A Randomized, Double-blind, Multicenter, 24-week Study of Subcutaneous Secukinumab to Assess Anti-interleukin-17A Treatment in Plaque Psoriasis Patients With Coexisting Non-alcoholic Fatty Liver Disease (pINPOINt)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 10
- 试验地点
- 9
- 主要终点
- Mean and SD Change From Baseline of PASI Score up to Week 12
研究概览
简要总结
The aim of this study was to assess the therapeutic efficacy of secukinumab on the psoriatic skin and to explore the anti-inflammatory (reduction of hepatic inflammation and cell damage), anti-steatotic (reduction of hepatic triglyceride content) and anti-fibrotic (reduction of hepatic fibrosis) effects of secukinumab in patients with psoriasis and coexisting non-alcoholic fatty liver disease (NAFLD).
详细描述
Primary outcome measure is Percentage of participants achieving ≥ 90% improvement (reduction) in PASI score compared to Baseline. Psoriasis Area and Severity Index (PASI) 90 response is defined as ≥ 90% improvement (reduction) in score compared to Baseline. It is a composite score where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. Score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. Primary analysis was planned to be performed comparing treatments with respect to the primary efficacy variable in a logistic regression model. It was planned to present the Odds Ratio and its 95%-confidence interval and p-value. Planned null hypothesis to be rejected was that the Odds Ratio of a PASI90 response for patients with secukinumab vs. patients with placebo is ≥1 after 12 weeks. Due to premature termination and limited number of treated patients with available data (7 in the secukinumab group and 3 in the placebo group), the extent of the originally planned statistical analyses of efficacy data was limited to descriptive summaries (absolute values per visit and changes from baseline; presented as mean and SD) for the score.
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
- Double (Participant, Investigator)
盲法说明
double-blind
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
- •Male/female patients, 18 years or older
- •Moderate to severe plaque-type psoriasis, candidate for systemic therapy
- •Diagnosis of NAFLD by either ultrasound at Screening or liver histology within 6 months before Baseline
- •BMI > 25 kg/ m 2
- •ALT 1.2 to 3.0 × ULN
- •MRI confirmed Liver fat ≥ 8% at Screening
排除标准
- •Forms of psoriasis other than chronic plaque-type Psoriasis
- •Drug induced psoriasis
- •Pregnant or nursing (lactating) women
- •Women of child bearing potential unless they are using effective methods of contraception
- •Ongoing use of prohibited treatments
- •Previous treatment with biological drug targeting IL-17 or the IL-17 receptor
- •Past medical history record of infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C prior to Screening
- •Unstable weight over the last 6 months prior to Screening.
- •Type I diabetes, or uncontrolled diabetes (Type I or Type II) defined as HbAlc ≥ 10% at screening.
- •Evidence of hepatic decompensation or severe liver impairment or cirrhosis
- •History of liver transplantation or planned liver transplant or biliary diversion.
- •Presence or history of other liver disease
- •Current, or history of, significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening
- •Prior or planned bariatric surgery
- •Inability or unwillingness to undergo MRI of the abdomen
- •Past medical history record of infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C prior to Screening
研究组 & 干预措施
Investigational Arm - secukinumab
secukinumab 300mg s.c. weekly in first 4 weeks, followed by q4w up to Week 20; and placebo 300mg s.c. at weeks 13, 14 and 15 to maintain the blind
干预措施: Investigational Arm - secukinumab (Biological)
Control Arm - placebo
placebo 300 mg s.c. weekly in first 4 weeks, followed by q4w up to Week 8; and secukinumab 300 mg s.c. weekly for 4 weeks starting at Week 12, followed by q4w up to Week 20
干预措施: Control Arm - placebo (Biological)
结局指标
主要结局
Mean and SD Change From Baseline of PASI Score up to Week 12
时间窗: 12 weeks
Psoriasis Area and Severity Index (PASI) 90 response is defined as ≥ 90% improvement (reduction) in score compared to Baseline. It is a composite score where 0=no symptoms, 1=slight, 2=moderate, 3=marked, 4=very marked. Score ranges from 0 to 72, where 0 indicates no psoriasis and 72 indicates very severe psoriasis. Primary analysis was planned to be performed comparing treatments with respect to the primary efficacy variable in a logistic regression model.
次要结局
- Serum Alanine Aminotransferase (ALT) Level(12 weeks)
- Mean and SD of DLQI at Week 12(12 weeks)