A Prospective and Retrospective Cohort Study in Patients With Chronic Forms of Acid Sphingomyelinase Deficiency (ASMD)

A Prospective and Retrospective Cohort Study to Refine and Expand the Knowledge on Patients With Chronic Forms of Acid Sphingomyelinase Deficiency (ASMD)

Primary Objective:

• To describe the clinical features and their severity at the time of diagnosis and their evolution over time in patients with confirmed chronic visceral and chronic neurovisceral forms of ASMD
• To describe Clinician-Reported Outcomes (ClinROs) and Patient-Reported Outcomes (PROs) at enrollment and their evolution over time; disease severity at the time of diagnosis and its evolution over time

Secondary Objectives:

• To describe abnormal values in laboratory parameters and all values of specific clinical and imaging assessments at the time of diagnosis and their evolution over time
• To study the use and applicability towards validation of a newly developed ASMD disease severity scoring system
• To study the use and applicability towards validation of a newly developed ASMD PRO tool
• To describe ASMD-related disease burden among patients with ASMD, caregivers, and healthcare resource utilization
• To describe the association between patient demographics (eg, age, gender, race, Ashkenazi ancestry) and genotype with selected clinical features in patients with confirmed chronic visceral and chronic neurovisceral forms of ASMD

Study Overview

• Status: Completed
• Conditions: Sphingomyelin Lipidosis
• Intervention / Treatment: Procedure: Investigational Procedures

Detailed Description

Estimated average of study duration (for each patient) is 2 years

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, 1425
    • Investigational Site Number :0320002
  • Córdoba, Argentina, X5004FHP
    • Investigational Site Number :0320001
• Belgium
  • Leuven, Belgium, 3000
    • Investigational Site Number :0560001
• Brazil
  • São Paulo, Brazil, 04020-041
    • Investigational Site Number :0760002
  • São Paulo, Brazil, 05403000
    • Investigational Site Number :0760006
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-003
      • Investigational Site Number :0760001
• Chile
  • Santiago, Chile, 753-0234
    • Investigational Site Number :152001
  • Santiago, Chile, 8330077
    • Investigational Site Number :152002
• Czechia
  • Praha 2, Czechia, 12808
    • Investigational Site Number :2030001
• France
  • ANGERS Cedex 01, France, 49033
    • Investigational Site Number :2500002
  • Paris, France, 75015
    • Investigational Site Number :2500003
  • Paris, France
    • Investigational Site Number :2500001
• Germany
  • Gießen, Germany, 35392
    • Investigational Site Number :2760002
  • Mainz, Germany, 65239
    • Investigational Site Number :2760005
• Italy
  • Napoli, Italy, 80131
    • Investigational Site Number :380002
  • Udine, Italy, 33100
    • Investigational Site Number :380001
• Portugal
  • Porto, Portugal, 4200-319
    • Investigational Site Number :6200002
  • Porto, Portugal, 4050-371
    • Investigational Site Number :6200001
• Romania
  • Timisoara, Romania, 300011
    • Investigational Site Number :6420001
• Spain
  • Barcelona, Spain
    • Investigational Site Number :7240005
  • Madrid, Spain, 28046
    • Investigational Site Number :7240001
  • Sevilla, Spain, 41013
    • Investigational Site Number :7240004
• Turkey
  • Adana, Turkey, 01330
    • Investigational Site Number :7920005
  • Istanbul, Turkey, 34093
    • Investigational Site Number :7920003
  • Izmir, Turkey
    • Investigational Site Number :7920001
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Investigational Site Number :8400002
  • New York
    • Bronx, New York, United States, 10467
      • Investigational Site Number :8400003
    • Valhalla, New York, United States, 10595
      • Investigational Site Number :8400001

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria :

• Patients with confirmed diagnosis of chronic forms of ASMD based on 1) a clinical diagnosis consistent with chronic visceral ASMD (ie, NPD B) or chronic neurovisceral ASMD (ie, NPD B variant or intermediate NPD A/B) and 2) deficient enzymatic activity (as measured in peripheral leukocytes, cultured fibroblasts, lymphocytes, or DBS) or presence of 2 pathogenic SMPD1 mutations,
• The patient (or patient's legal guardian) must provide signed informed consent.

Exclusion criteria:

Patients suspected or diagnosed with infantile onset ASMD (ie, NPD A, with progressive developmental delay, or presence of any combination of R498L, L304P, and P333fs*52 genotypes, if available),

• Patients having received or receiving an investigational drug,
• Patients receiving any ASMD specific ERT,
• Patients with poor general condition that would not be able to undergo study assessments as per investigator's clinical judgment.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Acid Sphingomyelinase Deficiency (ASMD) Cohort; Patients across the full spectrum of chronic ASMD who have fulfilled the eligibility criteria and who have performed the inclusion visit	Procedure: Investigational Procedures; The investigational assessments will be performed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of first occurrence and recurrence of the clinical features and medical interventions related to chronic ASMD		Minimum 2 years
Number of patients with at least one clinical feature and highest severity grade at the time of diagnosis and over time		Minimum 2 years
Clinician-Reported Outcomes (ClinROs) depending on participant's age, local regulation, local availability and investigator's discretion	Clinical Global Impression rating scale (CGI, modified), Neuropathy Symptoms Score (NSS) , Neuropathy Disability Score(NDS), Brief Ataxia Rating Scale (BARS), The Essential Tremor Rating Assessment Scale (TETRAS), Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition (WPPSI™ - IV) , Wechsler Intelligence Scale for Children - Fifth Edition (WISC®-V) and Mini-Mental State Examination (MMSE)	Up to 2 years
Patient-Reported Outcomes (PROs) depending on participant's age, local regulation, local availability and investigator's discretion	EuroQol-5D-5L , EQ-5D-Y, Pediatric Quality of Life Inventory (PedsQL) core module, 36-Item Short Form Health Survey (SF-36) version 2 , MMRC dyspnea score, PedsQL Multidimensional Fatigue Scale, PedsQL Pediatric Pain Questionnaire, splenomegaly-related symptoms (SRS) v3, Patient Global Impression of Change (PGIC), Patient Global Impression of Symptom Severity (PGIS)	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients with at least one abnormal value in laboratory parameters	Minimum 2 years
Forced vital capacity (FVC) level over time since the time of diagnosis	Minimum 2 years
Forced expiratory volume in the first second of the maneuver (FEV1)	Minimum 2 years
Total lung capacity (TLC)	Minimum 2 years
Diffusion capacity of CO (DLCO) Test	Minimum 2 years
Pulse Oximetry: Saturation of Peripheral Oxygen (SpO2)	Minimum 2 years
Liver volume	Minimum 2 years
Liver stiffness score	Minimum 2 years
Spleen volume	Minimum 2 years
Bone maturation for age (pediatric patients only)	Minimum 2 years
Age appropriate Z-score deviation for height and weight (children only)	Minimum 2 years
Body mass index (BMI) for adults only	Minimum 2 years
Optimization and validation of ASMD disease severity scoring system (DS3)	Up to 2 years
Validation of ASMD PRO instruments (24h and 7-day recall)	UP to 2 years
Niemann-Pick B Health Assessment Questionnaire	UP to 2 years
Health-related Productivity Questionnaire	UP to 2 years
Association of hepatomegaly with age, gender, race, Ashkenazi ancestry and genotype	Minimum 2 years
Association of splenomegaly with age, gender, race, Ashkenazi ancestry and genotype	Minimum 2 years
Association of lower respiratory tract infection with age, gender, race, Ashkenazi ancestry and genotype	Minimum 2 years
Association of respiratory distress with age, gender, race, Ashkenazi ancestry and genotype	Minimum 2 years
Association of oxygen therapy with age, gender, race, Ashkenazi ancestry and genotype	Minimum 2 years
Association of external bleeding episode with age, gender, race, Ashkenazi ancestry and genotype	Minimum 2 years
Association of myocardial infarction with age, gender, race, Ashkenazi ancestry and genotype	Minimum 2 years
Association of cerebrovascular accident with age, gender, race, Ashkenazi ancestry and genotype	Minimum 2 years
Association of hospitalization with age, gender, race, Ashkenazi ancestry and genotype	Minimum 2 years

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2019
• Primary Completion (Actual): May 15, 2023
• Study Completion (Actual): May 15, 2023

Study Registration Dates

• First Submitted: September 4, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (Actual): September 27, 2019

Study Record Updates

• Last Update Posted (Actual): August 16, 2023
• Last Update Submitted That Met QC Criteria: August 15, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• 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; Lipid Metabolism, Inborn Errors; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Niemann-Pick Diseases; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type C; Lipidoses
• Other Study ID Numbers: PIR16183

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

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