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

Sphingomyelin Lipidosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04106544
• Other study ID #: PIR16183
• Status: Completed
• Phase: N/A
• Start date: September 27, 2019
• Est. completion date: May 15, 2023

Study information

• Verified date: August 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: May 15, 2023
• Est. primary completion date: May 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Niemann-Pick Disease, Type C
• Niemann-Pick Diseases
• Sphingomyelin Lipidosis

Intervention

Procedure:
• Investigational Procedures
The investigational assessments will be performed

Locations

Country	Name	City	State
Argentina	Investigational Site Number :0320002	Caba
Argentina	Investigational Site Number :0320001	Córdoba
Belgium	Investigational Site Number :0560001	Leuven
Brazil	Investigational Site Number :0760001	Porto Alegre	Rio Grande Do Sul
Brazil	Investigational Site Number :0760002	São Paulo
Brazil	Investigational Site Number :0760006	São Paulo
Chile	Investigational Site Number :152001	Santiago
Chile	Investigational Site Number :152002	Santiago
Czechia	Investigational Site Number :2030001	Praha 2
France	Investigational Site Number :2500002	ANGERS Cedex 01
France	Investigational Site Number :2500001	Paris
France	Investigational Site Number :2500003	Paris
Germany	Investigational Site Number :2760002	Gießen
Germany	Investigational Site Number :2760005	Mainz
Italy	Investigational Site Number :380002	Napoli
Italy	Investigational Site Number :380001	Udine
Portugal	Investigational Site Number :6200001	Porto
Portugal	Investigational Site Number :6200002	Porto
Romania	Investigational Site Number :6420001	Timisoara
Spain	Investigational Site Number :7240005	Barcelona
Spain	Investigational Site Number :7240001	Madrid
Spain	Investigational Site Number :7240004	Sevilla
Turkey	Investigational Site Number :7920005	Adana
Turkey	Investigational Site Number :7920003	Istanbul
Turkey	Investigational Site Number :7920001	Izmir
United States	Investigational Site Number :8400002	Atlanta	Georgia
United States	Investigational Site Number :8400003	Bronx	New York
United States	Investigational Site Number :8400001	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Chile,  Czechia,  France,  Germany,  Italy,  Portugal,  Romania,  Spain,  Turkey, 

Outcome

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