A Phase 2a, Open-label, Proof of Concept Study to Determine the Efficacy and Safety of Etrasimod (APD334) in Patients With Pyoderma Gangrenosum
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 2
- 试验地点
- 6
- 主要终点
- Exploratory Endpoint - Change From Baseline in Dermatology Life Quality Index (DLQI) Score
研究概览
简要总结
The purpose of this Phase 2a, open label, proof-of-concept clinical study is to assess the efficacy and safety of etrasimod (APD334) in patients with Pyoderma Gangrenosum.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female (18-80 years).
- •Able to provide a signed informed consent prior to any study related procedure being conducted.
- •Diagnosis of PG with active, non-healing ulcer.
- •Considered to be in stable health in the opinion of the investigator as determined by:
- •A screening physical examination with no clinically significant abnormalities unrelated to PG.
- •Vital signs at screening: pulse rate ≥ 55 bpm, systolic blood pressure ≥ 90 mmHg, and diastolic blood pressure ≥ 55 mmHg.
- •Liver function tests (alanine aminotransferase/aspartate aminotransferase, bilirubin and alkaline phosphatase) < 2x the upper limit of normal.
- •All other pre-study clinical laboratory findings within normal range, or if outside of the normal range are not deemed clinically significant in the opinion of the investigator with exemption to leucopenia and lymphopenia - please refer to exclusion criterion
- •No clinical abnormalities noted in the12-lead electrocardiogram in the opinion of the investigator (Refer also to exclusion criterion 13).
- •No evidence of macular edema in an ophthalmology evaluation (performed by an ophthalmologist), supported with optical coherence tomography, where available (dependent on site capability) at screening.
- •Eligible male and female participants must agree not to participate in a conception process (i.e. active attempt to let female partner to become pregnant or to impregnate, sperm donation, oocyte donation, in vitro fertilization) for at least 30 days after the last dose of study drug.
- •Non-sterile participants who are sexually active must take adequate contraception measures.
排除标准
- •Clinically significant infection as judged by the investigator with an end date less than 6-weeks prior to treatment start (Day 1). In case of infection requiring hospitalization or intravenous antimicrobial therapy, or opportunistic infection, this infection must have ended at least 8 weeks prior to Day
- •Infection with hepatitis C virus anytime in the past; confirmed active infection with hepatitis B virus at screening.
- •History of severe renal or severe hepatic impairment.
- •Current active or latent tuberculosis (TB).
- •A positive diagnostic TB test at screening.
- •Exposure to B-cell or T-cell targeted therapies (such as natalizumab, rituximab, abatacept) within 5 half-lives prior to Day
- •Exposure to other immunosuppressive, immunomodulating or antineoplastic agents.
- •Receipt of any investigational agent within 30 days or 5 half lives (whichever is longer), prior to Day
- •Use of moderate to strong inhibitors of CYP2C
- •Abnormal forced expiratory volume (FEV1) or forced vital capacity (FVC).
- •Any known history of congenital or acquired immuno-deficiency.
- •Recent history (within 6 months of screening visit) of cardio- or cerebrovascular disease, acute coronary syndrome, myocardial infarction, unstable angina, cerebro-vascular accident, including transient ischemic attack.
- •History or presence of cardiac arrhythmia, conduction system disease, or use of Class Ia or Class III anti arrhythmic agents, or baseline QTc ≥ 500 msec.
- •Congestive heart failure (NYHA III or NYHA IV)
- •Any surgical procedure requiring general anesthesia within 30 days prior to Day 1 or plans to undergo major surgery during the study period.
- •History of retinal macular edema.
- •History of or signs and symptoms of progressive multifocal leukoencephalopathy (PML) as assessed by the PML checklist at screening.
- •History of more than one episode of herpes zoster or any episode of disseminated zoster.
- •Participants without documented positive varicella zoster virus (VZV) IgG antibody status or participants who have not completed VZV vaccination within 6 weeks prior to Day
- •Receipt of live vaccine within 6 weeks prior to Day
- •History of lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorder, or multiple myeloma.
- •History of malignancy except for adequately treated basal cell skin cancer and in situ carcinoma of the cervix of the uterus that have been completely excised with documented, clear margins.
- •History of severe allergic or anaphylactic reactions requiring medical attention.
- •Leukopenia or lymphopenia at screening.
- •Current or recent history (within 1 year prior to Day 1) of alcohol dependence or illicit drug use.
- •Active psychiatric problems that, in the investigator's opinion, may interfere with compliance with the study procedures.
- •History of any other clinically significant medical condition that, in the investigator's opinion, would preclude participant from safe participation in the study.
- •Inability to attend all the study visits or comply with study procedures.
- •Prior exposure to etrasimod (APD334) or prior participation in any study of etrasimod (APD334).
研究组 & 干预措施
APD334
APD334 active treatment for 12 weeks.
干预措施: APD334 (Drug)
结局指标
主要结局
Exploratory Endpoint - Change From Baseline in Dermatology Life Quality Index (DLQI) Score
时间窗: Week 12
The DLQI questionnaire assessed how much a participant's life is affected through their skin problem in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure and sport activities, work or school activities, personal relationships and treatment- related feelings. Participants responded to the 10 questions on a scale from 0 (not at all) to 3 (very much) with a total score ranging from 0 to 30. Higher scores indicated that the skin problem had an extremely large effect on the participant's life whereas lower scores indicated that the disease has minimal to no effect at all.
Exploratory Endpoint - Change From Baseline in C-reactive Protein Levels
时间窗: Week 12
Exploratory Endpoint - Assessments of Target Lesions
时间窗: Week 12
Changes in surface area
Exploratory Endpoint - Assessment of Punch Biopsies
时间窗: Week 12
Changes in histology.
Exploratory Endpoint - Change From Baseline in Physician Global Assessments for Active Skin Manifestations
时间窗: Week 12
The physician's global assessment for active skin manifestations recorded the number of ulcers, target lesion noted for endpoint evaluation, diameters of each target lesion and score of evaluation at each visit. The scores ranged from 0 (total resolution) to 4 (no evidence of healing).
Exploratory Endpoint - Change From Baseline in Patient Global Assessments for Active Skin Manifestations
时间窗: Week 12
The patient global assessment for active skin manifestation recorded the disease and pain severity using a visual analogue to mark the participant's score. Participants were asked to rate their disease severity from "not severe" to "extremely severe" and pain levels from "no pain at all' to "worst pain imaginable" in the past one week.
次要结局
未报告次要终点