Pyoderma Gangrenosum
Conditions
Brief summary
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.
Interventions
DRUGSpesolimab
Solution for infusion
Placebo matching to spesolimab
DRUGPrednisone
Prednisone
DRUGPrednisolone
Prednisolone
Sponsors
LEO Pharma
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Adult trial participants, aged ≥18 years (if local legislation for age of consent differs, then local legislation will be followed) at screening. 2. 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. 3. 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. 4. 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. 5. 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. 6. 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.
Exclusion criteria
1. Trial participants with non-PG lesions. 2. Trial participants with a target PG ulcer measuring \>80 cm\^2. 3. Trial participants with chronic, non-inflamed PG wounds or ulcers that are not responsive to immunosuppressive therapy, as determined by an Adjudication Committee. 4. 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. 5. 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 2. 6. "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." 7. 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. 8. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Up to Week 28. | PGAR-100 is defined as complete closure and re-epithelisation of a PG ulcer without drainage and requirements for dressing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | PGAR-100 is defined as complete closure and re-epithelisation of a PG ulcer without drainage and requirements for dressing. |
| 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 a PGAR-50 defines an area reduction of a PG ulcer from baseline by 50%. |
| Achievement of ≥ 3 point reduction in NRS Pain score from baseline at Week 26 | At baseline and at Week 26. | Numeric Rating Scale for Pain (NRS Pain) is a unidimensional measure of pain intensity. It is a 11-point numeric scale, in which a respondent selects a whole number (0-10 integers) that best reflects the intensity of their pain, with 0 representing "no pain" and 10 representing "worst pain imaginable". Trial participant is asked to report their pain intensity in the last 24 h. |
| Achievement of a DLQI of ≤ 5 at Week 26 | At Week 26. | Dermatology Life Quality Index (DLQI) is a trial participant-administered, quality of life questionnaire consisting of 10 questions that cover 6 domains (symptoms and feelings, daily activities, leisure, work and school, personal relationships, problems with treatment). Response categories include "not relevant" or "not at all" (score of 0), "a little" (score of 1), "a lot" (score of 2) and "very much" (score of 3). Question 7 is a "yes"/ "no" question where "yes" is scored as 3. DLQI total score is calculated by summing the scores of each question, resulting in a range of 0 to 30, with higher scores indicating more impairment of a trial participant's quality of life. |
| Achievement of complete response | At Week 26. | Complete response (CR), defined as all ulcers completely closed and re- epithelised without drainage and requirements for dressing, as assessed by the investigator). |
| 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. | PGAR-100 is defined as complete closure and re-epithelisation of a PG ulcer without drainage and requirements for dressing. |
| 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. | PGAR-100 is defined as complete closure and re-epithelisation of a PG ulcer without drainage and requirements for dressing. |
| Time to recurrence among trial participants who had achieved CR at Week 26 up to Week 52 | Up to Week 52. | Recurrence is defined as emergence of the disease (PG ulcer\[s\]) at the previous ulcer sites(s) or emergence of any new PG ulcer(s). |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Finland, France, Germany, Italy, Japan, Malaysia, Norway, Poland, Portugal, Spain, Sweden, Switzerland, Taiwan, United States
Contacts
CONTACTClinical Disclosure
STUDY_DIRECTORMedical Expert
LEO Pharma
Outcome results
None listed