Treatment of Moderate-to-severe Papulopustular Rosacea with Deucravacitinib
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 33
- 试验地点
- 1
- 主要终点
- Percent change in inflammatory lesion (papule/pustule) count
研究概览
简要总结
This will be a double-blind, randomized placebo-controlled study in which participants will be randomized 2:1 to receive 6 mg deucravacitinib or placebo once daily for 8 weeks, followed by an open label extension during which all participants will receive 6 mg deucravacitinib once daily for an additional 8 weeks. The open-label extension has been incorporated in order to ensure all participants receive benefit from the study, as well as to benefit from the intra-patient comparison of placebo to drug, and to provide longer-term clinical data.
The study will include 33 adult participants with moderate-to-severe Papulopustular Rosacea (PPR). participants will have baseline Investigator Global Assessment (IGA) score of at least 3 and at least 12 inflammatory lesions.
Beginning at Baseline/Week 0 enrolled participants will receive 6mg deucravacitinib or placebo once daily for 8 weeks. At week 8, those participants originally randomized to placebo will initiate dosing with 6mg deucravacitinib once daily for 8 weeks until Week 16. Participants previously randomized to deucravacitinib will continue to receive deucravacitinib for an additional 8 weeks until Week 16. All participants will return for visits at Weeks 4, 8, 12 and 16 following study treatment initiation for repeat clinical assessments, medication reviews, tape-strip collection, blood and urine sample collections, and monitoring for adverse events.
详细描述
After providing consent, all subjects will be assessed for study eligibility, which includes a review of the subjects past and current medical conditions, familial medical history and detailed review of past and current medications. Subjects will also undergo a review of past topical treatments/therapies for PPR, and clinical assessments (inflammatory lesion count, IGA, CEA, PSA). Subjects will have urine (for urinalysis) and blood (for Complete Blood Count with differential, Comprehensive Metabolic Panel, lipid panel, creatinine kinase, C-Reactive Protein, HIV, HCV and HBV) collected for safety analysis. In addition, subjects will be screened for tuberculosis via PPD or quantiferon gold testing, and pregnancy (if applicable) via serum pregnancy test.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Male or female participants ≥ 18 years of age at the time of signing the informed consent document.
- •Participant is able to understand and voluntarily sign an informed consent document prior to participation in any study assessments or procedures.
- •Participant is able to adhere to the study visit schedule and other protocol requirements.
- •Diagnosis of PPR, baseline IGA ≥ 3, and baseline inflammatory lesion count ≥ 12
- •Participant agrees to discontinue all treatments for PPR from screening through study completion aside from the study drug
- •Participant is judged to be in otherwise good overall health as judged by the investigator, based on medical history, physical examination, and laboratory testing. (NOTE: The definition of good health means a participant does not have uncontrolled significant co-morbid conditions).
- •Participant agrees not to receive a live vaccine during the study and for at least 4 weeks after the last study drug dose.
- •Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. While on the study drug and for at least 90 days after the last dose of the study drug, male and female participants must be willing to take appropriate contraceptive measures to avoid pregnancy or fathering a child. 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 participant's chosen form of contraception must be effective by the time the female participant is enrolled into the study.
排除标准
- •The presence of any of the following will exclude a participant from enrollment:
- •Participants with other skin diseases that would interfere with the study assessment in the opinion of the investigator.
- •Active bacterial, fungal, or viral skin infection within 2 weeks from study initiation.
- •Participants has clinically significant (as determined by the investigator) renal, hepatic, hematologic, intestinal, endocrine, pulmonary, cardiovascular, neurological, psychiatric, immunologic, or other major uncontrolled diseases (e.g., malignancy, TB, HIV, HBV, HCV, thromboembolic events) that will affect the health of the participant during the study or interfere with the interpretation of study results.
- •Participant has previously received treatment with TYK2 inhibitor
- •Current topical or oral treatments (e.g., topical corticosteroids, topical calcineurin inhibitors, topical JAK inhibitors, topical metronidazole, topical minocycline, topical ivermectin, topical azelaic acid, topical brimonidine, topical oxymetazoline oral antibiotics) within 2 weeks of baseline
- •Use of systemic immunosuppressive medications, including, but not limited to, cyclosporine, systemic or intralesional corticosteroids, mycophenolate mofetil, azathioprine, methotrexate, tacrolimus within 4 weeks of study initiation
- •History of adverse systemic or allergic reactions to any component of the study drug.
- •Current participation in any other study with an investigational medication
- •Participant who is pregnant or breast feeding or plans on becoming pregnant or breastfeeding
- •Participant has received a live vaccine < 4 weeks of Baseline/Week 0 visit.
- •ANY of the following abnormalities in the clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat, if deemed necessary
- •Absolute neutrophil count of <1.2 x 109/L (<1200/mm3);
- •Hemoglobin <11.0 g/dL or hematocrit <33%;
- •Platelet count of <150 x 109/L (<150,000/mm3);
- •Absolute lymphocyte count of <0.80 x 109 /L (<800/mm3);
- •Estimated Glomerular Filtration Rate (eGFR) less than 60 mL/ml/min/1.73m2 based on CKD-Epi 2021 (creatine equation);
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values >2 times the ULN;
- •Total bilirubin ≥ 1.5 times the ULN; participants with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is ≤ ULN
研究组 & 干预措施
Placebo then Deucravacitinib
Participants receiving placebo once daily for 8 weeks. At week 8, those participants originally randomized to placebo will initiate dosing with 6mg deucravacitinib once daily for 8 weeks until Week 16.
干预措施: Placebo (Drug)
Deucravacitinib
Participants receiving 6mg deucravacitinib once daily for 8 weeks. Participants previously randomized to deucravacitinib will continue to receive deucravacitinib for an additional 8 weeks until Week 16.
干预措施: Deucravacitinib (Drug)
Placebo then Deucravacitinib
Participants receiving placebo once daily for 8 weeks. At week 8, those participants originally randomized to placebo will initiate dosing with 6mg deucravacitinib once daily for 8 weeks until Week 16.
干预措施: Deucravacitinib (Drug)
结局指标
主要结局
Percent change in inflammatory lesion (papule/pustule) count
时间窗: Baseline and Week 8
This outcome looks at the percent change in inflammatory lesion presence (papule/pustule) from Baseline and Week 8 in deucravacitinib-treated vs. placebo patients. Lesions will be physically counted.
次要结局
- Change from baseline in IGA score at 4, 8, 12, and 16 weeks(Baseline, Week 4, Week 4, Week 8, Week 12, Week 16)
- Change from baseline in The Dermatology Life Quality Index (DLQI(Baseline, Week 4, Week 4, Week 8, Week 12, Week 16)
- The Clinical Patient Severity Assessment(Baseline, Week 4, Week 4, Week 8, Week 12, Week 16)
- Frequency Adverse Events (AEs)(Baseline, Week 4, Week 4, Week 8, Week 12, Week 16)
- Investigator Global Assessment (IGA) Success(Baseline, Week 4, Week 4, Week 8, Week 12, Week 16)
- The Clinical Erythema Assessment(Week 4, Week 4, Week 8, Week 12, Week 16)
- Change from baseline in Ocular Surface Disease Index (OSDI)(Baseline, Week 4, Week 4, Week 8, Week 12, Week 16)
- Change in Inflammatory (papule/pustule) lesion count(Baseline, Week 8, Week 16)
- Percent change from baseline in IGA score at 4, 8, 12, and 16 weeks(Baseline, Week 4, Week 4, Week 8, Week 12, Week 16)
- Duration of AEs(Baseline, Week 4, Week 4, Week 8, Week 12, Week 16)
- Severity of AEs(Baseline, Week 4, Week 4, Week 8, Week 12, Week 16)
研究者
Benjamin Ungar
Assistant Professor
Icahn School of Medicine at Mount Sinai