the Double-blind Induction Period, patients randomized to placebo were switched to secukinumab 300 mg for the remainder of the study.
K16 and skin histology/biomarkers were assessed from skin biopsies. The Psoriasis Assessment and Severity Index (PASI) and the Investigator's Global Assessment modified 2011 scale (IGA mod 2011) were performed at specified study visits. Safety was monitored by vital signs, weight, waist circumference, body mass index (BMI), and clinical laboratory tests (serum chemistry, hematology, highsensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c), homeostatic assessment of insulin resistance (HOMA-IR), viral serology, serum and urine pregnancy).
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
- •Written informed consent must be obtained before any assessment is performed
- •Clinical diagnosis of chronic plaque-type psoriasis at least 6 months prior to randomization
- •Moderate to severe plaque psoriasis as defined at baseline by:
- •≥10% Body Surface Area (BSA) involvement and
- •PASI total score of ≥12 and
- •IGA mod 2011 score of ≥3 (based on a scale of 0-4)
排除标准
- •Forms of diagnosed psoriasis other than chronic plaque psoriasis
- •Medication-induced or medication exacerbated psoriasis
- •Previous exposure to secukinumab or any other biologic drug directly targeting IL-17A or IL-17RA receptors
- •Ongoing use of prohibited treatments
- •Pregnant or nursing (lactating) women
- •Other protocol-defined inclusion/exclusion criteria may apply
结局指标
主要结局
Number of and Percentage of Participants Who Achieved Psoriasis Area and Severity Index 90 (PASI 90) at Week 12
时间窗: 12 weeks
Psoriasis Area and Severity Index 90
Number and Percentage of Participants With Response of Psoriasis Skin Lesions to Treatment at Week 12
时间窗: 12 weeks
Response in skin histology/K16 expression to treatment (answered no)
次要结局
- Change in Glucose Level From Baseline to Week 12(baseline, Week 12)
- Number of and Percentage of Participants Who Achieved Psoriasis Area and Severity Index 90 (PASI 90) at Week 52(52 weeks)
- Change in Insulin Level From Baseline to Week 12(baseline, Week 12)
- Change in Diastolic Blood Pressure From Baseline to Week 12(baseline, Week 12)
- Number and Percentage of Participants With Response of Psoriasis Skin Lesions to Treatment at Week 52(52 weeks)
- Change in Body Weight From Baseline to Week 12(baseline, Week 12)
- Change in Systolic Blood Pressure From Baseline to Week 12(baseline, Week 12)
- Change in High-sensitivity C-reactive Protein (hsCRP) From Baseline to Week 12(baseline, Week 12)
- Change in Hemoglobin A1c (HbA1c) Test for Diabetes Score From Baseline to Week 12(baseline, week 12)
- Change in Homeostatic Model Assessment of Insulin Resistance (UNIT) (HOMA-IR) From Baseline to Week 12(baseline, Week 12)