NCT07767864尚未招募2 期
A Single-arm Open-label Study Assessing Efficacy of Bimekizumab in Adult Participants With Pyoderma Gangrenosum Over 24 Weeks
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Proportion of participants that achieve a PGA score of ≤ 1 at week-24.
研究概览
简要总结
The purpose of the study is to learn more about an experimental drug bimekizumab that may be helpful for Pyoderma Gangrenosum (PG). Bimekizumab will be referred to as the study drug throughout this form. The investigators are hoping to find out if bimekizumab helps in healing PG wounds. The study drug is experimental. It has been approved by the FDA for use in adults with psoriatic conditions but not for Pyoderma Gangrenosum (PG).
详细描述
This is a single-arm, open-label, interventional Phase 2 study evaluating the efficacy and safety of bimekizumab in adult participants with pyoderma gangrenosum (PG). Bimekizumab is a monoclonal antibody that inhibits IL-17A, IL-17F, and the IL-17AF heterodimer. It is FDA-approved for psoriatic conditions but is not currently approved for the treatment of PG.
Approximately 17 participants will be enrolled, with an anticipated 15 participants completing screening and initiating study treatment at Oregon Health & Science University (OHSU), accounting for an estimated 10% dropout rate.
Eligible participants will receive bimekizumab 320 mg administered subcutaneously every 2 weeks for the first 16 weeks, followed by 320 mg every 4 weeks through Week 24. Participants will be trained to self-administer study drug at home following their initial in-clinic dose, with study staff available to monitor and support self-administration at subsequent visits. All participants will also be maintained on a standardized prednisone regimen, beginning at a stable dose of 20 mg/day for at least 2 weeks prior to baseline, followed by a protocol-specified tapering schedule.
Participants will attend a total of 14 in-person study visits over 36 weeks: Screening, Week 0 (baseline), and Weeks 2, 4, 6, 8, 10, 12, 14, 16, 20, 24, 28, and 36. Study procedures conducted across these visits include vital signs, physical examination, full-body skin examination, standardized wound care, target ulcer measurement and photography, patient-reported outcome questionnaires (including pain, physical function, and mental health screening), laboratory testing, wound fluid collection, high-frequency ultrasound imaging, and periodic skin biopsy (perilesional and nonlesional) at Weeks 0, 12, and 24.
Blood and tissue samples will also be collected for exploratory biomarker and genetic/genomic analyses, including gene expression profiling and, on an optional basis, whole genome sequencing, to characterize inflammatory pathways and potential genetic contributors to PG and treatment response.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At least 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place)
- •Have a diagnosis of at least one PG ulcer defined by the investigator on the basis of results from clinical and/or histological and/or laboratory assessments: Classic PG defined as deep ulceration with undermining violaceous borders and PARACELSUS score >
- •If multiple ulcers are present, the largest ulcer (defined by greatest surface area) will be designated the target ulcer and followed throughout the study.
- •Subject has a minimum of 1 evaluable ulcer (4cm2 - 225cm2) at screening.
- •Be a candidate for systemic therapy.
- •Undergoing at least once a week wound care at home or at a wound care facility.
- •Participants must be on a stable dose of prednisone of 20 mg/day for at least two weeks prior to first drug administration (baseline) and must follow the baseline Prednisone tapering algorithm.
- •Subjects on existing immunosuppression and systemic therapies for managing underlying comorbidities associated with PG but are not intended to treat PG specifically will be included in trial and allowed to continue these medications while on trial. The comorbidity must be on a stable clinical course and clinical treatment must be stable for at least 1 month prior to screening. Dosage of medication used to treat underlying comorbidities will be documented at each visit.
- •Males ages 18 and above must agree to not father a child or donate sperm while on study and for at least 12 weeks following last dose of the study drug. A subject who is a sexually active with a woman of childbearing potential and who has not had a vasectomy must agree to use a reliable form of birth control and confirm that female partner(s) are using birth control, or remain abstinent.
- •Females ages 18 and above must be either of non-childbearing potential or of childbearing potential who test negative for pregnancy at screening, agree to urine pregnancy testing before receiving study intervention administration and agree to use at least two reliable methods of birth control or remain abstinent during the study and for at least 12 weeks following the last dose of bimekizumab Female subjects must agree to not donate eggs while on study or for 12 weeks after the last dose of bimekizumab.
- •Must sign an informed consent form (ICF) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study.
- •Be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
- •Be willing to travel to site for all study visits, and willing/able to participate in remote videoconferencing visits with access to a computer with internet and webcam capabilities.
- •Be willing to undergo perilesional and nonlesional skin biopsy at week 0 and week 24 resulting in 4 biopsies during the course of the study. Participants can choose if they are willing to provide 2 additional biopsies (perilesional and nonlesional) at week
- •Refusal to give consent for any of the optional research samples does not exclude a participant from participation in the study.
排除标准
- •Any drug treatment specifically for PG including but not limited to biologicals (or biosimilar of), experimental antibodies, small molecules and oral immunosuppressives used within washout periods specified below, prior to first dose of study drug:
- •4 weeks for any therapeutic agent directly targeted to IL-17 including, but not limited to, secukinumab, brodalumab, ixekizumab
- •8 weeks for infliximab;
- •6 weeks for adalimumab;
- •4 weeks for cyclosporine A, etanercept, inhibitors of the JAK/TYK pathway and PD4 inhibitors;
- •2 weeks for Calcineurin inhibitor topicals (including but not limited to pimecrolimus and tacrolimus) and other advanced topicals (including but not limited to roflumilast and tapinarof).
- •If not specified specifically, a time of 4 weeks or 5 half-lives of the drug (whichever is longer) prior to first drug administration.
- •Intralesional corticosteroids within 4 weeks of screening.
- •Individuals with active clinically infected ulcers. Individuals will be eligible for enrollment following completed treatment and resolution of infection. Antibiotics for wound superinfection are allowed.
- •Immunomodulating medications for managing underlying comorbidities associated with PG, but not PG itself (e.g., for rheumatoid arthritis), are allowed as combination therapy except for MTX and Leflunomide which are allowed individually but not in combination.
- •Individuals will be screened for IBD using a calprotectin test at screening. Individuals with inflammatory bowel disease (IBD) will be excluded from study.
- •Concurrent skin disease that is deemed to interfere with assessment of ulcer.
- •Have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly or a history of lymphoproliferative disease within 5 years before screening; or currently has a known malignancy or has a history of malignancy within 5 years before screening, with the exception of a nonmelanoma skin cancer that has been adequately treated with no evidence of recurrence for at least 3 months before the first study drug administration or cervical carcinoma in situ that has been treated with no evidence of recurrence for at least 3 months before the first study drug administration.
- •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.
- •Clinically significant (per investigator's judgement) drug or alcohol abuse within the last 6 months preceding the Baseline Visit.
- •Has not fully recovered from major surgery (e.g., requiring general anesthesia and hospitalization) within 8 weeks before screening, or has such surgery planned during the time the participant is expected to participate in the study (40 weeks) which in the opinion of the investigator would pose an unacceptable risk to the subject.
- •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.
- •Participants with pyoderma gangrenosum with comorbid necrotizing ulcer features or disease will be excluded from study.
- •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 or alkaline phosphatase > 2 times the upper limit of normal
- •Hemoglobin <10 g/dL
- •Serum creatinine ≥1.5 mg/dL (SI: ≤137 μmol/L)
- •White blood cells <3500 cells/ µL
- •Participant has known allergies, hypersensitivity, or intolerance to bimekizumab or its excipients (refer to Investigator's brochure)
- •Individuals who are pregnant, lactating or breastfeeding.
- •History of chronic or recurrent infections, or active, untreated, acute infection, or immunocompromised to an extent that participation in the study would pose an unacceptable risk to the subject based on the investigator's clinical assessment.
- •Clinically serious infection or received intravenous antibiotics for an infection, within 8 weeks before first dose.
- •Have signs or symptoms suggestive of active TB upon medical history and/or physical examination.
- •Have had recent close contact with a person with active TB for which a physician specializing in TB has not ruled out latent TB or has not received appropriate treatment before the first study drug administration.
- •Have a positive QuantiFERON®-TB Gold test result within 2 months before the first administration of study drug in which active TB has not been ruled out and for which appropriate treatment for latent TB has not been initiated before the first administration of study dug.
- •An exception is made for participants who are currently receiving treatment or will initiate treatment for latent TB prior to first administration of study intervention. For participants with a history of treated latent TB there must be documentation of appropriate treatment prior to the first administration of study intervention. It is the responsibility of the investigator to verify the adequacy of previous TB treatment and provide appropriate documentation. IGRA testing is not required at screening for participants with a history of treated latent TB or ongoing treatment for latent TB.
- •Positive for human immunodeficiency virus (HIV), active hepatitis B virus, or hepatitis C virus. A positive Hepatitis B surface antibody test with a corresponding negative hepatitis B surface antigen test indicates immunity to the disease and will not be exclusionary.
- •Symptomatic herpes zoster infection within 12 weeks of screening or recurrent or disseminated (even a single episode) herpes zoster.
- •Symptomatic herpes simplex or disseminated (even a single episode) herpes simplex at the Week 0 (baseline) visit.
- •History of disseminated opportunistic infections (e.g., listeriosis and histoplasmosis).
- •Have received a live vaccine within 12 weeks prior to baseline or intend to have a live vaccine during the course of the study or 4 weeks after last study drug administration or 12 weeks after last study drug administration for Bacillus Calmette-Guérin (BCG) vaccine.
- •Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (e.g., compromise the well-being) of the participant or that could prevent, limit, or confound the protocol-specified assessments.
- •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.
研究组 & 干预措施
Bimekizumab
Experimental
Will receive study drug
干预措施: Bimekizumab (Drug)
结局指标
主要结局
Proportion of participants that achieve a PGA score of ≤ 1 at week-24.
时间窗: 24 weeks
Proportion of participants that achieve a PGA score of ≤ 1 at week-24.
次要结局
- Change From Baseline in Lymphocyte and Neutrophil Migration Markers(Baseline, Week 12, Week 24)
- Change From Baseline in Ulcer Tissue Remodeling by High-Frequency Ultrasound(Baseline through Week 24)
- Time to Recurrence of Pyoderma Gangrenosum(Baseline through Week 36 (including the Week 28 recurrence follow-up visit))
- Change From Baseline in Pro-inflammatory Cytokine and Chemokine Expression(Baseline, Week 12, Week 24)
- Quality of life via Participant Global Assessment(By week 28)
- Proportion of Participants Achieving Complete Re-epithelialization of the Target Ulcer(Baseline through Week 24)
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0(Baseline through Week 36 (final safety follow-up))
- Impact of skin disease on quality of life(By week 28)
- Quality of life via Participant Physical Function Assessment(By week 28)
- Patient Health Questionnaire-9(By week 28)
- Generalized Anxiety Disorder Assessment(By week 28)
- Change From Baseline in Average Pain Numeric Rating Scale (NRS) Score(Baseline through Week 24)
- Change From Baseline in Peak Pain Numeric Rating Scale (NRS) Score(Baseline through Week 24)
- Time to Complete Healing of the Target Ulcer(Baseline through Week 36)
研究者
Alex Ortega Loayza
Principal Investigator
Oregon Health and Science University
研究点 (1)
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