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

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

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

Study Overview

• Status: Completed
• Conditions: Acid Sphingomyelinase Deficiency (ASMD)
• Intervention / Treatment: Drug: Olipudase alfa

Detailed Description

Approximate duration of enrollment: 30 months

Total study duration: approximately 30 months

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.

• Study Type: Observational
• Enrollment (Actual): 40

Contacts and Locations

Study Locations

• France
  • France, France
    • Investigational site in France

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients with a confirmed diagnosis of ASMD under early access to olipudase alfa in France (with a written informed consent)

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1; Patients with a confirmed diagnosis of ASMD under early access to olipudase alfa in France	Drug: Olipudase alfa; GZ402665

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in pulmonary function diffusion capacity of lung for carbon monoxide (DLco)	From baseline to 24 months
Change in spleen size	From baseline to 24 months
Change in liver size	From baseline to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Change in biomarkers (chitotriosidase and lysosphingomyelin) plasma levels		From baseline at 3, 6, 9, 12 months and every year up to 3 years
Baseline patient characteristics	Demographic and baseline data [age, gender, weight, phenotype and genotype 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
Complementary effectiveness: change in pulmonary function DLco		From baseline to 12 months and 36 months
Complementary effectiveness: change in spleen size		From baseline to 12 months and 36 months
Complementary effectiveness: change in liver size		FFrom baseline to 12 months and 36 months
Change in interstitial pulmonary infiltration based on lung imaging (thoracic CT-scan)		From baseline to 12 months and 24 months
Change in platelet count		From baseline at 3, 6, 9, 12, 24 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, 24 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, 24 months and every year up to 3 years
Change in growth curve for pediatric patient		From baseline at 6, 12, 24 months and every year up to 3 years
Change in weight		From baseline to 12 months and 36 months
Number of Participants with Evolution of Comorbidities	Number of participants with evolution of comorbidities will be assessed by grade, attenuation or disappearance/absence	From baseline to 12 months, 24 months and 36 months

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2022
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: April 28, 2022
• First Submitted That Met QC Criteria: April 28, 2022
• First Posted (Actual): May 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 5, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lymphatic Diseases; Lipid Metabolism Disorders; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Sphingolipidoses; Lipidoses; Niemann-Pick Diseases; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type C
• Other Study ID Numbers: OBS17422

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No