Topical Ruxolitinib in the Treatment of Adults With Pyoderma Gangrenosum
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 12
- 主要终点
- Complete healing of target ulcer
研究概览
简要总结
This is a single-center, open-label, single-arm pilot study evaluating topical ruxolitinib (OPZELURA) as a treatment for adults with Pyoderma Gangrenosum (PG), a chronic inflammatory skin condition that causes painful ulcers. Approximately 12 participants will apply ruxolitinib cream twice daily for 24 weeks while continuing standard wound care, with the goal of determining whether the drug helps target ulcers heal completely without the need for systemic immunosuppressive therapy. Participants will be followed for a total of 28 weeks, with the option to continue treatment in a 48-week open-label extension if they respond well and remain safe on the drug. The study is sponsored by Oregon Health & Science University and funded by Incyte Corporation.
详细描述
Pyoderma Gangrenosum is a rare, ulcerative inflammatory skin condition most commonly treated with systemic corticosteroids or cyclosporine, both of which carry significant long-term toxicity risks. Topical therapy has shown effectiveness for smaller lesions, but existing topical options (corticosteroids, calcineurin inhibitors) also carry risks with prolonged use and lack robust long-term safety data. Emerging evidence implicates the JAK-STAT signaling pathway in PG pathogenesis, with JAK1/2/3 and TYK2 found to be overexpressed in PG lesions and several PG-associated inflammatory cytokines (IFN-γ, IL-6, IL-12, IL-15, IL-23) acting through JAK-STAT-dependent mechanisms. Ruxolitinib, a selective JAK1/JAK2 inhibitor already FDA-approved as a topical cream for atopic dermatitis, has not previously been studied for PG in a clinical trial; prior evidence is limited to case reports of oral JAK inhibitors used off-label for PG.
This investigator-initiated trial will enroll approximately 12 adults (ages 18-99) with a PARACELSUS score >10 and a target ulcer ≤10 cm². Participants will apply ruxolitinib cream twice daily via a Topi-Click applicator for 24 weeks, continuing standard-of-care wound care throughout (cleansing, antimicrobial and hyper-absorbent dressings, compression, and debridement as needed). No additional systemic immunosuppressive therapy will be introduced during the study, though participants may remain on a stable pre-existing dose of a biologic for an associated autoimmune comorbidity.
The study includes 10 scheduled visits over 28 weeks (Screening, Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28), with select later visits available via telemedicine for participants living more than 30 miles from OHSU. Assessments include full body skin exams with ulcer measurement, high-frequency ultrasound imaging at Weeks 0, 6, 12, and 24, blood draws for safety labs (CBC, CMP, eGFR, ESR, CRP, G6PD, lipid panel) and infectious disease screening (HIV, HBV, HCV, TB), wound fluid collection for cytokine analysis, and patient-reported outcome measures (Skindex Mini, pain NRS, PHQ-9, GAD-7).
The primary endpoint is the proportion of participants achieving complete re-epithelialization of the target ulcer at Week 24. Secondary endpoints assessed by the investigator include Physician Global Assessment (PGA) scores, percent reduction in ulcer area, time to healing, time to recurrence, and treatment failure rate; secondary endpoints assessed by the participant include quality-of-life measured by Skindex Mini and pain reduction measured by NRS. Exploratory/mechanistic endpoints include changes in pro-inflammatory cytokine and chemokine expression in blood and lesional tissue, and ultrasound-based assessment of tissue remodeling during healing.
Participants who complete the study through Week 24 with a PGA score of 1-3 and no significant safety concerns will be eligible to enroll in a 48-week open-label extension, with continued dosing for as long as clinical benefit is observed, re-evaluated annually.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willingness to comply with study procedures/requirements
- •Capable of giving informed consent
- •Diagnosis of at least one PG ulcer by clinical, histological and laboratory assessments with a maximum wound size of 10 cm
- •Male age 18-99 who agree to not father a child or donate sperm while on study and at least 1 week following last dose of the study drug. If subject is a sexually active male and could cause a pregnancy, subject must be sure that female partner(s) are using birth control that works well or not have sex.
- •Female age 18-99; either of non-childbearing potential or of childbearing potential who test negative for pregnancy and agree to use at least two reliable methods of birth control or remain abstinent during the study and for at least 1 week following the last dose of ruxolitinib.
- •Classic type of PG defined with PARACELSUS score >10
- •Are candidates for topical therapy. Subjects on existing immunosuppression for managing underlying comorbidities associated with PG will be considered for trial and allowed to continue these medications while on trial
- •Patients on potent immunosuppressants (azathioprine, cyclosporine) or Janus kinase inhibitors will not be considered in the study
- •Patients may be on stable dose of prednisone 10 mg or less
- •Undergoing at least once a week standard of care wound care at home or wound care facility.
- •Willingness to travel to OHSU for all study visits, or living >30 miles from OHSU and willing/able to participate in remote videoconferencing visits with access to a computer with internet and webcam capabilities.
排除标准
- •Patients with pyoderma gangrenosum who have more than 3 ulcers measuring total >30 cm2
- •Have history of malignancy or lymphoproliferative disease; or have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or have active primary or recurrent malignant disease; or have been in remission from clinically significant malignancy for < 5years.
- •Patients with cervical carcinoma in situ, basal cell carcinoma or squamous cell carcinomas who have had active disease within 3 years of screening for this study.
- •Active, untreated, acute or chronic infection (such as untreated tuberculosis), or immunocompromised to an extent that such that participation in the study would pose an unacceptable risk to the subject. (Treated infections such as latent tuberculosis after completion of the appropriate therapy are not excluded.)
- •Clinically serious infection or received intravenous antibiotics for an infection, within 4 weeks of randomization.
- •Active viral infection that, based on the investigator's clinical assessment, makes the subject and unsuitable candidate for the study.
- •Positive for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus.
- •Symptomatic herpes zoster infection within 12 weeks of screening or recurrent or disseminated (even a single episode) herpes zoster.
- •Symptomatic herpes simplex at the time of randomization or disseminated (even a single episode) herpes simplex
- •History of disseminated opportunistic infections (e.g., listeriosis and histoplasmosis).
- •Have a history of VTE, or are considered at high risk for VTE as deemed by the investigator, or have 2 or more of the following risk factors for VTE:
- •Aged >65 years.
- •BMI >35 kg/m
- •Oral contraceptive use and current smoker.
- •Wound care debridement of any PG ulcer within 2 weeks
- •Patients receiving regular intralesional corticosteroid treatment to manage PG or underlying comorbidities associated with PG will be allowed to continue intralesional corticosteroid treatment during screening and while on study
- •Previous exposure to a systemic JAK inhibitor (ruxolitinib, tofacitinib, upadacitinib, filgotinib) or topical JAK inhibior.
- •Clinically significant (per investigator's judgement) drug or alcohol abuse within the last 6 months preceding the Baseline Visit.
- •Had any major surgery within 8 weeks prior to baseline or will require major surgery during the study, which in the opinion of the investigator would pose an unacceptable risk to the subject.
- •Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting. Uncontrolled hypertension - confirmed systolic blood pressure >160 mmHg or diastolic blood pressure >100 mm Hg.
- •Presence of significant uncontrolled respiratory, hepatic, renal, endocrine, hematologic, neurologic, or neuropsychiatric disorders, or abnormal laboratory screening values that, in the opinion of the investigator, pose an unacceptable risk to the subject if participating in the study or of interfering with the interpretation of the data.
- •Have clinical laboratory test results at screening that are outside the normal reference range of the population and are considered clinically significant, or have any of the following specific abnormalities:
- •Neutrophil count <1500 cells/µL
- •lymphocyte count <500 cells/µL
- •platelet count <100,000 cells/µL,
- •AST or ALT > 2.5 Women who are lactating or breastfeeding.
- •Have any other condition that precludes the subject from following and completing the protocol, in the opinion of the investigator.
- •Are investigator site personnel directly affiliated with this study and/or their immediate families (spouse, parent, child, or sibling).
- •Are currently enrolled in, or discontinued from a clinical trial involving an investigational product or non-approved use of a drug or device within the last 4 weeks or a period of at least 5 half-lives of the last administration of the drug, whichever is longer, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
- •Have and/or are managing a substance use disorder involving opioids and/or cannabinoids
结局指标
主要结局
Complete healing of target ulcer
时间窗: Up to 24 weeks
The proportion of patients with complete re-epithelization, defined as 100% re-epithelialization without any drainage, of the target ulcer at week 24.
次要结局
- PGA between 0-1(Through week 24)
- Generalized Anxiety Disorder Assessment(By week 28)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(Through week 24)
- Impact of skin disease on quality of life using Skindex Mini(By week 28)
- Quality of life via Participant Global Assessment(By week 28)
- Quality of life via Participant Physical Function Assessment(By week 28)
- Patient Health Questionnaire-9(By week 28)
- Pain improvement determined by Numeric Rating Scale (NRS)(Through week 24)
- Time to healing(Through week 24)
- Time to recurrence(Through week 24)
研究者
Alex Ortega Loayza
Principal Investigator
Oregon Health and Science University