<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/NCT03233841</url>
  </required_header>
  <id_info>
    <org_study_id>RVT-801-0001</org_study_id>
    <nct_id>NCT03233841</nct_id>
  </id_info>
  <brief_title>Farber Disease Natural History Study</brief_title>
  <official_title>Observational and Cross-Sectional Cohort Study of the Natural History and Phenotypic Spectrum of Farber Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Enzyvant Therapeutics GmBH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Enzyvant Therapeutics GmBH</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to establish the natural history of Farber disease&#xD;
      (acid ceramidase deficiency) through the collection and analysis of retrospective and&#xD;
      prospective data on patients diagnosed with Farber disease. All patients diagnosed with&#xD;
      Farber disease are eligible, including both those who have and have not undergone&#xD;
      hematopoietic stem cell transplantation (HSCT). Additionally, data and records from deceased&#xD;
      patients will provide valuable retrospective data for this study.&#xD;
&#xD;
      The secondary objective of the study is to establish a set of clinical data, laboratory data&#xD;
      (biomarkers), and functional data potentially useful for:&#xD;
&#xD;
        -  Assessing the efficacy of HSCT and the efficacy of potential future therapies (for&#xD;
           example with RVT-801, recombinant human acid ceramidase) in Farber disease&#xD;
&#xD;
        -  Characterizing changes in symptoms of patients over time&#xD;
&#xD;
        -  Characterizing distinct groups (phenotypes) within the patient population&#xD;
&#xD;
        -  Documenting the disease histories of individual patients to serve as intra-subject&#xD;
           control data for those who may enroll in any future clinical studies with therapies for&#xD;
           Farber disease&#xD;
&#xD;
      The exploratory objectives of the study are:&#xD;
&#xD;
        -  To explore the relationship between patient disease activity or phenotype and specific&#xD;
           ceramide levels or specific immunologic markers (cytokines/chemokines) in blood&#xD;
&#xD;
        -  To evaluate a standardized tool, the Farber Disease Natural History Instrument (FDNI),&#xD;
           to be used for the collection of patient history information, data from clinical,&#xD;
           laboratory, genetic, and functional studies, and data from review of medical records&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 22, 2017</start_date>
  <completion_date type="Actual">December 9, 2019</completion_date>
  <primary_completion_date type="Actual">October 12, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Establish a dataset on the natural history of Farber Disease</measure>
    <time_frame>Up to 21 months</time_frame>
    <description>Collection of information for all subjects will include data from:&#xD;
Medical history&#xD;
Farber disease diagnosis, presentation, treatments and symptom progression&#xD;
Collection of information from living subjects will include:&#xD;
Medical examination&#xD;
Disease-specific data (Farber Disease Natural History Instrument - FDNI)&#xD;
Laboratory tests (laboratory assessments and inflammatory markers)&#xD;
Functional tests&#xD;
Six-minute walk test (6MWT)&#xD;
Pulmonary function testing&#xD;
Additional assessments and evaluations:&#xD;
Patient reported outcomes&#xD;
Pain assessment&#xD;
Relative impact of symptoms&#xD;
Nodule Impact Questionnaire&#xD;
Physician and Patient/Parent global assessment&#xD;
Measurement and clinical characteristics of index nodules&#xD;
Ultrasound evaluation of liver and spleen&#xD;
High-frequency ultrasound</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">45</enrollment>
  <condition>Farber Disease</condition>
  <condition>Farber's Disease</condition>
  <condition>Farber Lipogranulomatosis</condition>
  <condition>Acid Ceramidase Deficiency</condition>
  <condition>Ceramidase Deficiency</condition>
  <condition>N-Laurylsphingosine Deacylase Deficiency</condition>
  <condition>ASAH1 Mutation</condition>
  <arm_group>
    <arm_group_label>Living non-HSCT Farber Disease Patients</arm_group_label>
    <description>Patients with a confirmed diagnosis of Farber disease who are currently alive and have not undergone hematopoietic stem cell transplantation (HSCT).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Living HSCT Farber Disease Patients</arm_group_label>
    <description>Patients with a confirmed diagnosis of Farber disease who are currently alive and have undergone hematopoietic stem cell transplantation (HSCT).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Deceased Farber Disease Patients</arm_group_label>
    <description>Patients with a confirmed diagnosis of Farber disease who are deceased (including patients who may or may not have undergone hematopoietic stem cell transplantation).</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Whole blood will be retained.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        All identified patients with Farber disease, living or deceased, diagnosed by biochemical&#xD;
        or genetic criteria, or both, are eligible for inclusion in the study without regard to any&#xD;
        other baseline or demographic characteristics. Both subjects who have undergone HSCT and&#xD;
        those who have not are eligible to participate.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Living or deceased subjects with diagnosis of Farber disease, based on clinical&#xD;
             (typical clinical symptoms) and biochemical and/or genetic criteria, as follows:&#xD;
&#xD;
               -  Biochemical: An acid ceramidase activity value in white blood cells, cultured&#xD;
                  skin fibroblasts or other biological sources (e.g., plasma) that is less than 30%&#xD;
                  of control (normal) values established by the testing laboratory. For deceased&#xD;
                  subjects only, storage of ceramide in cells from histopathologic sections is also&#xD;
                  adequate to confirm the diagnosis.&#xD;
&#xD;
               -  Genetic: Nucleotide changes within both alleles of the acid ceramidase gene&#xD;
                  (ASAH1) or cDNA that indicate, through bioinformatics, gene expression studies,&#xD;
                  or other methods, a possible loss of function of the acid ceramidase protein.&#xD;
&#xD;
          -  Informed consent or assent, for living subjects. For deceased subjects it is the&#xD;
             responsibility of the principal investigator to ensure that the proper requirements&#xD;
             are met according to local laws and regulations.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        • Current use or history of use in the past 30 days of an investigational agent (with&#xD;
        exception of off-label use of medications).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UCSF Benioff Children's Hospital Oakland</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's National Health System</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Niños de la Santisima Trinidad</name>
      <address>
        <city>Córdoba</city>
        <state>CP</state>
        <zip>5000</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montreal Children's Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cairo University</name>
      <address>
        <city>Cairo</city>
        <country>Egypt</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Giessen, Zentrum für Kinderheilkunde und Jugendmedizin</name>
      <address>
        <city>Giessen</city>
        <state>Hessen</state>
        <zip>35392</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lok Nayak Hospital &amp; Maulana Azad Medical College</name>
      <address>
        <city>Dehli</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sir Ganga Ram Hospital</name>
      <address>
        <city>Delhi</city>
        <country>India</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Istituto Giannina Gaslini</name>
      <address>
        <city>Genoa</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Milan</name>
      <address>
        <city>Milan</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Astrid Lindgrens barnsjukhus, Karolinska University Hospital Solna</name>
      <address>
        <city>Stockholm</city>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cukurova University School of Medicine</name>
      <address>
        <city>Adana</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hacettepe University Medical Faculty Hospital</name>
      <address>
        <city>Ankara</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istanbul University Istanbul School of Medicine</name>
      <address>
        <city>Istanbul</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dokuz Eylul University School of Medicine</name>
      <address>
        <city>İzmir</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Canada</country>
    <country>Egypt</country>
    <country>Germany</country>
    <country>India</country>
    <country>Italy</country>
    <country>Sweden</country>
    <country>Turkey</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.enzyvant.com/</url>
    <description>Related Info</description>
  </link>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2017</study_first_posted>
  <last_update_submitted>January 14, 2020</last_update_submitted>
  <last_update_submitted_qc>January 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Natural History Study</keyword>
  <keyword>Observational Study</keyword>
  <keyword>Prospective Study</keyword>
  <keyword>Retrospective Study</keyword>
  <keyword>Farber Disease</keyword>
  <keyword>Farber's Disease</keyword>
  <keyword>ASAH1</keyword>
  <keyword>Subcutaneous Nodules</keyword>
  <keyword>Lysosomal Storage Disease</keyword>
  <keyword>Lysosomal Storage Disease, Nervous System</keyword>
  <keyword>Metabolic Diseases</keyword>
  <keyword>Lipid Metabolism Disorders</keyword>
  <keyword>Lipidoses</keyword>
  <keyword>Sphingolipidoses</keyword>
  <keyword>Genetic Disease, Inborn</keyword>
  <keyword>Musculoskeletal Diseases</keyword>
  <keyword>Connective Tissue Diseases</keyword>
  <keyword>Central Nervous System Diseases</keyword>
  <keyword>Brain Diseases, Metabolic, Inborn</keyword>
  <keyword>Brain Diseases, Metabolic</keyword>
  <keyword>Brain Diseases, Inborn</keyword>
  <keyword>Brain Diseases</keyword>
  <keyword>Infant, Newborn Diseases</keyword>
  <keyword>Inborn Errors of Metabolism</keyword>
  <keyword>Inherited Metabolic Disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Farber Lipogranulomatosis</mesh_term>
    <mesh_term>Erdheim-Chester Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03233841
org study id: RVT-801-0001
nct id: NCT03233841
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary objective of this study is to establish the natural history of Farber disease
      (acid ceramidase deficiency) through the collection and analysis of retrospective and
      prospective data on patients diagnosed with Farber disease. All patients diagnosed with
      Farber disease are eligible, including both those who have and have not undergone
      hematopoietic stem cell transplantation (HSCT). Additionally, data and records from deceased
      patients will provide valuable retrospective data for this study.

      The secondary objective of the study is to establish a set of clinical data, laboratory data
      (biomarkers), and functional data potentially useful for:

        -  Assessing the efficacy of HSCT and the efficacy of potential future therapies (for
           example with RVT-801, recombinant human acid ceramidase) in Farber disease

        -  Characterizing changes in symptoms of patients over time

        -  Characterizing distinct groups (phenotypes) within the patient population

        -  Documenting the disease histories of individual patients to serve as intra-subject
           control data for those who may enroll in any future clinical studies with therapies for
           Farber disease

      The exploratory objectives of the study are:

        -  To explore the relationship between patient disease activity or phenotype and specific
           ceramide levels or specific immunologic markers (cytokines/chemokines) in blood

        -  To evaluate a standardized tool, the Farber Disease Natural History Instrument (FDNI),
           to be used for the collection of patient history information, data from clinical,
           laboratory, genetic, and functional studies, and data from review of medical records
observational model: Cohort
time perspective: Other
measure: Establish a dataset on the natural history of Farber Disease
time frame: Up to 21 months
description: Collection of information for all subjects will include data from:
Medical history
Farber disease diagnosis, presentation, treatments and symptom progression
Collection of information from living subjects will include:
Medical examination
Disease-specific data (Farber Disease Natural History Instrument - FDNI)
Laboratory tests (laboratory assessments and inflammatory markers)
Functional tests
Six-minute walk test (6MWT)
Pulmonary function testing
Additional assessments and evaluations:
Patient reported outcomes
Pain assessment
Relative impact of symptoms
Nodule Impact Questionnaire
Physician and Patient/Parent global assessment
Measurement and clinical characteristics of index nodules
Ultrasound evaluation of liver and spleen
High-frequency ultrasound
arm group label: Living non-HSCT Farber Disease Patients
description: Patients with a confirmed diagnosis of Farber disease who are currently alive and have not undergone hematopoietic stem cell transplantation (HSCT).
arm group label: Living HSCT Farber Disease Patients
description: Patients with a confirmed diagnosis of Farber disease who are currently alive and have undergone hematopoietic stem cell transplantation (HSCT).
arm group label: Deceased Farber Disease Patients
description: Patients with a confirmed diagnosis of Farber disease who are deceased (including patients who may or may not have undergone hematopoietic stem cell transplantation).
Whole blood will be retained.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
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country: Argentina
country: Canada
country: Egypt
country: Germany
country: India
country: Italy
country: Sweden
country: Turkey
country: United States
url: http://www.enzyvant.com/
description: Related Info
responsible party type: Sponsor
mesh term: Farber Lipogranulomatosis
mesh term: Erdheim-Chester Disease
sharing ipd: No