Clinical trial NCT02004704: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sphingomyelin Lipidosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2013-12-09
Enrollment: 25
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study was to obtain data regarding the safety of olipudase alfa in participants with acid sphingomyelinase deficiency (ASMD) who were exposed to long term treatment with olipudase alfa.

The secondary objectives of this study were 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: LTS13632 is a multicenter, nonrandomized, open-label, long-term extension study of participants with ASMD who have previously participated in a study of olipudase alfa. (DFI13803 for pediatric participants and DFI13412 for adult participants).

The maximum study duration per participant was 9 years or until olipudase alfa becomes commercially accessible. Notwithstanding the above, every pediatric participant were treated in LTS13632 study for at least 3 years to comply with the requirements agreed in the olipudase alfa Pediatric Investigational Plan.

Eligibility criteria: Inclusion criteria:

* The participant 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 participant and/or the participant's parent(s)/legal guardian(s) was willing and able to provide signed written informed consent.
* The participant who is female and of childbearing potential must have had a negative urine pregnancy test for beta human chorionic gonadotropin (β HCG).
* Female participants of childbearing potential and sexually mature male participants must have been 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 participant had any new condition or worsening of an existing condition which in the opinion of the investigator would make the participant unsuitable for enrollment, or could interfere with the participation or completion the study.
* The participant, in the opinion of the investigator, was unable to adhere to the requirements of the study.
* The participant was 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 participant was unwilling or unable to avoid, for 10 days before and 3 days after liver biopsies, medications or herbal supplements that are potentially hepatotoxic (only participants who previously participated in the DFI13412 study).
* The participant required medication(s) that may decrease olipudase alfa activity (eg, fluoxetine, chlorpromazine; tricyclic antidepressants \[eg, imipramine, desipramine\]).

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

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs) Except Infusion-Associated Reactions (IARs)
timeFrame: From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first
measure: Number of Participants With IARs
timeFrame: From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first
measure: For Adults: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam
timeFrame: Baseline (Day 1 of original study), Month 78
measure: For Pediatrics: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam
timeFrame: Baseline (Day 1 of original study), Month 84
measure: For Adults: Number of Participants With Abnormality in Extended Neurological Examinations
timeFrame: Baseline (Day 1 of original study), Month 78
measure: For Pediatrics: Number of Participants With Abnormality in Extended Neurological Examinations
timeFrame: Baseline (Day 1 of original study), Month 84
measure: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs
timeFrame: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first
measure: Number of Participants With PCSA in Clinical Chemistry Parameters
timeFrame: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first
measure: Number of Participants With PCSA in Liver Function Tests
timeFrame: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first
measure: Number of Participants With PCSA in Hematology Parameters
timeFrame: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first
measure: Number of Participants With PCSA in Electrocardiogram (ECG)
timeFrame: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first
measure: For Adults: Percent Change From Baseline in Pre-Infusion Plasma Ceramide at Month 90
timeFrame: Baseline (Day 1 of original study) and Month 90 (pre-infusion)
measure: For Pediatrics: Percent Change From Baseline in Pre-Infusion Plasma Ceramide at Month 66
timeFrame: Baseline (Day 1 of original study) and Month 66 (pre-infusion)
measure: Participants From Adult Study DFI13412: Number of Participants With Abnormal Liver Biopsy
timeFrame: Baseline (Day 1 of original study) and Month 36
measure: Participants From Pediatric Study DFI13803: Number of Participants With Abnormalities in Liver Ultrasound Doppler
timeFrame: Baseline (Day 1 of original study), Week 2 and Months 12, 18 and 24
measure: Number of Participants With Anti-Drug Antibodies (ADA) Against Olipudase Alfa
timeFrame: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first
Secondary outcomes:
measure: Percent Change From Baseline in Spleen and Liver Volumes at Month 102 for Adults and Month 84 for Pediatrics
timeFrame: Baseline (Day 1 of original study), Month 102 for adults and Month 84 for pediatrics
measure: Change From Baseline in Pulmonary Imaging by High Resolution Computed Tomography (HRCT) at Month 102 for Adults and Month 84 for Pediatrics
timeFrame: Baseline (Day 1 of original study), Month 102 for adults and Month 84 for pediatrics
measure: Percent Change From Baseline in Percent Predicted Diffusing Capacity of Lungs For Carbon Monoxide (DLco) (Hemoglobin-Adjusted) at Month 78 for Adults and Month 84 for Pediatrics
timeFrame: Baseline (Day 1 of original study), Month 78 for adults and Month 84 for pediatrics
measure: Percent Change From Baseline in Platelet Count at Month 90 for Adults and Month 78 for Pediatrics
timeFrame: Baseline (Day 1 of original study), Month 90 for adults (pre-infusion) and Month 78 for pediatrics (pre-infusion)
measure: Percent Change From Baseline in Low-density Lipoprotein at Month 90 for Adults and Month 66 for Pediatrics
timeFrame: Baseline (Day 1 of original study), Month 90 for adults and Month 66 for pediatrics
measure: Participants From Adult Study DFI13412: Change From Baseline in Brief Fatigue Inventory (BFI) Questionnaire at Month 78
timeFrame: Baseline (Day 1 of original study) and Month 78
measure: Participants From Adult Study DFI13412: Change From Baseline in Brief Pain Inventory-Short Form (BPI-SF) Questionnaire at Month 78
timeFrame: Baseline (Day 1 of original study) and Month 78
measure: Participants From Adult Study DFI13412: Change From Baseline in Chronic Respiratory Disease Questionnaire Self-Administered Standardized (CRQ-SAS) at Month 78
timeFrame: Baseline (Day 1 of original study) and Month 78
measure: Participants From Pediatric Study DFI13803: Change From Baseline in Pediatric Quality of Life (PedsQL) Generic Core Total Scale Score at Month 72
timeFrame: Baseline (Day 1 of original study) and Month 72
measure: Participants From Pediatric Study DFI13803: Change From Baseline in Difference Between Bone Age and Actual Age of Participants at Month 72
timeFrame: Baseline (Day 1 of original study) and Month 72
measure: Participants From Pediatric Study DFI13803: Change From Baseline in Height Z-score at Month 72
timeFrame: Baseline (Day 1 of original study) and Month 72
Other outcomes:
Locations:
city: New York
country: United States
facility: Investigational Site Number 840001
state: New York
city: Leuven
country: Belgium
facility: Investigational Site Number 056001
city: Porto Alegre
country: Brazil
facility: Investigational Site Number 076001
city: Bron Cedex
country: France
facility: Investigational Site Number 250002
city: Hochheim Am Main
country: Germany
facility: Investigational Site Number 276002
city: Sassari
country: Italy
facility: Investigational Site Number 380002
city: Udine
country: Italy
facility: Investigational Site Number 380001
city: London
country: United Kingdom
facility: Investigational Site Number 826001
city: Manchester
country: United Kingdom
facility: Investigational Site Number 826002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
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.
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.