A Multi-centre, Randomised, Placebo-controlled, Double-blind, Parallel-group Trial to Evaluate Safety and Efficacy of Spesolimab (BI 655130) in Adult Patients With Ulcerative Pyoderma Gangrenosum (PG) Who Require Systemic Therapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- LEO Pharma
- 入组人数
- 90
- 试验地点
- 135
- 主要终点
- Achievement of complete closure (PGAR-100 (100% pyoderma gangrenosum area reduction)) of the target PG ulcer at any time up to Week 26 and confirmed at the next consecutive visit (at least 2 weeks later)
研究概览
简要总结
The purpose of this study is to find out whether a medicine called spesolimab helps people with pyoderma gangrenosum (PG). The main aim is to see whether spesolimab leads to closure of PG ulcers. This study is open to adults with ulcerative PG with at least 1 ulcer that measures between 5 cm^2 to 80 cm^2 in size.
This study has 2 parts. In Part 1, participants are put into groups randomly, which means by chance. 1 group gets spesolimab and the other group gets placebo. Placebo infusions look like spesolimab infusions, but do not contain any medicine. Every participant has a 2 in 3 chance of getting spesolimab. For the first 8 weeks, participants also take corticosteroid medicine by mouth.
In Part 2, participants are put into groups again. Participants without open ulcers have an equal chance of getting spesolimab or placebo. Participants with open skin ulcers will get spesolimab.
In both parts, participants receive spesolimab or placebo as an infusion into a vein every 4 weeks.
Participants are in the study for about 1.5 years. During this time, they visit the study site 20 times. At study visits, doctors check the participant's skin for signs of PG. The doctors also regularly check participants' health and take note of any unwanted effects. The results of the groups are compared to see whether the treatment works.
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)
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
- •Adult trial participants, aged ≥18 years (if local legislation for age of consent differs, then local legislation will be followed) at screening.
- •Signed and dated written informed consent in accordance with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
- •A confirmed diagnosis of ulcerative pyoderma gangrenosum (PG) (≥10 points on the PARACELSUS score) that requires systemic therapy in the opinion of the investigator. The diagnosis needs to be confirmed by an Adjudication Committee. Trial participants with mixed PG subtypes are eligible as long as the target lesion is of the ulcerative subtype.
- •At least one measurable (defined as measuring ≥5 cm^2) PG ulcer. In trial participants with more than one PG ulcer, the target PG ulcer will be selected by the investigator and confirmed by external Adjudication Committee.
- •At the time of the Screening Visit, a maximum duration of 6 months since the target ulcer in the current PG episode was diagnosed. Target ulcers >6 months since diagnosis are allowed if they are active and progressing, as judged by the investigator and confirmed by an Adjudication Committee.
- •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 and instructions on the duration of use is provided in the participant information and in the protocol.
排除标准
- •Trial participants with non-PG lesions.
- •Trial participants with a target PG ulcer measuring >80 cm^
- •Trial participants with chronic, non-inflamed PG wounds or ulcers that are not responsive to immunosuppressive therapy, as determined by an Adjudication Committee.
- •Presence of active ulcer infection at the Screening Visit (unless treated and resolved prior to administration of the first dose of trial medication) based on investigator assessment.
- •Presence of persistent or recurring bacterial infection requiring systemic antibiotic therapy; or clinically significant viral, fungal, or parasitic infections within 2 weeks prior to the Screening Visit. Any such infection must be resolved, with treatment completed ≥2 weeks prior to the Screening Visit. No new/recurrent infections should have occurred prior to Visit
- •"Active or latent tuberculosis (TB)
- •Participants with active TB are excluded
- •Participants with latent TB may be included if treatment of latent TB, as per local guidelines, is initiated prior to randomization and completed during the course of the trial."
- •Chronic or acute infections including Human immunodeficiency virus (HIV) infections and viral hepatitis (including occult hepatitis); the corresponding laboratory tests will be performed during screening. A trial participant can be re-screened if the trial participant was treated and is cured from the acute infection.
- •Severe, progressive, or uncontrolled hepatic disease, defined as >3x Upper Limit of Normal (ULN) elevation in Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) or alkaline phosphatase, or >2x ULN elevation in total bilirubin.
- •Further exclusion criteria apply.
研究组 & 干预措施
Spesolimab
干预措施: Spesolimab (Drug)
Placebo
干预措施: Placebo matching to spesolimab (Drug)
Spesolimab
干预措施: Prednisone (Drug)
Spesolimab
干预措施: Prednisolone (Drug)
Placebo
干预措施: Prednisone (Drug)
Placebo
干预措施: Prednisolone (Drug)
结局指标
主要结局
Achievement of complete closure (PGAR-100 (100% pyoderma gangrenosum area reduction)) of the target PG ulcer at any time up to Week 26 and confirmed at the next consecutive visit (at least 2 weeks later)
时间窗: Up to Week 28.
PGAR-100 is defined as complete closure and re-epithelisation of a PG ulcer without drainage and requirements for dressing.
次要结局
- Key secondary endpoint: Achievement of PGAR-100 of the target PG ulcer at Week 26 confirmed at the next consecutive visit (at least 2 weeks later)(Up to Week 28.)
- Achievement of 50% area reduction (PGAR-50) of the target PG ulcer at any time up to Week 26(Up to Week 26.)
- Achievement of ≥ 3 point reduction in NRS Pain score from baseline at Week 26(At baseline and at Week 26.)
- Achievement of a DLQI of ≤ 5 at Week 26(At Week 26.)
- Achievement of complete response(At Week 26.)
- Achievement of PGAR-100 of any measurable PG ulcer (≥5 cm^2 at baseline) at any time up to Week 26 and confirmed at the next consecutive visit (at least 2 weeks later)(Up to Week 28.)
- Achievement of PGAR-100 of all measurable PG ulcers (≥5 cm^2 at baseline) at any time up to Week 26 and confirmed at the next consecutive visit (at least 2 weeks later)(Up to Week 28.)
- Time to recurrence among trial participants who had achieved CR at Week 26 up to Week 52(Up to Week 52.)
- Key secondary endpoint: Achievement of PGAR-100 of the target PG ulcer at Week 26 confirmed at the next consecutive visit (at least 2 weeks later)(Up to Week 28.)
- Achievement of 50% area reduction (PGAR-50) of the target PG ulcer at any time up to Week 26(Up to Week 26.)
- Achievement of ≥ 3 point reduction in NRS Pain score from baseline at Week 26(At baseline and at Week 26.)
- Achievement of a DLQI of ≤ 5 at Week 26(At Week 26.)
- Achievement of complete response(At Week 26.)
- Achievement of PGAR-100 of any measurable PG ulcer (≥5 cm^2 at baseline) at any time up to Week 26 and confirmed at the next consecutive visit (at least 2 weeks later)(Up to Week 28.)
- Achievement of PGAR-100 of all measurable PG ulcers (≥5 cm^2 at baseline) at any time up to Week 26 and confirmed at the next consecutive visit (at least 2 weeks later)(Up to Week 28.)
- Time to recurrence among trial participants who had achieved CR at Week 26 up to Week 52(Up to Week 52.)