Clinical trial NCT06092216: Spesolimab in Pyoderma Gangrenosum
Official title: Characterizing Pyoderma Gangrenosum Lesion Regression and Remission by IL-36 Receptor Targeting with Spesolimab
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Pyoderma Gangrenosum
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Boehringer Ingelheim
First posted: 2023-10-23
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label study
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to assess the feasibility of using spesolimab in participants with moderate to severe pyoderma gangrenosum. Pyoderma gangrenosum is a rare, inflammatory, autoimmune condition which results in ulceration of skin. The study will also investigate the body's immune response to the spesolimab (when the body detects and defends itself against substances that appear unknown and harmful).

Detailed description: To date, there is no gold standard for treatment of PG. Patients with pyoderma gangrenosum suffer from severe pain and poor quality of life due to frequent dressing changes and disfiguring lesions. More importantly, rapidly progressing ulcers present an important risk for infection, morbidity, and mortality for patients. Spesolimab is humanized antagonistic monoclonal IgG1 antibody that blocks human IL36R signalling and subsequent downstream pro-inflammatory pathways. The IL-36 receptor blocker was recently approved for generalized pustular psoriasis (GPP). The research team hypothesize that targeting IL-36 in refractory, ulcerative postoperative PG may result in regression and resolution of a patient's lesions.

There are, at minimum, a total of 14 or 15 visits which will include physical exams, blood testing and infectious disease testing, completing questionnaires, and photographs and assessment of skin affected by PG. Spesolimab will be administered via a 90-minute infusion every 3 or 4 weeks (depending on response at Visit 4) at 8 or 9 Visits during the study.

Eligibility criteria: Inclusion Criteria:

* Male or female subjects ≥ 18 years of age at the time of signing the informed consent document
* Subject is able to understand and voluntarily sign an informed consent document prior to participation in any study assessments or procedures
* Subject is able to adhere to the study visit schedule and other protocol requirements.
* Subject has clinically diagnosed ulcerative PG with PARACELSUS score greater than or equal to 10
* Subject has at least one clinically measurable ulcerative PG lesion on body that has failed to respond to at least one prior therapy such as (but not limited to) topical corticosteroids, intralesional triamcinolone, prednisone, cyclosporine, IL-23 inhibitor, IL-17 inhibitors, IL-1 inhibitors, or TNF-α- blocker therapy
* Subject has moderate to severe PG as determined by a GPG severity score of ≥3
* Subject is judged to be in otherwise good overall health as judged by the investigator, based on medical history, limited physical examination, and laboratory testing. (NOTE: The definition of good health means a subject does not have uncontrolled significant co-morbid conditions).
* Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. While on investigational product and for at least 28 days after taking the last dose of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive options described below:

  * Option 1: Any one of the following highly effective contraceptive methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; or partner's vasectomy.
  * Or option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural \[animal\] membrane \[for example, polyurethane\]). PLUS one additional barrier method:

    * (a) diaphragm with spermicide
    * (b) cervical cap with spermicide;
    * or (c) contraceptive sponge with spermicide.

The female subject's chosen form of contraception must be effective by the time the female subject presents for her Baseline visit (for example, hormonal contraception should be initiated at least 28 days before first spesolimab infusion at Baseline).

Exclusion Criteria:

* Subject has a persistent or recurring bacterial infection requiring systemic antibiotics, or clinically significant viral or fungal or helminth parasitic infections, within 2 weeks of the Screening Visit. Any treatment of such infections must have been completed at least 2 weeks prior to the Screening Visit and no new/recurrent infections should have occurred prior to the Baseline Visit.
* Subject with current or history of positive human immunodeficiency virus (HIV), or congenital or acquired immunodeficiency (i.e. Common Variable Immunodeficiency \[CVID\]), hepatitis B or C, or active or untreated latent tuberculosis.
* Subject has clinically significant (as determined by the investigator) renal, hepatic, hematologic, intestinal, endocrine, pulmonary, cardiovascular, neurological, psychiatric, immunologic, or other major uncontrolled diseases that will affect the health of the subject during the study, or interfere with the interpretation of study results. Uncontrolled disease defined as hospitalization within 1 month of screening visit or determined by specialist (rheumatologist, gastroenterologist) consulted prior to study start.
* Subject has presence of acute demyelinating neuropathy
* Major surgery (according to the investigator's assessment) performed within 12 weeks prior to receiving first dose of spesolimab or planned during trial such as hip replacement, aneurysm removal, stomach ligation, or otherwise determined by investigator
* Subject has a suspected or active lymphoproliferative disorder or malignancy
* Subject was treated previously with spesolimab or another IL-36R inhibitor biologic
* Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treatment basal or squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix.
* Subject has received a live attenuated vaccine ≤ 30 days prior to study initiation.
* History of adverse systemic or allergic reactions to any component of the study drug.
* Female subject who is pregnant or breast feeding

Primary outcomes:
measure: Change in Global Pyoderma Gangrenosum (GPG) Severity Score
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Number of participants with Complete re-epithelization of PG lesions
timeFrame: Up to Week 28
measure: Absolute Change in patient-reported Pain severity (Pain-VAS) score
timeFrame: Baseline and up to Week 28
measure: Absolute Change in Dermatology Life Quality Index (DLQI)
timeFrame: Baseline and up to Week 28
measure: Recurrence of PG lesions (GPG >0) after achieving complete re-epithelialization (GPG score 0) and spesolimab cessation
timeFrame: Up to 16 week post-spesolimab last dose
measure: Severity of the recurrence of PG lesions - Global Pyoderma Gangrenosum (GPG) Severity Score
timeFrame: Last dose (Week 26 or 28) up to 16 week post-spesolimab last dose
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Saakshi Khattri, MD
role: PRINCIPAL_INVESTIGATOR
References: