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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Sphingomyelin Lipidosis

Intervention / Treatment
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* Drug: GZ402665


Participation Criteria
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Eligibility Criteria
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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.
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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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GZ402665<br>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<br>* Pharmaceutical form: Powder for concentrate for solution for infusion Route of administration: intravenous infusion<br>* Other names: Olipudase alfa;|

What is the study measuring?
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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 |