search
Back to results

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

Primary Purpose

Sphingomyelin Lipidosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
GZ402665
Sponsored by
Genzyme, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sphingomyelin Lipidosis

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number 840001
  • Investigational Site Number 056001
  • Investigational Site Number 076001
  • Investigational Site Number 250002
  • Investigational Site Number 276002
  • Investigational Site Number 380002
  • Investigational Site Number 380001
  • Investigational Site Number 826001
  • Investigational Site Number 826002

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GZ402665

Arm Description

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.

Outcomes

Primary Outcome Measures

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
Complete physical examinations including extended neurologic and abbreviated physical exams
Vital signs, electrocardiograms and echocardiograms with Doppler
Clinical laboratory tests
Safety biomarkers
Liver biopsy (patients previously enrolled in DFI13412)
Liver ultrasound/Doppler (patients previously enrolled in DFI13803)
Immune response assessments

Secondary Outcome Measures

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

Full Information

First Posted
November 26, 2013
Last Updated
September 22, 2023
Sponsor
Genzyme, a Sanofi Company
search

1. Study Identification

Unique Protocol Identification Number
NCT02004704
Brief Title
A Long-Term Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency
Official Title
A Long-Term Study to Assess the Ongoing Safety and Efficacy of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
December 4, 2013 (Actual)
Primary Completion Date
September 6, 2023 (Actual)
Study Completion Date
September 6, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sphingomyelin Lipidosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GZ402665
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
GZ402665
Other Intervention Name(s)
Olipudase alfa
Intervention Description
Pharmaceutical form: Powder for concentrate for solution for infusion Route of administration: intravenous infusion
Primary Outcome Measure Information:
Title
Adverse events (AEs)/treatment-emergent adverse events (TEAEs), including infusion-associated reactions and adverse events of special interest (AESIs)
Description
Number of patients experiencing AEs, TEAEs, or AESIs
Time Frame
Baseline to up to 9 years
Title
Complete physical examinations including extended neurologic and abbreviated physical exams
Time Frame
Baseline to up to 9 years
Title
Vital signs, electrocardiograms and echocardiograms with Doppler
Time Frame
Baseline to up to 9 years
Title
Clinical laboratory tests
Time Frame
Baseline to up to 9 years
Title
Safety biomarkers
Time Frame
Baseline to up to 9 years
Title
Liver biopsy (patients previously enrolled in DFI13412)
Time Frame
Baseline to after at least 3 years in the study
Title
Liver ultrasound/Doppler (patients previously enrolled in DFI13803)
Time Frame
Baseline to 5 years
Title
Immune response assessments
Time Frame
Baseline to up to 9 years
Secondary Outcome Measure Information:
Title
Spleen and liver volume
Description
Abdominal magnetic resonance imaging (MRI) to evaluate improvements in spleen and liver volume
Time Frame
Baseline to up to 9 years
Title
Pulmonary imaging
Time Frame
Baseline to up to 9 years
Title
Pulmonary function test
Time Frame
Baseline to up to 9 years
Title
Hematology
Description
(hemoglobin and platelet count)
Time Frame
Baseline to up to 9 years
Title
Lipid profile
Time Frame
Baseline to up to 9 years
Title
Health outcome questionnaires (adults and pediatric)
Time Frame
Baseline to up to 9 years
Title
Hand X ray for bone age and bone maturation (pediatric patients)
Time Frame
Baseline to up to 9 years
Title
Linear patient growth by height Z -score (pediatric patients)
Time Frame
Baseline to up to 9 years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 840001
City
New York
State/Province
New York
ZIP/Postal Code
10029-6574
Country
United States
Facility Name
Investigational Site Number 056001
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Investigational Site Number 076001
City
Porto Alegre
ZIP/Postal Code
90035 003
Country
Brazil
Facility Name
Investigational Site Number 250002
City
Bron Cedex
ZIP/Postal Code
69677
Country
France
Facility Name
Investigational Site Number 276002
City
Hochheim Am Main
ZIP/Postal Code
65239
Country
Germany
Facility Name
Investigational Site Number 380002
City
Sassari
ZIP/Postal Code
07100
Country
Italy
Facility Name
Investigational Site Number 380001
City
Udine
ZIP/Postal Code
33100
Country
Italy
Facility Name
Investigational Site Number 826001
City
London
ZIP/Postal Code
WC1N 3JZ
Country
United Kingdom
Facility Name
Investigational Site Number 826002
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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
Citations:
PubMed Identifier
32620536
Citation
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.
Results Reference
derived
PubMed Identifier
29305734
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs