A Long-Term Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency

A Long-Term Study to Assess the Ongoing Safety and Efficacy of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency

The primary objective of this study is to obtain data regarding the safety of olipudase alfa in patients with acid sphingomyelinase deficiency (ASMD) who are exposed to long term treatment with olipudase alfa.

The secondary objectives of this study are to obtain data regarding the efficacy of olipudase alfa and to characterize olipudase alfa pharmacodynamics (PD) and pharmacokinetics (PK) following long-term administration.

Study Overview

• Status: Completed
• Conditions: Sphingomyelin Lipidosis
• Intervention / Treatment: Drug: GZ402665

Detailed Description

The maximum study duration per patient is 9 years or until olipudase alfa becomes commercially accessible (see maximum duration below), whichever comes first, unless the patient decides to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa is commercially accessible. The term "commercially accessible" is defined as when olipudase alfa is commercially accessible to each patient on an individual basis (eg, reimbursement being in place). The duration of study treatment with olipudase alfa between the local Regulatory approval and commercial accessibility should not exceed 90 days. Therefore, as described below, after local Regulatory approval, the patient can continue in the LTS13632 study for a maximum of 127 days. This will ensure 90 days of study treatment with olipudase alfa for patients after local Regulatory approval and a safety follow up phone call 30 to 37 days after the last dose of study treatment.

Notwithstanding the above, every pediatric patient will be treated in the LTS13632 study for at least 3 years to comply with the requirements agreed in the olipudase alfa Pediatric Investigational Plan.

The patient can switch immediately after the end of study treatment to commercial treatment without any gap in order to ensure continuity of treatment with olipudase alfa.

This study is an extension study for patients who have completed a previous study with olipudase alfa (DFI13803 for pediatric patients and DFI13412 for adult patients).

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Investigational Site Number 056001
• Brazil
  • Porto Alegre, Brazil, 90035 003
    • Investigational Site Number 076001
• France
  • Bron Cedex, France, 69677
    • Investigational Site Number 250002
• Germany
  • Hochheim Am Main, Germany, 65239
    • Investigational Site Number 276002
• Italy
  • Sassari, Italy, 07100
    • Investigational Site Number 380002
  • Udine, Italy, 33100
    • Investigational Site Number 380001
• United Kingdom
  • London, United Kingdom, WC1N 3JZ
    • Investigational Site Number 826001
  • Manchester, United Kingdom, M13 9WL
    • Investigational Site Number 826002
• United States
  • New York
    • New York, New York, United States, 10029-6574
      • Investigational Site Number 840001

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

• The patient completed the treatment period of a previous study of olipudase alfa with an acceptable safety profile in the opinion of the investigator and sponsor.
• The patient and/or the patient's parent(s)/legal guardian(s) is willing and able to provide signed written informed consent.
• The patient who is female and of childbearing potential must have a negative urine pregnancy test for beta human chorionic gonadotropin (β HCG).
• Female patients of childbearing potential and sexually mature male patients must be willing to practice true abstinence in line with their preferred and usual lifestyle or use 2 acceptable effective methods of contraception up to 15 days following their last dose of study drug.

Exclusion criteria:

• The patient has any new condition or worsening of an existing condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study.
• The patient, in the opinion of the investigator, is unable to adhere to the requirements of the study.
• The patient is unwilling or unable to abstain from the use of alcohol for 1 day prior to and 3 days after each olipudase alfa infusion for the duration of the treatment period.
• The patient is unwilling or unable to avoid, for 10 days before and 3 days after liver biopsies, medications or herbal supplements that are potentially hepatotoxic (eg, 3 hydroxy 3 methylglutaryl coenzyme A reductase inhibitors, erythromycin, valproic acid, antidepressants, kava, echinacea) or may cause or prolong bleeding (eg, anticoagulants, ibuprofen, aspirin, garlic supplements, ginkgo, ginseng) (only patients who previously participated in the DFI13412 study).
• The patient requires medication(s) that may decrease olipudase alfa activity (eg, fluoxetine, chlorpromazine; tricyclic antidepressants [eg, imipramine, desipramine]).

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: GZ402665; GZ402665 administered intravenously once every 2 weeks at the dose each patient was receiving at the end of their previous olipudase alfa study, for 9 years or until olipudase alfa becomes commercially accessible, whichever comes first, unless the patient decides to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa is commercially accessible.

Drug: GZ402665; Pharmaceutical form: Powder for concentrate for solution for infusion Route of administration: intravenous infusion; Other Names: Olipudase alfa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AEs)/treatment-emergent adverse events (TEAEs), including infusion-associated reactions and adverse events of special interest (AESIs)	Number of patients experiencing AEs, TEAEs, or AESIs	Baseline to up to 9 years
Complete physical examinations including extended neurologic and abbreviated physical exams		Baseline to up to 9 years
Vital signs, electrocardiograms and echocardiograms with Doppler		Baseline to up to 9 years
Clinical laboratory tests		Baseline to up to 9 years
Safety biomarkers		Baseline to up to 9 years
Liver biopsy (patients previously enrolled in DFI13412)		Baseline to after at least 3 years in the study
Liver ultrasound/Doppler (patients previously enrolled in DFI13803)		Baseline to 5 years
Immune response assessments		Baseline to up to 9 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spleen and liver volume	Abdominal magnetic resonance imaging (MRI) to evaluate improvements in spleen and liver volume	Baseline to up to 9 years
Pulmonary imaging		Baseline to up to 9 years
Pulmonary function test		Baseline to up to 9 years
Hematology	(hemoglobin and platelet count)	Baseline to up to 9 years
Lipid profile		Baseline to up to 9 years
Health outcome questionnaires (adults and pediatric)		Baseline to up to 9 years
Hand X ray for bone age and bone maturation (pediatric patients)		Baseline to up to 9 years
Linear patient growth by height Z -score (pediatric patients)		Baseline to up to 9 years

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Thurberg BL, Diaz GA, Lachmann RH, Schiano T, Wasserstein MP, Ji AJ, Zaher A, Peterschmitt MJ. Long-term efficacy of olipudase alfa in adults with acid sphingomyelinase deficiency (ASMD): Further clearance of hepatic sphingomyelin is associated with additional improvements in pro- and anti-atherogenic lipid profiles after 42 months of treatment. Mol Genet Metab. 2020 Sep-Oct;131(1-2):245-252. doi: 10.1016/j.ymgme.2020.06.010. Epub 2020 Jun 24.
• Wasserstein MP, Diaz GA, Lachmann RH, Jouvin MH, Nandy I, Ji AJ, Puga AC. Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months. J Inherit Metab Dis. 2018 Sep;41(5):829-838. doi: 10.1007/s10545-017-0123-6. Epub 2018 Jan 5.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2013
• Primary Completion (Actual): September 6, 2023
• Study Completion (Actual): September 6, 2023

Study Registration Dates

• First Submitted: November 26, 2013
• First Submitted That Met QC Criteria: December 4, 2013
• First Posted (Estimated): December 9, 2013

Study Record Updates

• Last Update Posted (Actual): September 25, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lymphatic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipid Metabolism, Inborn Errors; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Niemann-Pick Diseases; Niemann-Pick Disease, Type A; Niemann-Pick Disease, Type C; Lipidoses
• Other Study ID Numbers: LTS13632; 2013-000051-40 (EudraCT Number); U1111-1141-65868 (Other Identifier: (UTN))

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