xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05998395</url>
    </required_header>
    <id_info>
      <org_study_id>10001517</org_study_id>
      <secondary_id>001517-H</secondary_id>
      <nct_id>NCT05998395</nct_id>
    </id_info>
    <brief_title>JAK/STAT Inhibition in CNS Kohlmeier-Degos Disease</brief_title>
    <official_title>Single Patient Study of JAK/STAT Inhibition in CNS Kohlmeier-Degos Disease</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
        <agency_class>NIH</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>National Institutes of Health Clinical Center (CC)</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Background:&#xD;
  &#xD;
        Kohlmeier-Degos (K-D) is a rare disease that leads to the blockage of small blood vessels in&#xD;
        many organs; these can include the skin, eyes, stomach, lungs, heart, and the brain and&#xD;
        spinal cord (central nervous system, or CNS). There are no known effective treatments for K-D&#xD;
        that affects the CNS.&#xD;
  &#xD;
        Objective:&#xD;
  &#xD;
        To test a drug (ruxolitinib) in a person with K-D affecting the CNS.&#xD;
  &#xD;
        Eligibility:&#xD;
  &#xD;
        This study is designed to treat 1 subject, a 58-year-old male with K-D affecting the CNS.&#xD;
  &#xD;
        Design:&#xD;
  &#xD;
        The participant will be screened:&#xD;
  &#xD;
        He will have a physical exam and blood tests.&#xD;
  &#xD;
        He will have skin biopsies: Small samples of skin will be removed.&#xD;
  &#xD;
        He will have a lumbar puncture: A needle will be inserted in his back to draw fluid from the&#xD;
        space around the spinal cord.&#xD;
  &#xD;
        He will have a magnetic resonance imaging (MRI) scan: He will lie on a table that slides into&#xD;
        a tube to take pictures of his brain and spinal cord.&#xD;
  &#xD;
        He will see a doctor who specializes in nerves.&#xD;
  &#xD;
        Ruxolitinib is a tablet taken by mouth. The participant will take the drug twice a day for up&#xD;
        to 26 weeks. The dosage may change over time.&#xD;
  &#xD;
        The participant will have up to 7 clinic visits in 28 weeks. Each visit will be 1 to 3 days.&#xD;
        MRI scans, biopsies, lumbar punctures, and other tests will be repeated on different visits.&#xD;
        The participant may receive follow-up phone calls between visits. He will report any adverse&#xD;
        effects. Unscheduled visits may be needed if new symptoms develop.&#xD;
  &#xD;
        The last follow-up will be 4 weeks after the last dose of the study drug.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Study Description: This single patient protocol will provide off-label treatment with a&#xD;
        JAK/STAT (Janus kinases/ Signal transducer and Activator of Transcription proteins) inhibitor&#xD;
        to a patient with Kohlmeier Degos disease (K-D) with neurologic involvement. We hypothesize&#xD;
        that ruxolitinib, which targets type I IFN (Interferons ) and IFN-y signaling, will attenuate&#xD;
        various neurological manifestations of K-D that are observed clinically, radiologically or in&#xD;
        abnormal laboratory findings in our K-D patient. This will help reduce IFN signaling in a&#xD;
        manner that may slow or halt the disease progression as measured by the endpoints established&#xD;
        below.&#xD;
  &#xD;
        Objectives:&#xD;
  &#xD;
        Primary Objective: To test the hypothesis that JAK/STAT inhibition by ruxolitinib will delay&#xD;
        progression of neuroradiological manifestations of our one patient with neurological&#xD;
        involvement of K-D disease.&#xD;
  &#xD;
        Exploratory Objectives:&#xD;
  &#xD;
          1. Assess changes in immune cell proportion using single cell RNAseq (scRNA-seq) in&#xD;
             biospecimens such as skin, cerebrospinal fluid (CSF )and blood after 13 weeks of&#xD;
             ruxolitinib treatment.&#xD;
  &#xD;
          2. Assess changes in plasma/serum cytokines levels and IFN scores as well as biomarker&#xD;
             assays in CSF/ blood samples after 3 weeks of ruxolitinib treatment.&#xD;
  &#xD;
          3. To test the hypothesis that ruxolitinib will stabilize or improve clinical neurologic&#xD;
             exams in this patient.&#xD;
  &#xD;
        Endpoints:&#xD;
  &#xD;
        Primary Endpoint:&#xD;
  &#xD;
        The primary endpoint is stability or regression of existing enhancing lesions or no&#xD;
        development of new enhancing lesions in the brain and spine observed in MRI evaluation after&#xD;
        13 weeks of ruloxitinib (10 mg BID) compared to pre-treatment MRI images.&#xD;
  &#xD;
        Exploratory endpoints of this study are clinical and potential surrogate biomarker efficacy&#xD;
        data, including:&#xD;
  &#xD;
          1. Changes in transcriptome/RNA expression determined by scRNA-seq in skin, CSF and&#xD;
             peripheral blood mononuclear cells (PBMCs) between baseline measurements and after 13&#xD;
             weeks of treatment.&#xD;
  &#xD;
          2. Attenuation of plasma/serum cytokine levels and IFN scores as well as biomarker assays&#xD;
             in CSF and blood samples between the baseline visit and after 13 weeks of treatment.&#xD;
  &#xD;
          3. Stability OR improvement of motor and/or sensory function on clinical neurologic exams&#xD;
             between the baseline visit and after 13 weeks of treatment.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 15, 2023</start_date>
    <completion_date type="Anticipated">March 15, 2024</completion_date>
    <primary_completion_date type="Anticipated">March 15, 2024</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>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.</measure>
      <time_frame>6 months</time_frame>
      <description>The primary endpoint is stability or regression of existing enhancing lesions or no development of new enhancing lesions the brain and spine on MRI after 13 weeks of 10 mg BID ruloxitinib treatment compared to pre-treatment images.</description>
    </primary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">1</enrollment>
    <condition>Kohlmeier Degos Disease With Neurologic Involvement</condition>
    <arm_group>
      <arm_group_label>Ruxolitinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Ruxolitinib at 5 mg twice a day (BID) for 1 week and then at 10 mg BID for 13-24 weeks and 1 week of 5 mg BID before stopping ruxolitinib.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Ruxolitinib</intervention_name>
      <description>Ruxolitinib at 5 mg twice a day (BID) for 1 week and then at 10 mg BID for 13-24 weeks and 1 week of 5 mg BID before stopping ruxolitinib.</description>
      <arm_group_label>Ruxolitinib</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          -  INCLUSION CRITERIA:&#xD;
  &#xD;
          The study design was constructed to treat one subject, a 58 year old male with CNS&#xD;
          Kohlmeier Degos Disease. Therefore, there are no specific inclusion criteria.&#xD;
  &#xD;
          EXCLUSION CRITERIA:&#xD;
  &#xD;
            -  Active life-threatening infections&#xD;
  &#xD;
            -  Hemoglobin &lt;7 g/dL&#xD;
  &#xD;
            -  Platelet counts &lt; 50 K /mcL&#xD;
  &#xD;
            -  Neutropenia (ANC &lt;0.5 x k/mcL)&#xD;
  &#xD;
            -  Lymphopenia (ALC &lt;0.2x k/mcL)&#xD;
  &#xD;
            -  LFTs (liver function test) &gt; 3x time upper limit&#xD;
  &#xD;
            -  eGFR/CreatCr &lt; 30 mL/min&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>100 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Cornelia D Cudrici, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>National Heart, Lung, and Blood Institute (NHLBI)</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Cornelia D Cudrici, M.D.</last_name>
      <phone>(301) 451-7070</phone>
      <email>cornelia.cudrici@nih.gov</email>
    </overall_contact>
    <location>
      <facility>
        <name>National Institutes of Health Clinical Center</name>
        <address>
          <city>Bethesda</city>
          <state>Maryland</state>
          <zip>20892</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>NIH Clinical Center Office of Patient Recruitment (OPR)</last_name>
        <phone>800-411-1222</phone>
        <phone_ext>TTY dial 711</phone_ext>
        <email>ccopr@nih.gov</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_001517-H.html</url>
      <description>NIH Clinical Center Detailed Web Page</description>
    </link>
    <verification_date>August 11, 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 24, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Rare Small Vessel Vasculopathy Of Unknown Etiology</keyword>
    <keyword>Kohlmeier Degos Disease With Neurologic Involvement</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Malignant Atrophic Papulosis</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05998395
  org study id: 10001517
  secondary id: 001517-H
  nct id: NCT05998395
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  Background:
  
        Kohlmeier-Degos (K-D) is a rare disease that leads to the blockage of small blood vessels in
        many organs; these can include the skin, eyes, stomach, 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 subject, a 58-year-old male with K-D affecting the CNS.
  
        Design:
  
        The participant will be screened:
  
        He will have a physical exam and blood tests.
  
        He will have skin biopsies: Small samples of skin will be removed.
  
        He will have a lumbar puncture: A needle will be inserted in his back to draw fluid from the
        space around the spinal cord.
  
        He will have a magnetic resonance imaging (MRI) scan: He will lie on a table that slides into
        a tube to take pictures of his brain and spinal cord.
  
        He 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 tests will be repeated on different visits.
        The participant may receive follow-up phone calls between visits. He 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 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-y 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:
  
          1. 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 of
             ruxolitinib treatment.
  
          2. Assess changes in plasma/serum cytokines levels and IFN scores as well as biomarker
             assays in CSF/ blood samples after 3 weeks of ruxolitinib treatment.
  
          3. 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 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:
  
          1. 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 of treatment.
  
          2. 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 of treatment.
  
          3. Stability OR improvement of motor and/or sensory function on clinical neurologic exams
             between the baseline visit and after 13 weeks of treatment.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: 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.
  time frame: 6 months
  description: The primary endpoint is stability or regression of existing enhancing lesions or no development of new enhancing lesions the brain and spine on MRI after 13 weeks of 10 mg BID ruloxitinib treatment compared to pre-treatment images.
  arm group label: Ruxolitinib
  arm group type: Experimental
  description: Ruxolitinib at 5 mg twice a day (BID) for 1 week and then at 10 mg BID for 13-24 weeks and 1 week of 5 mg BID before stopping ruxolitinib.
  intervention type: Drug
  intervention name: Ruxolitinib
  description: Ruxolitinib at 5 mg twice a day (BID) for 1 week and then at 10 mg BID for 13-24 weeks and 1 week of 5 mg BID before stopping ruxolitinib.
  arm group label: Ruxolitinib
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 100 Years
  healthy volunteers: No
  last name: Cornelia D Cudrici, M.D.
  role: Principal Investigator
  affiliation: National Heart, Lung, and Blood Institute (NHLBI)
  last name: Cornelia D Cudrici, M.D.
  phone: (301) 451-7070
  email: cornelia.cudrici@nih.gov
  facility: 
  status: Recruiting
  contact: 
  country: United States
  url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_001517-H.html
  description: NIH Clinical Center Detailed Web Page
  responsible party type: Sponsor
  mesh term: Malignant Atrophic Papulosis
  sharing ipd: Undecided