JAK/STAT Inhibition in CNS Kohlmeier-Degos Disease
Single Patient Study of JAK/STAT Inhibition in CNS Kohlmeier-Degos Disease
Background:
Kohlmeier-Degos (K-D) is a rare disease that leads to the inflammation and/or blockage of small blood vessels in many organs; these can include the skin, eyes (rare), small bowels, lungs, heart, and the brain and spinal cord (central nervous system, or CNS). There are no known effective treatments for K-D that affects the CNS.
Objective:
To test a drug (ruxolitinib) in a person with K-D affecting the CNS.
Eligibility:
This study is designed to treat 1 adult participant with K-D affecting the CNS.
Design:
The participant will be screened:
They will have a physical exam and blood tests.
They will have skin biopsies: Small samples of skin will be removed.
They will have a lumbar puncture: A needle will be inserted in his back to draw fluid from the space around the spinal cord.
They will have a magnetic resonance imaging (MRI) scan: they will lie on a table that slides into a tube to take pictures of their brain and spinal cord.
They will see a doctor who specializes in nerves.
Ruxolitinib is a tablet taken by mouth. The participant will take the drug twice a day for up to 26 weeks. The dosage may change over time.
The participant will have up to 7 clinic visits in 28 weeks. Each visit will be 1 to 3 days. MRI scans, biopsies, lumbar punctures, and other blood tests will be repeated on different visits. The participant may receive follow-up phone calls between visits. The participant will report any adverse effects. Unscheduled visits may be needed if new symptoms develop.
The last follow-up will be 4 weeks after the last dose of the study drug.
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Description:
This single patient protocol will provide off-label treatment with a JAK/STAT ( Janus kinases/ Signal transducer and Activator of Transcription proteins) inhibitor to a patient with Kohlmeier Degos disease (K-D) with neurologic involvement. We hypothesize that ruxolitinib, which targets type I IFN (Interferons ) and IFN-gamma signaling, will attenuate various neurological manifestations of K-D that are observed clinically, radiologically or in abnormal laboratory findings in our K-D patient. 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 the hypothesis that JAK/STAT inhibition by ruxolitinib will delay progression of neuroradiological manifestations of our one patient with neurological involvement of K-D disease.
Exploratory Objectives:
- Assess changes in immune cell proportion using single cell RNAseq (scRNA-seq) in biospecimens such as skin, cerebrospinal fluid (CSF) and blood after 13 weeks and up to 73 weeks of ruxolitinib treatment.
- Assess changes in plasma/serum cytokines levels and IFN scores as well as biomarker assays in CSF/ blood samples after 13 weeks and up to 73 weeks of ruxolitinib treatment..
- To test the hypothesis that ruxolitinib will stabilize or improve clinical neurologic exams in this patient.
Endpoints:
Primary Endpoint:
The primary endpoint is stability or regression of existing enhancing lesions or no development of new enhancing lesions in the brain and spine observed in MRI evaluation after 13 weeks and up to 73 weeks of ruloxitinib (10 mg BID) compared to pre-treatment MRI images.
Exploratory endpoints of this study are clinical and potential surrogate biomarker efficacy data, including:
- Changes in transcriptome/RNA expression determined by scRNA-seq in skin, CSF and peripheral blood mononuclear cells (PBMCs) between baseline measurements and after 13 weeks and up to 73 weeks of treatment.
- Attenuation of plasma/serum cytokine levels and IFN scores as well as biomarker assays in CSF and blood samples between the baseline visit and after 13 weeks and up to 73 weeks of treatment.
- Stability OR improvement of motor and/or sensory function on clinical neurologic exams between the baseline visit and after 13 weeks and up to 73 weeks of treatment.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Maryland
-
Bethesda, Maryland, United States, 20892
- National Institutes of Health Clinical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
- INCLUSION CRITERIA:
The study design was constructed to treat one participant with CNS Kohlmeier Degos Disease. Therefore, there are no specific inclusion criteria.
EXCLUSION CRITERIA:
- Active life-threatening infections
- Hemoglobin <7 g/dL
- Platelet counts < 50 K /mcL
- Neutropenia (ANC <0.5 x k/mcL)
- Lymphopenia (ALC <0.2 x k/mcL)
- LFTs (liver function test) > 3 x time upper limit
- eGFR/CreatCr < 30 mL/min
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Ruxolitinib in Participants with CNS Kohlmeier-Degos Disease
Ruxolitinib at 5 mg twice a day (BID) for 1 week and then at 10 mg BID for 13-73 weeks and 1 week of 5 mg BID before stopping ruxolitinib.
|
Ruxolitinib at 5 mg twice a day (BID) for 1 week and then at 10 mg BID for 13-73 weeks and 1 week of 5 mg BID before stopping ruxolitinib.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Number of Participants With Stable or no Lesions Developed Based on MRI Neurological Involvement of K-D Disease Following Ruloxitinib
Time Frame: Baseline, up to 13 weeks
|
The primary endpoint is stability or regression of existing enhancing lesions or no development of new enhancing lesions in the brain and spine observed in MRI evaluation after 13 weeks and up to 73 weeks of ruloxitinib (10 mg BID) compared to pre-treatment MRI images.
|
Baseline, up to 13 weeks
|
|
Number of Participants With Stable or no Lesions Developed Based on MRI Neurological Involvement of K-D Disease Following Ruloxitinib
Time Frame: 13 weeks up to 72 weeks
|
The primary endpoint is stability or regression of existing enhancing lesions or no development of new enhancing lesions in the brain and spine observed in MRI evaluation after 13 weeks and up to 73 weeks of ruloxitinib (10 mg BID) compared to pre-treatment MRI images.
|
13 weeks up to 72 weeks
|
Collaborators and Investigators
Investigators
- Principal Investigator: Cornelia D Cudrici, M.D., National Heart, Lung, and Blood Institute (NHLBI)
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 10001517
- 001517-H
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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