EvasayilTM : A Placebo-controlled Trial to Evaluate the Efficacy and Safety of Spesolimab in the Treatment of Patients With Netherton Syndrome
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 43
- 试验地点
- 41
- 主要终点
- IASI Response, Defined as a Decrease of at Least 50% Absolute Change in IASI Score From Baseline at Week 16 (Yes/No)
研究概览
简要总结
This study is open to people with a skin disease called Netherton syndrome (NS). People can join the study if they are 12 years or older. The purpose of this study is to find out whether a medicine called spesolimab helps people with NS.
Participants are divided into a spesolimab and a placebo group. Placebo injections look like spesolimab injections but do not contain any medicine. Every participant has a 2 in 3 chance of being in the spesolimab group. In the beginning, participants get the study medicine as an injection into a vein. Afterwards, they get it as an injection under the skin every month.
After 4 months, participants in the placebo group switch to spesolimab treatment.
Participants are in the study for up to 3 years. During this time, they visit the study site up to 42 times. The doctors regularly check participants' NS symptoms. The results are compared between the groups to see whether spesolimab works. The doctors also regularly check participants' general health and take note of any unwanted effects.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients, aged 12 years and older (weight minimum is 35kg).
- •Confirmed diagnosis of Netherton syndrome (NS) (causative SPINK5 mutations) at baseline (Visit 2).
- •At least moderate severity of erythema at baseline (visit 2) (Ichthyosis Area Severity Index (IASI) score ≥ 16 and IASI-Erythema (E) score ≥8) and ≥ 3 on Investigator Global Assessment (IGA) score.
- •Signed and dated written informed consent and assent in accordance with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission in the trial
- •Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the clinical trial protocol (CTP) as well as in the patient, parent(s) (or patient's legal guardian) information.
排除标准
- •Patients who have used topical corticosteroids (medium to high, US class I-V), topical retinoids, topical calcineurin inhibitors or keratolytics within 1 week prior to randomisation
- •Patients who have used emollient on the area to be biopsied in the previous 24 hours
- •Patients who have used systemic retinoids, other systemic immunosuppressants, systemic corticosteroids or phototherapy within 4 weeks prior to randomisation
- •Patients who have used systemic antibiotics within 2 weeks prior to randomisation
- •Patients who have received live vaccines within 4 weeks prior to randomisation
- •Patients who have received investigational products, biologics or immunoglobulins within 4 weeks or 5 half-lives (whichever is longer) prior to randomisation
- •Severe, progressive, or uncontrolled hepatic disease, defined as >3-fold Upper Limit of Normal (ULN) elevation in Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) or alkaline phosphatase, or >2-fold ULN elevation in total bilirubin
- •Patients who have any prior exposure to BI 655130 or another interleukin 36 receptor (IL-36R) inhibitor biologics
- •Further exclusion criteria apply
研究组 & 干预措施
Placebo
干预措施: Spesolimab - solution for infusion (Drug)
Placebo
干预措施: Placebo matching to spesolimab - solution for infusion (Drug)
Placebo
干预措施: Spesolimab - solution for injection (Drug)
Placebo
干预措施: Placebo matching to spesolimab - solution for injection (Drug)
Spesolimab
干预措施: Spesolimab - solution for infusion (Drug)
Spesolimab
干预措施: Placebo matching to spesolimab - solution for infusion (Drug)
Spesolimab
干预措施: Spesolimab - solution for injection (Drug)
结局指标
主要结局
IASI Response, Defined as a Decrease of at Least 50% Absolute Change in IASI Score From Baseline at Week 16 (Yes/No)
时间窗: At baseline and at Week 16.
Proportion of participants with an Ichthyosis Area Severity Index (IASI) response at Week 16 is reported. IASI response was defined as a decrease of at least 50% absolute change in IASI score from baseline at Week 16. Proportions were rounded to 3 decimal places. IASI is a composite score based on the global Congenital Ichthyosis Severity Instrument (CISI) score that captures differences in severity in different body regions as a function of their body surface area, and also standardizes the number of choices within the Likert scales for erythema and scaling. The score ranges from 0-48 (sum of a max score of 24 for erythema and 24 for scaling). A higher score means worse clinical severity. 95% confidence intervals (CI) are calculated using the method of Wilson.
次要结局
- Key Secondary Endpoint: IGA Response, Defined as a Decrease of at Least 1-grade Absolute Change in IGA Score From Baseline at Week 16 (Yes/No)(Baseline and at Week 16 after start of study treatment administration.)
- IGA Score of 0 or 1 at Weeks 4, 8, 12 and 16 (Yes/No)(At Week 4, at Week 8, at Week 12, at Week 16 after start of study treatment administration.)
- Absolute Change From Baseline in NRS Itch at Weeks 4, 8, 12 and 16(MMRM model included measurements from baseline and Week 4, 8, 12, 16, 20, 24, 28, 32, 40, 52, 64 after study treatment administration. MMRM values of absolute change from baseline in NRS itch at Week 4, 8, 12, 16 are presented.)
- IASI Response, Defined as a Decrease of at Least 50% Absolute Change in IASI Score From Baseline at Weeks 4, 8, and 12 (Yes/No)(At baseline and at Week 4, at Week 8, at Week 12 after start of study treatment administration.)
- IASI-E Subscore Response, Defined as a Decrease of at Least 50% Absolute Change in IASI-E Subscore at Weeks 4, 8, 12, and 16 (Yes/No)(At baseline and at Week 4, at Week 8, at Week 12, at Week 16 after start of study treatment administration.)
- IASI-S Subscore Response, Defined as a Decrease of at Least 50% Absolute Change in IASI-S Subscore From Baseline at Weeks 4, 8, 12, and 16 (Yes/No)(At baseline and at Week 4, at Week 8, at Week 12, at Week 16 after start of study treatment administration.)
- Percent Change From Baseline in IASI Score at Weeks 4, 8, 12 and 16(MMRM model included measurements from baseline and Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 60, 68 after study treatment administration. MMRM values of percent change from baseline at Week 4, 8, 12, 16 are presented.)
- Absolute Change From Baseline in NRS Pain at Weeks 4, 8, 12 and 16(MMRM model included measurements from baseline and Week 4, 8, 12, 16, 20, 24, 28, 32, 40, 52, 64 after study treatment administration. MMRM values of absolute change from baseline in NRS pain at Week 4, 8, 12, 16 are presented.)
- Absolute Change From Baseline in DLQI Score at Weeks 8 and 16(MMRM model included measurements from baseline and Week 8, 16, 24, 32, 52, after study treatment administration. MMRM values of absolute change from baseline in DLQI score at Week 8, 16 are presented.)
- Absolute Change From Baseline in CDLQI Score at Weeks 8 and 16(At baseline and at Week 8 and at Week 16 after study treatment administration.)
- The Occurrence of Treatment Emergent Adverse Events Including Serious and/or Opportunistic Infections(From first study treatment administration until end of randomised period (Week 16) plus 16 weeks of residual effect period, up to 32 weeks.)