Farber Disease Natural History Study

NCT03233841 | Completed

• 1 other identifier: RVT-801-0001
• Study Type: observational
• Target: 45
• Locations: 9 countries
• Sites: 15

Brief Summary

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

Conditions

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

Keywords

Natural History Study; Observational Study; Prospective Study; Retrospective Study; Farber Disease; Farber's Disease; ASAH1; Subcutaneous Nodules; Lysosomal Storage Disease; 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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

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).

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• Current use or history of use in the past 30 days of an investigational agent (with exception of off-label use of medications).

Sponsors & Collaborators

• Sumitomo Pharma Switzerland GmbH: lead

Study Sites (15)

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Children's National Health System

Washington D.C., District of Columbia, 20010, United States

Location

Hospital de Niños de la Santisima Trinidad

Córdoba, CP, 5000, Argentina

Location

Montreal Children's Hospital

Montreal, Quebec, H4A 3J1, Canada

Location

Cairo University

Cairo, Egypt

Location

Universitätsklinikum Giessen, Zentrum für Kinderheilkunde und Jugendmedizin

Giessen, Hesse, 35392, Germany

Location

Lok Nayak Hospital & Maulana Azad Medical College

Dehli, India

Location

Sir Ganga Ram Hospital

Delhi, India

Location

IRCCS Istituto Giannina Gaslini

Genoa, Italy

Location

University of Milan

Milan, Italy

Location

Astrid Lindgrens barnsjukhus, Karolinska University Hospital Solna

Stockholm, Sweden

Location

Cukurova University School of Medicine

Adana, Turkey (Türkiye)

Location

Hacettepe University Medical Faculty Hospital

Ankara, Turkey (Türkiye)

Location

Istanbul University Istanbul School of Medicine

Istanbul, Turkey (Türkiye)

Location

Dokuz Eylul University School of Medicine

Izmir, Turkey (Türkiye)

Location

Related Publications (1)

• 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.

  PMID: 32449975 DERIVED

Related Links

• Related Info

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood will be retained.

MeSH Terms

Conditions

Farber Lipogranulomatosis; Lysosomal Storage Diseases; Neurologic Manifestations; Metabolic Diseases; Lipid Metabolism Disorders; Lipidoses; Sphingolipidoses; Genetic Diseases, Inborn; Musculoskeletal Diseases; Connective Tissue Diseases; Central Nervous System Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Infant, Newborn, Diseases; Metabolism, Inborn Errors

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases, Nervous System; Nervous System Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipid Metabolism, Inborn Errors; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2017
• First Posted: July 31, 2017
• Study Start: November 22, 2017
• Primary Completion: October 12, 2019
• Study Completion: December 9, 2019
• Last Updated: January 18, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); IN (2); EG (1); IT (2); AR (1); US (2); CA (1); SE (1); TU (4)