Farber Disease Natural History Study

Study Overview
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Brief Summary
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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

Official Title
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Observational and Cross-Sectional Cohort Study of the Natural History and Phenotypic Spectrum of Farber Disease

Conditions
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ASAH1 Mutation, Farber Disease, Farber's Disease, Farber Lipogranulomatosis, Acid Ceramidase Deficiency, Ceramidase Deficiency, N-Laurylsphingosine Deacylase Deficiency

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Living or deceased subjects with diagnosis of Farber disease, based on clinical (typical clinical symptoms) and biochemical and/or genetic criteria, as follows: Biochemical: An acid ceramidase activity value in white blood cells, cultured skin fibroblasts or other biological sources (e.g., plasma) that is less than 30% of control (normal) values established by the testing laboratory. For deceased subjects only, storage of ceramide in cells from histopathologic sections is also adequate to confirm the diagnosis. Genetic: Nucleotide changes within both alleles of the acid ceramidase gene (ASAH1) or cDNA that indicate, through bioinformatics, gene expression studies, or other methods, a possible loss of function of the acid ceramidase protein. Informed consent or assent, for living subjects. For deceased subjects it is the responsibility of the principal investigator to ensure that the proper requirements are met according to local laws and regulations. Exclusion Criteria: • Current use or history of use in the past 30 days of an investigational agent (with exception of off-label use of medications).
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Living non-HSCT Farber Disease Patients<br>Patients with a confirmed diagnosis of Farber disease who are currently alive and have not undergone hematopoietic stem cell transplantation (HSCT). | |
| Living HSCT Farber Disease Patients<br>Patients with a confirmed diagnosis of Farber disease who are currently alive and have undergone hematopoietic stem cell transplantation (HSCT). | |
| Deceased Farber Disease Patients<br>Patients with a confirmed diagnosis of Farber disease who are deceased (including patients who may or may not have undergone hematopoietic stem cell transplantation). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish a dataset on the natural history of Farber Disease | 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 | Up to 21 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lysosomal Storage Disease, Natural History Study, Observational Study, Prospective Study, Retrospective Study, Farber Disease, Farber's Disease, ASAH1, Subcutaneous Nodules, Lysosomal Storage Disease, Nervous System, Metabolic Diseases, Lipid Metabolism Disorders, Lipidoses, Sphingolipidoses, Genetic Disease, Inborn, Musculoskeletal Diseases, Connective Tissue Diseases, Central Nervous System Diseases, Brain Diseases, Metabolic, Inborn, Brain Diseases, Metabolic, Brain Diseases, Inborn, Brain Diseases, Infant, Newborn Diseases, Inborn Errors of Metabolism, Inherited Metabolic Disease