A Phase IIa Trial of Baricitinib in the Treatment of Kohlmeier-Degos Disease Patients With Neurological Involvement
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Number of participants with stability of existing enhancing lesions in the brain and/or spine observed in MRI
研究概览
简要总结
Background:
Kohlmeier-Degos (KD) is a rare disease that causes inflammation and blood clots, leading to blockages in small blood vessels. These blockages can result in K-D lesions throughout the body, affecting the skin, lungs, heart, spinal cord, and brain. KD can be fatal. No treatment exists for this disease.
Objective:
To test a study drug (baricitinib) in people with brain and spine lesions caused by KD disease. Baricitinib is FDA approved to treat other disorders but has not yet been tried in people with KD.
Eligibility:
People aged 18 years or older with KD-related lesions in the brain and spine.
Design:
Participants will be screened; they will have a physical exam with blood tests. They will also have a baseline visit that may include multiple tests, such as imaging scans of the brain and spine; a lumbar puncture to collect fluid from the spinal canal; and a meeting with a neurologist. They will fill out a questionnaire about their health. They will continue to take their normal medications throughout the study.
Baricitinib is a tablet taken by mouth. Participants will remain on their normal medications for 12 weeks after their baseline visit. Then they will also take the study drug once a day at home for 24 weeks.
Participants will have clinic visits every few weeks for up to 40 weeks. Some visits may take 1 to 4 days. Baseline tests will be repeated 3 more times during study visits. Other visits will require only blood tests; these may be done by local labs that will send the samples to NIH; 2 visits may be done via telehealth....
详细描述
Study Description:
This phase II study will provide off-label baricitinib treatment in patients with Kohlmeier Degos disease (K-D) with neurologic involvement. We will perform a baseline research evaluation at the time of enrollment and follow each patient for 12 weeks of background therapy (defined as medications taken by the subject for management of Degos symptoms) followed by 24 weeks of baricitinib treatment (4 mg daily) in addition to background therapy followed by 4 additional weeks of background therapy with final safety assessment at 40 weeks. We will repeat research evaluations at the end of weeks 12, 24, and 36. We will compare the disease progression between weeks 1 through 12 to weeks 13 through 24 as well as weeks 13 through 36. We hypothesize that baricitinib, which targets type I interferon (IFN) and IFN-g signaling, will attenuate various neurological manifestations of K-D that are observed clinically, radiologically or in abnormal laboratory findings in our KD patients. This will help reduce IFN signaling in a manner that may slow or halt the disease progression as measured by the endpoints established below.
Objectives:
Primary Objective:
To test whether baricitinib delays progression of neuroradiological manifestations in patients with neurological involvement of K-D disease.
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
- •INCLUSION CRITERIA:
- •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- •Provision of signed and dated informed consent form by the subject or Legally Authorized Representative (LAR).
- •Stated willingness to comply with all study procedures and availability for the duration of the study.
- •Male or female, aged 18 or older.
- •Subjects diagnosed with systemic Degos disease, who manifest neurologic abnormalities observed clinically, radiologically or in abnormal laboratory findings.
- •Ability to take oral medication and be willing to adhere to the baricitinib regimen.
- •For female patients of reproductive potential, non-pregnant, non-breastfeeding: agree to use of highly effective contraception for the duration of the study and 30 days after the last dose.
- •Ability of subject or LAR to understand and the willingness to sign a written informed consent document.
排除标准
- •Active infection not responding to appropriate therapy
- •Hemoglobin <7 g/dL
- •Platelet counts < 50 K /mcL
- •Neutropenia (ANC <0.5 x k/mcL)
- •Lymphopenia (Absolute Lymphocyte Count [ALC] <0.2x k/mcL)
- •Liver function tests (LFTs > 2x time upper limit of normal)
- •Estimated Glomerular Filtration Rate (eGFR)/Creatinine (Cr < 30 mL/min)
- •Have experienced any of the following within 12 weeks of screening: VTE (DVT/pulmonary embolism [PE]), myocardial infarction (MI), unstable ischemic heart disease, stroke, or New York Heart Association Stage III/IV heart failure.
- •Have had symptomatic herpes zoster infection within 12 weeks prior to a enrolling in the study .
- •Have had household contact with a person with active TB and did not receive appropriate and documented prophylaxis for TB.
- •Have evidence of active TB or latent TB
- •Have been exposed to a live vaccine within 12 weeks of baricitinib treatment or are expected to need/receive a live vaccine during the course of the study
- •No gadolinium based contrast agent exposure is permitted if eGFR < 30 mL/min/1.73m^2 using the CKD-EPI equation measured within 5 days .
- •Breast feeding
- •Pregnancy
- •Uncontrolled malignancy
研究组 & 干预措施
Participants with K(SqrRoot)(Delta)hlmeier-Degos Disease receiving Baricitinib
All participants will take baricitinib 4mg oral daily for 24 weeks.
干预措施: Baricitinib (Drug)
结局指标
主要结局
Number of participants with stability of existing enhancing lesions in the brain and/or spine observed in MRI
时间窗: Baseline, Week 12, Week 24, Week 36
Stability of existing enhancing lesions in the brain and/or spine observed in MRI after 12 or 24 weeks of baricitinib treatment (4 mg daily) as compared to MRI images after 12 weeks of background therapy only.
Number of participants with no new enhancing lesions in the brain and/or spine observed in MRI
时间窗: Baseline, Week 12, Week 24, Week 36
Lack of development of new enhancing lesions in the brain and/or spine observed in MRI after 12 or 24 weeks of baricitinib treatment (4 mg daily) as compared to MRI images after 12 weeks of background therapy only.
次要结局
- Neurological symptoms using CTCAE(Up to 40 weeks)
- Change in health outcome questionnaire, Short Form-36 (SF-36)(Baseline, Week 12, Week 16, Week 24, Week 36, and up to Week 40)