A Prospective and Retrospective Cohort Study in Patients With Chronic Forms of Acid Sphingomyelinase Deficiency (ASMD)
Primary Purpose
Sphingomyelin Lipidosis
Status
Completed
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Investigational Procedures
Sponsored by
About this trial
This is an interventional other trial for Sphingomyelin Lipidosis
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.
Sites / Locations
- Investigational Site Number :8400002
- Investigational Site Number :8400003
- Investigational Site Number :8400001
- Investigational Site Number :0320002
- Investigational Site Number :0320001
- Investigational Site Number :0560001
- Investigational Site Number :0760001
- Investigational Site Number :0760002
- Investigational Site Number :0760006
- Investigational Site Number :152001
- Investigational Site Number :152002
- Investigational Site Number :2030001
- Investigational Site Number :2500002
- Investigational Site Number :2500003
- Investigational Site Number :2500001
- Investigational Site Number :2760002
- Investigational Site Number :2760005
- Investigational Site Number :380002
- Investigational Site Number :380001
- Investigational Site Number :6200001
- Investigational Site Number :6200002
- Investigational Site Number :6420001
- Investigational Site Number :7240005
- Investigational Site Number :7240001
- Investigational Site Number :7240004
- Investigational Site Number :7920005
- Investigational Site Number :7920003
- Investigational Site Number :7920001
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Acid Sphingomyelinase Deficiency (ASMD) Cohort
Arm Description
Patients across the full spectrum of chronic ASMD who have fulfilled the eligibility criteria and who have performed the inclusion visit
Outcomes
Primary Outcome Measures
Time of first occurrence and recurrence of the clinical features and medical interventions related to chronic ASMD
Number of patients with at least one clinical feature and highest severity grade at the time of diagnosis and over time
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)
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)
Secondary Outcome Measures
Number of patients with at least one abnormal value in laboratory parameters
Forced vital capacity (FVC) level over time since the time of diagnosis
Forced expiratory volume in the first second of the maneuver (FEV1)
Total lung capacity (TLC)
Diffusion capacity of CO (DLCO) Test
Pulse Oximetry: Saturation of Peripheral Oxygen (SpO2)
Liver volume
Liver stiffness score
Spleen volume
Bone maturation for age (pediatric patients only)
Age appropriate Z-score deviation for height and weight (children only)
Body mass index (BMI) for adults only
Optimization and validation of ASMD disease severity scoring system (DS3)
Validation of ASMD PRO instruments (24h and 7-day recall)
Niemann-Pick B Health Assessment Questionnaire
Health-related Productivity Questionnaire
Association of hepatomegaly with age, gender, race, Ashkenazi ancestry and genotype
Association of splenomegaly with age, gender, race, Ashkenazi ancestry and genotype
Association of lower respiratory tract infection with age, gender, race, Ashkenazi ancestry and genotype
Association of respiratory distress with age, gender, race, Ashkenazi ancestry and genotype
Association of oxygen therapy with age, gender, race, Ashkenazi ancestry and genotype
Association of external bleeding episode with age, gender, race, Ashkenazi ancestry and genotype
Association of myocardial infarction with age, gender, race, Ashkenazi ancestry and genotype
Association of cerebrovascular accident with age, gender, race, Ashkenazi ancestry and genotype
Association of hospitalization with age, gender, race, Ashkenazi ancestry and genotype
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04106544
Brief Title
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
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
September 27, 2019 (Actual)
Primary Completion Date
May 15, 2023 (Actual)
Study Completion Date
May 15, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sphingomyelin Lipidosis
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
84 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Acid Sphingomyelinase Deficiency (ASMD) Cohort
Arm Type
Other
Arm Description
Patients across the full spectrum of chronic ASMD who have fulfilled the eligibility criteria and who have performed the inclusion visit
Intervention Type
Procedure
Intervention Name(s)
Investigational Procedures
Intervention Description
The investigational assessments will be performed
Primary Outcome Measure Information:
Title
Time of first occurrence and recurrence of the clinical features and medical interventions related to chronic ASMD
Time Frame
Minimum 2 years
Title
Number of patients with at least one clinical feature and highest severity grade at the time of diagnosis and over time
Time Frame
Minimum 2 years
Title
Clinician-Reported Outcomes (ClinROs) depending on participant's age, local regulation, local availability and investigator's discretion
Description
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)
Time Frame
Up to 2 years
Title
Patient-Reported Outcomes (PROs) depending on participant's age, local regulation, local availability and investigator's discretion
Description
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)
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Number of patients with at least one abnormal value in laboratory parameters
Time Frame
Minimum 2 years
Title
Forced vital capacity (FVC) level over time since the time of diagnosis
Time Frame
Minimum 2 years
Title
Forced expiratory volume in the first second of the maneuver (FEV1)
Time Frame
Minimum 2 years
Title
Total lung capacity (TLC)
Time Frame
Minimum 2 years
Title
Diffusion capacity of CO (DLCO) Test
Time Frame
Minimum 2 years
Title
Pulse Oximetry: Saturation of Peripheral Oxygen (SpO2)
Time Frame
Minimum 2 years
Title
Liver volume
Time Frame
Minimum 2 years
Title
Liver stiffness score
Time Frame
Minimum 2 years
Title
Spleen volume
Time Frame
Minimum 2 years
Title
Bone maturation for age (pediatric patients only)
Time Frame
Minimum 2 years
Title
Age appropriate Z-score deviation for height and weight (children only)
Time Frame
Minimum 2 years
Title
Body mass index (BMI) for adults only
Time Frame
Minimum 2 years
Title
Optimization and validation of ASMD disease severity scoring system (DS3)
Time Frame
Up to 2 years
Title
Validation of ASMD PRO instruments (24h and 7-day recall)
Time Frame
UP to 2 years
Title
Niemann-Pick B Health Assessment Questionnaire
Time Frame
UP to 2 years
Title
Health-related Productivity Questionnaire
Time Frame
UP to 2 years
Title
Association of hepatomegaly with age, gender, race, Ashkenazi ancestry and genotype
Time Frame
Minimum 2 years
Title
Association of splenomegaly with age, gender, race, Ashkenazi ancestry and genotype
Time Frame
Minimum 2 years
Title
Association of lower respiratory tract infection with age, gender, race, Ashkenazi ancestry and genotype
Time Frame
Minimum 2 years
Title
Association of respiratory distress with age, gender, race, Ashkenazi ancestry and genotype
Time Frame
Minimum 2 years
Title
Association of oxygen therapy with age, gender, race, Ashkenazi ancestry and genotype
Time Frame
Minimum 2 years
Title
Association of external bleeding episode with age, gender, race, Ashkenazi ancestry and genotype
Time Frame
Minimum 2 years
Title
Association of myocardial infarction with age, gender, race, Ashkenazi ancestry and genotype
Time Frame
Minimum 2 years
Title
Association of cerebrovascular accident with age, gender, race, Ashkenazi ancestry and genotype
Time Frame
Minimum 2 years
Title
Association of hospitalization with age, gender, race, Ashkenazi ancestry and genotype
Time Frame
Minimum 2 years
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number :8400002
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Investigational Site Number :8400003
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Investigational Site Number :8400001
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Investigational Site Number :0320002
City
Caba
ZIP/Postal Code
1425
Country
Argentina
Facility Name
Investigational Site Number :0320001
City
Córdoba
ZIP/Postal Code
X5004FHP
Country
Argentina
Facility Name
Investigational Site Number :0560001
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Investigational Site Number :0760001
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90035-003
Country
Brazil
Facility Name
Investigational Site Number :0760002
City
São Paulo
ZIP/Postal Code
04020-041
Country
Brazil
Facility Name
Investigational Site Number :0760006
City
São Paulo
ZIP/Postal Code
05403000
Country
Brazil
Facility Name
Investigational Site Number :152001
City
Santiago
ZIP/Postal Code
753-0234
Country
Chile
Facility Name
Investigational Site Number :152002
City
Santiago
ZIP/Postal Code
8330077
Country
Chile
Facility Name
Investigational Site Number :2030001
City
Praha 2
ZIP/Postal Code
12808
Country
Czechia
Facility Name
Investigational Site Number :2500002
City
ANGERS Cedex 01
ZIP/Postal Code
49033
Country
France
Facility Name
Investigational Site Number :2500003
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Investigational Site Number :2500001
City
Paris
Country
France
Facility Name
Investigational Site Number :2760002
City
Gießen
ZIP/Postal Code
35392
Country
Germany
Facility Name
Investigational Site Number :2760005
City
Mainz
ZIP/Postal Code
65239
Country
Germany
Facility Name
Investigational Site Number :380002
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Facility Name
Investigational Site Number :380001
City
Udine
ZIP/Postal Code
33100
Country
Italy
Facility Name
Investigational Site Number :6200001
City
Porto
ZIP/Postal Code
4050-371
Country
Portugal
Facility Name
Investigational Site Number :6200002
City
Porto
ZIP/Postal Code
4200-319
Country
Portugal
Facility Name
Investigational Site Number :6420001
City
Timisoara
ZIP/Postal Code
300011
Country
Romania
Facility Name
Investigational Site Number :7240005
City
Barcelona
Country
Spain
Facility Name
Investigational Site Number :7240001
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Investigational Site Number :7240004
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Investigational Site Number :7920005
City
Adana
ZIP/Postal Code
01330
Country
Turkey
Facility Name
Investigational Site Number :7920003
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
Investigational Site Number :7920001
City
Izmir
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
Learn more about this trial
A Prospective and Retrospective Cohort Study in Patients With Chronic Forms of Acid Sphingomyelinase Deficiency (ASMD)
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