Farber Disease Natural History Study

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

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

Study Overview

• Status: Completed
• Conditions: Farber Disease; Farber's Disease; Farber Lipogranulomatosis; Acid Ceramidase Deficiency; Ceramidase Deficiency; N-Laurylsphingosine Deacylase Deficiency; ASAH1 Mutation

• Study Type: Observational
• Enrollment (Actual): 45

Contacts and Locations

Study Locations

• Argentina
  • CP
    • Córdoba, CP, Argentina, 5000
      • Hospital de Niños de La Santisima Trinidad
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Montreal Children's Hospital
• Egypt
  • Cairo, Egypt
    • Cairo University
• Germany
  • Hessen
    • Giessen, Hessen, Germany, 35392
      • Universitätsklinikum Giessen, Zentrum für Kinderheilkunde und Jugendmedizin
• India
  • Dehli, India
    • Lok Nayak Hospital & Maulana Azad Medical College
  • Delhi, India
    • Sir Ganga Ram Hospital
• Italy
  • Genoa, Italy
    • IRCCS Istituto Giannina Gaslini
  • Milan, Italy
    • University of Milan
• Sweden
  • Stockholm, Sweden
    • Astrid Lindgrens barnsjukhus, Karolinska University Hospital Solna
• Turkey
  • Adana, Turkey
    • Cukurova University School of Medicine
  • Ankara, Turkey
    • Hacettepe University Medical Faculty Hospital
  • Istanbul, Turkey
    • Istanbul University Istanbul School of Medicine
  • İzmir, Turkey
    • Dokuz Eylul University School of Medicine
• United States
  • California
    • Oakland, California, United States, 94609
      • UCSF Benioff Children's Hospital Oakland
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All identified patients with Farber disease, living or deceased, diagnosed by biochemical or genetic criteria, or both, are eligible for inclusion in the study without regard to any other baseline or demographic characteristics. Both subjects who have undergone HSCT and those who have not are eligible to participate.

Description

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).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Living non-HSCT Farber Disease Patients; 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; Patients with a confirmed diagnosis of Farber disease who are currently alive and have undergone hematopoietic stem cell transplantation (HSCT).
Deceased Farber Disease Patients; 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?

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 testsSix-minute walk test (6MWT)Pulmonary function testing; Additional assessments and evaluations:Patient reported outcomesPain assessmentRelative impact of symptomsNodule Impact QuestionnairePhysician and Patient/Parent global assessmentMeasurement and clinical characteristics of index nodulesUltrasound evaluation of liver and spleenHigh-frequency ultrasound	Up to 21 months

Collaborators and Investigators

• Sponsor: Enzyvant Therapeutics GmBH

Publications and helpful links

General Publications

• Elsea SH, Solyom A, Martin K, Harmatz P, Mitchell J, Lampe C, Grant C, Selim L, Mungan NO, Guelbert N, Magnusson B, Sundberg E, Puri R, Kapoor S, Arslan N, DiRocco M, Zaki M, Ozen S, Mahmoud IG, Ehlert K, Hahn A, Gokcay G, Torcoletti M, Ferreira CR. ASAH1 pathogenic variants associated with acid ceramidase deficiency: Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy. Hum Mutat. 2020 Sep;41(9):1469-1487. doi: 10.1002/humu.24056. Epub 2020 Jun 24.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2017
• Primary Completion (Actual): October 12, 2019
• Study Completion (Actual): December 9, 2019

Study Registration Dates

• First Submitted: July 26, 2017
• First Submitted That Met QC Criteria: July 26, 2017
• First Posted (Actual): July 31, 2017

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 14, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Connective Tissue Diseases; Observational Study; Central Nervous System Diseases; Musculoskeletal Diseases; Natural History Study; Lipid Metabolism Disorders; Brain Diseases; Metabolic Diseases; Inborn Errors of Metabolism; Lipidoses; Retrospective Study; Lysosomal Storage Disease; Prospective Study; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Brain Diseases, Metabolic; Farber Disease; Farber's Disease; ASAH1; Subcutaneous Nodules; Lysosomal Storage Disease, Nervous System; Genetic Disease, Inborn; Brain Diseases, Inborn; Infant, Newborn Diseases; Inherited Metabolic Disease
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lymphatic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Erdheim-Chester Disease; Farber Lipogranulomatosis
• Other Study ID Numbers: RVT-801-0001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No