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

Study Overview
=================
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

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

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

Conditions
-----------------
Sphingomyelin Lipidosis

Intervention / Treatment
-----------------
* Procedure: Investigational Procedures


Participation Criteria
=================
Eligibility Criteria
-----------------
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.
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

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 | Measure Description | 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 |