Data Analysis of Adult and Pediatric Participants With Acid Sphingomyelinase Deficiency (ASMD) on Early Access to Olipudase Alfa in France

Study Overview
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Brief Summary
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Primary Objective: To describe the lung, spleen and liver outcomes of olipudase alfa Secondary Objectives: To describe the patient's characteristics To describe conditions of olipudase alfa use To describe safety data related to the use of olipudase alfa To describe complementary effectiveness outcomes parameters

Detailed Description
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Approximate duration of enrollment: 18 months Total study duration: approximately 3 years This is a national, multicenter observational retrospective and prospective cohort data collection study. Retrospective is defined as collection of data from all patients, including deceased patients, who were already on early access olipudase alfa in France before the start of this study.

Official Title
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Acid Sphingomyelinase Deficiency (ASMD): Data Analysis of Adult and Pediatric Patients on Early Access to Olipudase Alfa in France

Conditions
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Acid Sphingomyelinase Deficiency (ASMD)

Intervention / Treatment
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* Drug: Olipudase alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient, or the patient's parent(s)/guardian(s), has signed written informed consent. Patients with a confirmed diagnosis of ASMD under early access to olipudase alfa in France (ie, nominative compassionate use, pre marketing authorization early access, post marketing authorization early access). The patient has documented deficiency of acid sphingomyelinase in peripheral leukocytes, lymphocytes, or cultured fibroblasts. Male and female patients of all ages. Exclusion Criteria: The patient or legal guardian(s) who has not received information notice or who opposes to data collection. Patient who died before study initiation and who was opposed to data collection for research purpose when he/she was alive. The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1<br>Patients with a confirmed diagnosis of ASMD under early access to olipudase alfa in France | Drug: Olipudase alfa<br>* GZ402665<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in pulmonary function diffusion capacity of lung for carbon monoxide (DLco) |  | From baseline to 6 months | 
| Change in spleen size |  | From baseline to 6 months | 
| Change in liver size |  | From baseline to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline patient characteristics | Demographic and baseline data [age, gender, phenotype of ASMD, acid sphingomyelinase activity in peripheral leukocytes, lymphocytes, or cultured fibroblasts, age at diagnosis, age at first symptom onset, history of splenectomy (month/year), habits (i.e., smoking, alcoholism), known metabolic conditions or diseases (obesity, diabetes, familial dyslipidemias), known respiratory diseases; known hepatic diseases; others)] | At baseline | 
| Condition of olipudase alfa use | Conditions of olipudase alfa use (time to reach maximum dose [3 mg/kg] or the maximum tolerated dose for the patient, center profile, treater specialty, need of a premedication before the infusion [if yes, precise], treatment duration [start and end dates], treatment discontinuation [Yes/No] and reason of treatment discontinuation if any) | From baseline up to 3 years | 
| Safety: AE | Number of Participants with Adverse events (AE) including infusion-associated reactions | From baseline up to 3 years | 
| Safety: immunogenicity | Immune response assessments (antibodies anti-olipudase alfa IgG) | From baseline up to 3 years | 
| Complementary effectiveness: change in pulmonary function DLco |  | From baseline to 12 months and every year up to 3 years | 
| Complementary effectiveness: change in spleen size |  | From baseline to 12 months and every year up to 3 years | 
| Complementary effectiveness: change in liver size |  | From baseline to 12 months and every year up to 3 years | 
| Change in interstitial pulmonary infiltration based on lung imaging (thoracic CT-scan) |  | From baseline to 12 months and every year if abnormal up to 3 years | 
| Change in platelet count |  | From baseline at 3, 6, 9, 12 months and every year up to 3 years | 
| Change in biomarkers (chitotriosidase and lysosphingomyelin) plasma levels |  | From baseline at 3, 6, 9, 12 months and every year up to 3 years | 
| Change in liver function | Alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total and direct bilirubin | From baseline at 3, 6, 9, 12 months and every year up to 3 years | 
| Change in lipid profile | total cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol | From baseline at 3, 6, 9, 12 months and every year up to 3 years | 
| Change in growth curve for pediatric patient |  | From baseline at 6, 12 months and every year up to 3 years |