Guselkumab in the Treatment of Adults With Pyoderma Gangrenosum (PG)
- Conditions
- Pyoderma GangrenosumSkin DiseasesWound HealPyodermaSkin Ulcer
- Registration Number
- NCT06563323
- Lead Sponsor
- Oregon Health and Science University
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not yet recruiting
- Sex
- All
- Target Recruitment
- 17
Inclusion Criteria:<br><br> - Willingness to comply with study procedures/requirements<br><br> - Capable of giving informed consent<br><br> - Diagnosis of at least one PG ulcer by clinical, histological and laboratory<br> assessments with a minimum wound size of 4 cm2.<br><br> - Undergoing at least once a week standard of care wound care at home or at a wound<br> care facility<br><br> - Are candidate for systemic therapy. Must be on a stable dose of prednisone of 20<br> mg/day for at least two weeks prior to first drug administration.<br><br> - Males ages 18-99 who agree to not father a child or donate sperm while on study and<br> at least 12 weeks following last dose of the study drug. If subject is sexually<br> active male and could cause pregnancy, subject much be sure that female partner(s)<br> are using birth control that works well or not have sex.<br><br> - Females ages 18-99; either of non-childbearing potential or of childbearing<br> potential who test negative for pregnancy and agree to use at least two reliable<br> methods of birth control or remain abstinent during the study for at least 12 weeks<br> following the last dose of guselkumab.<br><br> - Willingness to travel to study site for all study visits or living >30 miles from<br> study site and willing/able to participate in remote videoconferencing visits with<br> access to a computer with internet and webcam capabilities.<br><br> - Be willing to undergo perilesional and non-lesional skin biopsy at week 0 and week<br> 32 resulting in 4 biopsies during the course of the study. Participants can choose<br> if they are willing to provide 2 additional biopsies at week 16. Refusal to give<br> consent for any of the optional research samples does not exclude participant from<br> participation in the study.<br><br>Exclusion Criteria:<br><br> - Has previously received at any time any therapeutic agent directly targeted to IL-23<br> including, but not limited to, guselkumab, risankizumab, tildrakuzumab, or<br> mirikizumab<br><br> - Any drug treatment specifically for PG including but not limited to biologics (or<br> biosimilar of), experimental antibodies, small molecules and oral immunosuppressives<br> used within washout periods specified below, prior to first dose of study drug:<br><br> 1. 12 weeks for ustekinumab, ixekizumab, secukinumab, brodalumab;<br><br> 2. 8 weeks for infliximab;<br><br> 3. 6 weeks for adalimumab;<br><br> 4. 4 weeks for cyclosporine A, etanercept, inhibitors of the JAK/TYK pathway and<br> PD4 inhibitors;<br><br> 5. 2 weeks for Calcineurin inhibitor topicals (including but not limited to<br> pimecrolimus and tacrolimus) and other advanced topicals (including but not<br> limited to roflumilast and tapinarof).<br><br>If not specified specifically, a time of 4 weeks or 5 half-lives of the drug (whichever<br>is longer) prior to first drug administration.<br><br> - Intralesional corticosteroids within 4 weeks of screening.<br><br> - Active clinically infected ulcers. Individuals will be eligible for enrollment<br> following completed treatment and resolution of infection. Antibiotics for wound<br> superinfection are allowed.<br><br> - Immunomodulating medications for managing underlying comorbidities associated with<br> PG, but not PG itself (e.g., for irritable bowel disease (IBD) or rheumatoid<br> arthritis), are allowed as combination therapy except for Methotrexate (MTX) and<br> Leflunomide which are allowed individually but not in combination.<br><br> - Concurrent skin disease that is deemed to interfere with assessment of ulcer.<br><br> - Have signs or symptoms suggestive of possible lymphoproliferative disease, including<br> lymphadenopathy or splenomegaly or a history of lymphoproliferative disease within 5<br> years before screening; or currently has a known malignancy or has a history of<br> malignancy within 5 years before screening, with the exception of a nonmelanoma skin<br> cancer that has been adequately treated with no evidence of recurrence for at least<br> 3 months before the first study drug administration or cervical carcinoma in situ<br> that has been treated with no evidence of recurrence for at least 3 months before<br> the first study drug administration.<br><br> - Recent (within past 6 months) cerebrovascular accident, myocardial infarction,<br> coronary stenting. Uncontrolled hypertension - confirmed systolic blood pressure<br> >160 mmHg or diastolic blood pressure >100 mm Hg.<br><br> - Clinically significant (per investigator's judgement) drug or alcohol abuse within<br> the last 6 months preceding the Baseline Visit.<br><br> - Has not fully recovered from major surgery (e.g., requiring general anesthesia and<br> hospitalization) within 8 weeks before screening, or has such surgery planned during<br> the time the participant is expected to participate in the study (40 weeks) which in<br> the opinion of the investigator would pose an unacceptable risk to the subject.<br><br> - Presence of significant uncontrolled respiratory, hepatic, renal, endocrine,<br> hematologic, neurologic, or neuropsychiatric disorders, or abnormal laboratory<br> screening values that, in the opinion of the investigator, pose an unacceptable risk<br> to the subject if participating in the study or of interfering with the<br> interpretation of the data.<br><br> - Have clinical laboratory test results at screening that are outside the normal<br> reference range of the population and are considered clinically significant, or have<br> any of the following specific abnormalities: Neutrophil count <1500 cells/µL,<br> Lymphocyte count <500 cells/µL, Platelet count <100,000 cells/µL, AST or ALT or<br> alkaline phosphatase > 2 times the upper limit of normal, Hemoglobin <10 g/dL, Serum<br> creatinine =1.5 mg/dL (SI: =137 µmol/L), White blood cells <3500 cells/ µL<br><br> - Participant has known allergies, hypersensitivity, or intolerance to guselkumab or<br> its excipients.<br><br> - Individuals who are pregnant, lactating or breastfeeding.<br><br> - History of chronic or recurrent infections, or active, untreated, acute infection,<br> or immunocompromised to an extent that participation in the study would pose an<br> unacceptable risk to the subject based on the investigator's clinical assessment.<br><br> - Clinically serious infection or received intravenous antibiotics for an infection,<br> within 8 weeks before first dose.<br><br> - Have signs or symptoms suggestive of active Tuberculosis (TB) upon medical history<br> and/or physical examination. An exception is made for participants who are currently<br> receiving treatment or will initiate treatment for latent TB prior to first<br> administration of study intervention. For participants with a history of treated<br> latent TB there must be documentation of appropriate treatment prior to the first<br> administration of study intervention.<br><br> - Positive for human immunodeficiency virus (HIV), active hepatitis B virus, or<br> hepatitis C virus. A positive Hepatitis B surface antibody test with a corresponding<br> negative hepatitis B surface antigen test indicates immunity to the disease and will<br> not be exclusionary.<br><br> - Symptomatic herpes zoster infection within 12 weeks of screening or recurrent or<br> disseminated (even a single episode) herpes zoster.<br><br> - Symptomatic herpes simplex or disseminated (even a single episode) herpes simplex at<br> the Week 0 (baseline) visit.<br><br> - History of disseminated opportunistic
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Healing
- Secondary Outcome Measures
Name Time Method Physician Global Assessment (PGA);Decrease in ulcer area size long-term;Decrease in ulcer area size short-term;Mean decrease in ulcer area size short-term;Mean decrease in ulcer area size long-term;Skindex Mini;Skin pain scale improvement over 7 days;Skin pain scale improvement over 24 hours;Change in physical function;Mean change in global assessment score;Target ulcer remains healed;Time to recurrence;Treatment failure