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

NCT04106544 | Completed

• 1 other identifier: PIR16183
• Study Type: interventional
• Target: 84
• Locations: 13 countries
• Sites: 28

Brief Summary

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

Conditions

Sphingomyelin Lipidosis

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (25)

• 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

Study Arms (1)

Acid Sphingomyelinase Deficiency (ASMD) Cohort

OTHER

Patients across the full spectrum of chronic ASMD who have fulfilled the eligibility criteria and who have performed the inclusion visit

Procedure: Investigational Procedures

Interventions

Investigational Procedures PROCEDURE

The investigational assessments will be performed

Acid Sphingomyelinase Deficiency (ASMD) Cohort

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (28)

Investigational Site Number :8400002

Atlanta, Georgia, 30322, United States

Location

Investigational Site Number :8400003

The Bronx, New York, 10467, United States

Location

Investigational Site Number :8400001

Valhalla, New York, 10595, United States

Location

Investigational Site Number :0320002

CABA, 1425, Argentina

Location

Investigational Site Number :0320001

Córdoba, X5004FHP, Argentina

Location

Investigational Site Number :0560001

Leuven, 3000, Belgium

Location

Investigational Site Number :0760001

Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

Location

Investigational Site Number :0760002

São Paulo, 04020-041, Brazil

Location

Investigational Site Number :0760006

São Paulo, 05403000, Brazil

Location

Investigational Site Number :152001

Santiago, 753-0234, Chile

Location

Investigational Site Number :152002

Santiago, 8330077, Chile

Location

Investigational Site Number :2030001

Prague, 12808, Czechia

Location

Investigational Site Number :2500002

Angers, 49033, France

Location

Investigational Site Number :2500003

Paris, 75015, France

Location

Investigational Site Number :2500001

Paris, France

Location

Investigational Site Number :2760002

Giessen, 35392, Germany

Location

Investigational Site Number :2760005

Mainz, 65239, Germany

Location

Investigational Site Number :380002

Napoli, 80131, Italy

Location

Investigational Site Number :380001

Udine, 33100, Italy

Location

Investigational Site Number :6200001

Porto, 4050-371, Portugal

Location

Investigational Site Number :6200002

Porto, 4200-319, Portugal

Location

Investigational Site Number :6420001

Timișoara, 300011, Romania

Location

Investigational Site Number :7240005

Barcelona, Spain

Location

Investigational Site Number :7240001

Madrid, 28046, Spain

Location

Investigational Site Number :7240004

Seville, 41013, Spain

Location

Investigational Site Number :7920005

Adana, 01330, Turkey (Türkiye)

Location

Investigational Site Number :7920003

Istanbul, 34093, Turkey (Türkiye)

Location

Investigational Site Number :7920001

Izmir, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Niemann-Pick Disease, Type A

Condition Hierarchy (Ancestors)

Niemann-Pick Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2019
• First Posted: September 27, 2019
• Study Start: September 27, 2019
• Primary Completion: May 15, 2023
• Study Completion: May 15, 2023
• Last Updated: August 16, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

RO (1); AR (2); BE (1); TU (3); FR (3); BR (3); IT (2); ES (3); CZ (1); DE (2); CL (2); PT (2); US (3)