Efficacy, Safety, Pharmacodynamic, and Pharmacokinetics Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency (ASCEND)
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ClinicalTrials.gov Identifier: NCT02004691 |
Recruitment Status :
Active, not recruiting
First Posted : December 9, 2013
Last Update Posted : October 20, 2021
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Primary Objective:
The primary objective of this phase 2/3 study is to evaluate the efficacy of olipudase alfa (recombinant human acid sphingomyelinase) administered intravenously once every 2 weeks for 52 weeks in adult patients with acid sphingomyelinase deficiency (ASMD) by assessing changes in: 1) spleen volume as measured by abdominal magnetic resonance imaging (MRI) (and, for the United States [US] only, in association with patient perception related to spleen volume as measured by splenomegaly related score [SRS]); and 2) infiltrative lung disease as measured by the pulmonary function test, diffusing capacity of the lung for carbon monoxide (DLCO).
Secondary Objectives:
- To confirm the safety of olipudase alfa administered intravenously once every 2 weeks for 52 weeks.
- To characterize the effect of olipudase alfa on the patient perception related to spleen volume as measured by the SRS after 52 weeks of study drug administration. (For the US, the effect of olipudase alfa on the splenomegaly related score is part of the primary objective).
- To characterize the effect of olipudase alfa after 52 weeks of study drug administration on the following endpoints assessed sequentially:
- The effect of olipudase alfa on liver volume;
- The effect of olipudase alfa on platelet count;
- The effect of olipudase alfa on fatigue;
- The effect of olipudase alfa on pain;
- The effect of olipudase alfa on dyspnea.
Condition or disease | Intervention/treatment | Phase |
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Sphingomyelin Lipidosis | Drug: placebo (saline) Drug: GZ402665 | Phase 2 Phase 3 |
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 36 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Primary Purpose: | Treatment |
Official Title: | A Phase 2/3, Multicenter, Randomized, Double-blinded, Placebo-controlled, Repeat-dose Study to Evaluate the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency |
Actual Study Start Date : | December 18, 2015 |
Actual Primary Completion Date : | October 17, 2019 |
Estimated Study Completion Date : | October 2023 |

Arm | Intervention/treatment |
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Experimental: GZ402665
Olipudase alfa dose (3 mg/kg body weight) in saline administered intravenously once every 2 weeks during the 52 weeks of the primary analysis period for patients randomized to olipudase alfa, and during the extension treatment period for all patients.
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Drug: GZ402665
Pharmaceutical form: Powder for concentrate for solution for infusion administered once every two weeks during the 52 weeks of the primary analysis period for patients randomized to olipudase alfa, and during the extension treatment period for all patients. Route of administration: intravenous infusion Other Name: olipudase alfa |
Placebo Comparator: Placebo
Placebo (saline) administered intravenously once every 2 weeks during the 52 weeks of the primary analysis period for patients randomized to placebo.
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Drug: placebo (saline)
Pharmaceutical form: solution administered once every two weeks during the 52 weeks of the primary analysis period for patients randomized to placebo. Route of administration: intravenous infusion |
- Percentage change in spleen volume (combined with change in SRS in the US only, and referred to as "combination spleen endpoint") [ Time Frame: Baseline to Week 52 ]
- Percentage change in diffusing capacity of the lung for carbon monoxide [ Time Frame: Baseline to Week 52 ]
- Percentage change in liver volume [ Time Frame: Baseline to Week 52 ]
- Percentage change in platelet count [ Time Frame: Baseline to Week 52 ]
- Change in fatigue severity as measured by item 3 of the Brief Fatigue Inventory scale [ Time Frame: Baseline to Week 52 ]
- Change in pain severity as measured by item 3 of the Brief Pain Inventory scale [ Time Frame: Baseline to Week 52 ]
- Change in dyspnea severity as measured by the Functional Assessment of Chronic Illness Therapy dyspnea tool [ Time Frame: Baseline to Week 52 ]
- Change in SRS (except US, where it is part of the primary "combination spleen endpoint") [ Time Frame: Baseline to Week 52 ]
- Number of adverse events [ Time Frame: Baseline to approximately 5 years ]

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion criteria :
- The patient is willing and able to provide signed written informed consent.
- The patient is male or female aged 18 years or older.
- The patient has documented deficiency of acid sphingomyelinase as measured in peripheral leukocytes, cultured fibroblasts, or lymphocytes; and a clinical diagnosis consistent with Niemann-Pick disease type B (NPD B).
- The patient has diffuse capacity of the lung for carbon monoxide ≤70% of the predicted normal value.
- The patient has a spleen volume ≥6 multiples of normal (MN) measured by MRI; patients who have had partial splenectomy will be allowed if the procedure was performed ≥1 year before screening/baseline and the residual spleen volume is ≥6 MN.
- The patient has a mean SRS of at least 5.
- Female patients of childbearing potential must have a negative serum pregnancy test for beta-human chorionic gonadotropin (β-HCG).
- Female patients of childbearing potential and 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 for up to 15 days following their last dose of study drug.
Exclusion criteria:
- The patient has received an investigational drug within 30 days before study enrollment.
- The patient has a medical condition, including significant intercurrent illness; significant cardiac disease (e.g., clinically significant arrhythmia, moderate or severe pulmonary hypertension or clinically significant valve dysfunction, or <40% left ventricular ejection fraction by echocardiogram); active hepatitis B or hepatitis C, or infection with human immunodeficiency virus (HIV); malignancy diagnosed within the past 5 years (other than non-melanoma skin cancer), or any other serious medical condition that may preclude participation in the study.
- The patient has a platelet count <60,000/μL based on the average of 2 samples.
- The patient has an international normalized ratio (INR) >1.5.
- The patient has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >250 IU/L or total bilirubin >1.5 mg/dL (except for patients with Gilbert's syndrome).
- The patient has had a major organ transplant (eg, bone marrow or liver).
- The patient is scheduled during the study for in-patient hospitalization including elective surgery and excluding the liver biopsies required per protocol.
- 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 before and 3 days after each study drug infusion. Testing for blood alcohol levels will not be required.
- The patient is unwilling or unable to avoid 10 days before and 3 days after the protocol scheduled liver biopsies the use of medications or herbal supplements that are potentially hepatotoxic (eg, 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitors, erythromycin, valproic acid, anti-depressants, kava, echinacea) and/or may cause or prolong bleeding (eg, anti-coagulants, ibuprofen, aspirin, garlic supplements, ginkgo, ginseng).
- The patient requires medications that may decrease olipudase alfa activity (eg, fluoxetine, chlorpromazine, tricyclic antidepressants [eg, imipramine, or desipramine]).
- The patient requires use of invasive ventilatory support.
- The patient requires use of noninvasive ventilator support while awake for longer than 12 hours daily.
- The patient is breast-feeding.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02004691

Study Director: | Clinical Sciences & Operations | Sanofi |
Responsible Party: | Genzyme, a Sanofi Company |
ClinicalTrials.gov Identifier: | NCT02004691 |
Other Study ID Numbers: |
DFI12712 2015-000371-26 ( EudraCT Number ) U1111-1142-5963 ( Other Identifier: UTN ) |
First Posted: | December 9, 2013 Key Record Dates |
Last Update Posted: | October 20, 2021 |
Last Verified: | October 19, 2021 |
Niemann-Pick Disease, Type A Niemann-Pick Diseases Niemann-Pick Disease, Type C Lipidoses Sphingolipidoses Lysosomal Storage Diseases, Nervous System Brain Diseases, Metabolic, Inborn Brain Diseases, Metabolic Brain Diseases Central Nervous System Diseases |
Nervous System Diseases Histiocytosis, Non-Langerhans-Cell Histiocytosis Lymphatic Diseases Metabolism, Inborn Errors Genetic Diseases, Inborn Lipid Metabolism, Inborn Errors Lysosomal Storage Diseases Metabolic Diseases Lipid Metabolism Disorders |