Phase 2
N=25
A Long-Term Study of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency
Sphingomyelin Lipidosis
Bottom Line
View on ClinicalTrials.gov: NCT02004704 ↗Enrolled (actual)
25
Serious AEs
44.0%
Results posted
Jul 2024
Primary outcome: Primary: 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) — 5; 20; 1; 10 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- GZ402665 (Drug)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Genzyme, a Sanofi Company
- Primary completion
- Sep 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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) |
5; 20; 1; 10; 0; 0 | — |
| PRIMARY Number of Participants With IARs |
4; 13; 5; 20 | — |
| PRIMARY For Adults: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam |
0; 0; 1; 1; 0; 0 | — |
| PRIMARY For Pediatrics: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam |
0; 1; 0; 0; 0; 0 | — |
| PRIMARY For Adults: Number of Participants With Abnormality in Extended Neurological Examinations |
— | — |
| PRIMARY For Pediatrics: Number of Participants With Abnormality in Extended Neurological Examinations |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs |
1; 9; 2; 10; 2; 16 | — |
| PRIMARY Number of Participants With PCSA in Clinical Chemistry Parameters |
0; 0; 1; 4; 0; 15 | — |
| PRIMARY Number of Participants With PCSA in Liver Function Tests |
0; 5; 0; 6; 0; 5 | — |
| PRIMARY Number of Participants With PCSA in Hematology Parameters |
2; 16; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With PCSA in Electrocardiogram (ECG) |
0; 3; 1; 2; 0; 6 | — |
| PRIMARY For Adults: Percent Change From Baseline in Pre-Infusion Plasma Ceramide at Month 90 |
-65.66 | — |
| PRIMARY For Pediatrics: Percent Change From Baseline in Pre-Infusion Plasma Ceramide at Month 66 |
-69.16 | — |
| PRIMARY Participants From Adult Study DFI13412: Number of Participants With Abnormal Liver Biopsy |
1; 1; 2; 1; 0; 0 | — |
| PRIMARY Participants From Pediatric Study DFI13803: Number of Participants With Abnormalities in Liver Ultrasound Doppler |
6; 3; 1; 0; 5; 0 | — |
| PRIMARY Number of Participants With Anti-Drug Antibodies (ADA) Against Olipudase Alfa |
0; 2; 0; 1; 3; 14 | — |
| SECONDARY Percent Change From Baseline in Spleen and Liver Volumes at Month 102 for Adults and Month 84 for Pediatrics |
-63.60; -75.56; -46.71; -59.55 | — |
| SECONDARY Change From Baseline in Pulmonary Imaging by High Resolution Computed Tomography (HRCT) at Month 102 for Adults and Month 84 for Pediatrics |
-1.21; -0.42; -1.66; -1.35; 0; 0 | — |
| SECONDARY 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 |
55.29; 46.20 | — |
| SECONDARY Percent Change From Baseline in Platelet Count at Month 90 for Adults and Month 78 for Pediatrics |
21.83; 63.97 | — |
| SECONDARY Percent Change From Baseline in Low-density Lipoprotein at Month 90 for Adults and Month 66 for Pediatrics |
-24.51; -37.30 | — |
| SECONDARY Participants From Adult Study DFI13412: Change From Baseline in Brief Fatigue Inventory (BFI) Questionnaire at Month 78 |
-0.9; 0.6 | — |
| SECONDARY Participants From Adult Study DFI13412: Change From Baseline in Brief Pain Inventory-Short Form (BPI-SF) Questionnaire at Month 78 |
-1.5; 0.7 | — |
| SECONDARY Participants From Adult Study DFI13412: Change From Baseline in Chronic Respiratory Disease Questionnaire Self-Administered Standardized (CRQ-SAS) at Month 78 |
0.3; 0.2; 0.3; -0.5 | — |
| SECONDARY Participants From Pediatric Study DFI13803: Change From Baseline in Pediatric Quality of Life (PedsQL) Generic Core Total Scale Score at Month 72 |
10.4; 14.6 | — |
| SECONDARY Participants From Pediatric Study DFI13803: Change From Baseline in Difference Between Bone Age and Actual Age of Participants at Month 72 |
28.34 | — |
| SECONDARY Participants From Pediatric Study DFI13803: Change From Baseline in Height Z-score at Month 72 |
2.31 | — |
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.
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.
Data sourced from ClinicalTrials.gov (NCT02004704). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.