Clinical trial NCT04106544: A Prospective and Retrospective Cohort Study in Patients With Chronic Forms of Acid Sphingomyelinase Deficiency (ASMD)
Official title: A Prospective and Retrospective Cohort Study to Refine and Expand the Knowledge on Patients With Chronic Forms of Acid Sphingomyelinase Deficiency (ASMD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sphingomyelin Lipidosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2019-09-27
Enrollment: 84
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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

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.

Primary outcomes:
measure: Time of first occurrence and recurrence of the clinical features and medical interventions related to chronic ASMD
timeFrame: Minimum 2 years
measure: Number of patients with at least one clinical feature and highest severity grade at the time of diagnosis and over time
timeFrame: Minimum 2 years
measure: Clinician-Reported Outcomes (ClinROs) depending on participant's age, local regulation, local availability and investigator's discretion
timeFrame: Up to 2 years
measure: Patient-Reported Outcomes (PROs) depending on participant's age, local regulation, local availability and investigator's discretion
timeFrame: Up to 2 years
Secondary outcomes:
measure: Number of patients with at least one abnormal value in laboratory parameters
timeFrame: Minimum 2 years
measure: Forced vital capacity (FVC) level over time since the time of diagnosis
timeFrame: Minimum 2 years
measure: Forced expiratory volume in the first second of the maneuver (FEV1)
timeFrame: Minimum 2 years
measure: Total lung capacity (TLC)
timeFrame: Minimum 2 years
measure: Diffusion capacity of CO (DLCO) Test
timeFrame: Minimum 2 years
measure: Pulse Oximetry: Saturation of Peripheral Oxygen (SpO2)
timeFrame: Minimum 2 years
measure: Liver volume
timeFrame: Minimum 2 years
measure: Liver stiffness score
timeFrame: Minimum 2 years
measure: Spleen volume
timeFrame: Minimum 2 years
measure: Bone maturation for age (pediatric patients only)
timeFrame: Minimum 2 years
measure: Age appropriate Z-score deviation for height and weight (children only)
timeFrame: Minimum 2 years
measure: Body mass index (BMI) for adults only
timeFrame: Minimum 2 years
measure: Optimization and validation of ASMD disease severity scoring system (DS3)
timeFrame: Up to 2 years
measure: Validation of ASMD PRO instruments (24h and 7-day recall)
timeFrame: UP to 2 years
measure: Niemann-Pick B Health Assessment Questionnaire
timeFrame: UP to 2 years
measure: Health-related Productivity Questionnaire
timeFrame: UP to 2 years
measure: Association of hepatomegaly with age, gender, race, Ashkenazi ancestry and genotype
timeFrame: Minimum 2 years
measure: Association of splenomegaly with age, gender, race, Ashkenazi ancestry and genotype
timeFrame: Minimum 2 years
measure: Association of lower respiratory tract infection with age, gender, race, Ashkenazi ancestry and genotype
timeFrame: Minimum 2 years
measure: Association of respiratory distress with age, gender, race, Ashkenazi ancestry and genotype
timeFrame: Minimum 2 years
measure: Association of oxygen therapy with age, gender, race, Ashkenazi ancestry and genotype
timeFrame: Minimum 2 years
measure: Association of external bleeding episode with age, gender, race, Ashkenazi ancestry and genotype
timeFrame: Minimum 2 years
measure: Association of myocardial infarction with age, gender, race, Ashkenazi ancestry and genotype
timeFrame: Minimum 2 years
measure: Association of cerebrovascular accident with age, gender, race, Ashkenazi ancestry and genotype
timeFrame: Minimum 2 years
measure: Association of hospitalization with age, gender, race, Ashkenazi ancestry and genotype
timeFrame: Minimum 2 years
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Investigational Site Number :8400002
state: Georgia
city: Bronx
country: United States
facility: Investigational Site Number :8400003
state: New York
city: Valhalla
country: United States
facility: Investigational Site Number :8400001
state: New York
city: Caba
country: Argentina
facility: Investigational Site Number :0320002
city: Córdoba
country: Argentina
facility: Investigational Site Number :0320001
city: Leuven
country: Belgium
facility: Investigational Site Number :0560001
city: Porto Alegre
country: Brazil
facility: Investigational Site Number :0760001
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: Investigational Site Number :0760002
city: São Paulo
country: Brazil
facility: Investigational Site Number :0760006
city: Santiago
country: Chile
facility: Investigational Site Number :152001
city: Santiago
country: Chile
facility: Investigational Site Number :152002
city: Praha 2
country: Czechia
facility: Investigational Site Number :2030001
city: ANGERS Cedex 01
country: France
facility: Investigational Site Number :2500002
city: Paris
country: France
facility: Investigational Site Number :2500003
city: Paris
country: France
facility: Investigational Site Number :2500001
city: Gießen
country: Germany
facility: Investigational Site Number :2760002
city: Mainz
country: Germany
facility: Investigational Site Number :2760005
city: Napoli
country: Italy
facility: Investigational Site Number :380002
city: Udine
country: Italy
facility: Investigational Site Number :380001
city: Porto
country: Portugal
facility: Investigational Site Number :6200001
city: Porto
country: Portugal
facility: Investigational Site Number :6200002
city: Timisoara
country: Romania
facility: Investigational Site Number :6420001
city: Barcelona
country: Spain
facility: Investigational Site Number :7240005
city: Madrid
country: Spain
facility: Investigational Site Number :7240001
city: Sevilla
country: Spain
facility: Investigational Site Number :7240004
city: Adana
country: Turkey
facility: Investigational Site Number :7920005
city: Istanbul
country: Turkey
facility: Investigational Site Number :7920003
city: Izmir
country: Turkey
facility: Investigational Site Number :7920001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: