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Outcome Measures

Primary Outcomes (16)

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)
An AE: Any untoward medical occurrence in participant or clinical investigation participant administered with pharmaceutical product, which did not necessarily have to have causal relationship with study treatment. SAEs: Any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization/prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect, was medically important event. TEAEs: AEs that started during on-treatment period-either in this study or in original study which were ongoing at the time the participant signed the written informed consent. An AESI: AE (serious or nonserious) of scientific and medical concern specific to sponsor's product or program, for which ongoing monitoring and rapid communication by investigator to sponsor was appropriate.
From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first
Number of Participants With IARs
Protocol-defined IARs were AEs that occurred during the infusion or within up to 24 hours after the start of infusion and were considered as related or possibly related to the study treatment by the investigator or the sponsor. Events occurring greater than or equal to (\>=) 24 hours after the start of an infusion might have been judged an IAR at the discretion of the investigator or sponsor. Algorithm-defined IARs were all AEs that started between the start of infusion and the end of infusion plus 24 hours, irrespective of the perceived relation with study treatment.
From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first
For Adults: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam
A complete physical examination included assessment of the participant's general appearance, general neurological status, skin, head, eyes, ears, nose, throat, lymph nodes, heart, lungs, abdomen, and extremities/joints. Shift from Baseline was monitored. An abbreviated physical exam (general appearance only) was only performed pre- and post-infusion for those who did not do complete exam.
Baseline (Day 1 of original study), Month 78
For Pediatrics: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam
A complete physical examination included assessment of the participant's general appearance, skin, head, eyes, ears, nose, throat, lymph nodes, heart, lungs, abdomen, and extremities/joints. Shift from Baseline was monitored. An abbreviated physical exam (general appearance only) was only performed pre- and post-infusion for those who did not do complete exam.
Baseline (Day 1 of original study), Month 84
For Adults: Number of Participants With Abnormality in Extended Neurological Examinations
Extended neurological examination for adults included examination of mental status. Shift from Baseline was monitored.
Baseline (Day 1 of original study), Month 78
For Pediatrics: Number of Participants With Abnormality in Extended Neurological Examinations
The neurological examination in pediatric participants included examination of mental status, cranial nerve examination, motor examination: tone, reflexes examination, sensory examination, coordination, gait and coordination, and strength examination. Shift from Baseline was monitored.
Baseline (Day 1 of original study), Month 84
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs
PCSA: Heart Rate: High: \>=120 beats per minute (bpm) (adults \[ad\], adolescents \[ado\], children \[chi\]), \>=140 bpm (early chi \[ec\]), \>=175 bpm (infants\[inf\]) \& increase from baseline (IFB)\>=20 bpm for all age ranges (AAR), HR Low: \<=50 bpm (ad, ado, chi), \<=75 bpm (ec), \<=80 bpm (inf) \& decrease from baseline (DFB) \>=20 bpm for AAR. Systolic blood pressure: High: \>= 160 millimeters of mercury (mmHg) (ad); \>=119 mmHg (ado), \>=108 mmHg (chi), \>=101 mmHg (ec),\>=98 mmHg (inf) \& IFB \>=20 mmHg for AAR. SBP Low: \<=95 mmHg (ad), \<=90 mmHg (ado), \<= 80mm Hg (chi), \<=70 mmHg (ec), \<=70 mmHg (inf) \& DFB \>=20 mmHg for AAR. Diastolic blood pressure: High:\>110 mmHg (ad), \>=78 mmHg (ado), \>=72 mmHg (chi), \>=59 mmHg (ec), \>=54 mmHg (inf) and IFB \>=10 mmHg for AAR. DBP Low:\<=45 mmHg (ad), \<=54 mmHg (ado), \<=48 mmHg (chi), \<=34mmHg (ec and inf) \& DFB\>=10 mmHg for AAR.
Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first
Number of Participants With PCSA in Clinical Chemistry Parameters
PCSA: Creatinine High, category 1: \>=150 micromole/L (umol) (adults), \>=132 umol/L or 1.5 mg/deciliter (dL) (adolescents), \>=90 umol/litre (L) or 1.1 mg/dL (children), \>53 umol/L or 0.6 mg/dL (early children and infants); category 2: \>=30% IFB (adults). Blood Urea Nitrogen: \>=17 millimole (mmol)/L (adults), \>=6.4 mmol/L or 18 mg/dL (pediatrics \[ped\]). Glucose Low\<=3.9 mmol/L and \<lower limit of normal (adults), \<2.7 mmol/L (ped), High: \>=11.1 mmol/L (unfasted), \>7 mmol/L (fasted) (adults), \>=7 mmol/L (fasted after \>12 hours of fast); \>=10.0 mmol/L (unfasted) (ped).
Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first
Number of Participants With PCSA in Liver Function Tests
PCSA: Alanine aminotransferase (ALT) \>3 x upper limit of normal (ULN). Aspartate aminotransferase (AST) \>3 x ULN. Alkaline phosphatase (ALP) \> 1.5 x ULN. Total Bilirubin \>1.5 x ULN (ad) and \>1.3 x ULN (ped). ALT and total bilirubin: ALT \> 3 x ULN and total bilirubin \> 2 x ULN.
Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first
Number of Participants With PCSA in Hematology Parameters
PCSA: White blood cells (WBC): Low: \<3.0 Giga (G)/L (Non-Black \[NB\])/\<2.0 G/L (Black \[B\])(ad), \<4.5 G/L (ado), \<5.0 G/L(chi), \<3.0 G/L (ec), \<4.0 G/L (inf), High: \>=16.0 G/L(ad), \>13.5 G/L (ado), \>17.0 G/L(chi), \>16 G/L (ec), \>20 G/L (inf). Hemoglobin-ad: Low-1: \<=115 g/dL (Male \[M\])/\<=95 g/dL (Female \[F\]), 20% DFB for both, High:\>=185 g/L (M)/\>=165 g/L (F), Low-2: DFB\>=20 g/L (ad), \<10 g/dL (ado, chi, ec); \<9.0 g/dL (inf); 20% DFB for all. Platelets: Low: \<100 G/L (AAR) and 20% DFB and High: \>=700 G/L (ad and ped).
Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first
Number of Participants With PCSA in Electrocardiogram (ECG)
PCSA: Heart rate: High:\>=120 bpm (ad, ado, chi), \>=140 bpm (ec), \>=175 bpm (inf) \& IFB\>=20 bpm for AAR, Heart rate: Low: \<=50 bpm (ad, ado, chi), \<=75 bpm (ec), \<=80 bpm (inf) \& DFB \>=20 bpm for AAR. PR duration: High: \>=200 milliseconds (ms) (ad) and IFB\>=20 ms, \>180 ms (ado), 170 ms (chi), 160 ms (ec), and 140 ms (inf). QT correction-Bazett (QTcB): Borderline absolute (category 1): 431-450 ms (ad and ado M, chi, ec and inf), 451-470 ms (ad and ado F), Prolonged-absolute (category 2): \>450 ms (ad and ado M and chi, ec and inf), \>470 ms (ad and ado F), Additional-absolute (category 3): \>=500 ms (AAR), Borderline increase (category 4): 30-60 ms (AAR), Prolonged increase (category 5): \> 60 ms (AAR).
Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first
For Adults: Percent Change From Baseline in Pre-Infusion Plasma Ceramide at Month 90
Plasma samples were collected to evaluate ceramide levels for safety biomarker analysis. Baseline was defined as the last available non-missing value prior to the first infusion in original study.
Baseline (Day 1 of original study) and Month 90 (pre-infusion)
For Pediatrics: Percent Change From Baseline in Pre-Infusion Plasma Ceramide at Month 66
Plasma samples were collected to evaluate ceramide levels for safety biomarker analysis. Baseline was defined as the last available non-missing value prior to the first infusion in original study.
Baseline (Day 1 of original study) and Month 66 (pre-infusion)
Participants From Adult Study DFI13412: Number of Participants With Abnormal Liver Biopsy
Liver biopsy samples were evaluated for sphingomyelin accumulation and liver pathology in the participants who previously participated in the DFI13412 study who were at least 18 years old when they entered in this study. Sphingomyelin accumulation was quantified in liver by computer morphometry of high-resolution light microscopy images. Fibrosis grading was assessed on the Laennec scoring system, which grades the extent of fibrosis on a scale from 0 to 4 (0=none; 1=minimal; 2=mild; 3=moderate; 4=cirrhosis). Higher score indicated more severity.
Baseline (Day 1 of original study) and Month 36
Participants From Pediatric Study DFI13803: Number of Participants With Abnormalities in Liver Ultrasound Doppler
Liver ultrasound doppler was performed for pediatric participants transitioning from DFI13803 to document hepatic blood flow characteristics, principally portal vein pressure, and blood flow direction. The parameters evaluated were liver dysmorphic findings, liver surface abnormalities, mild ascites and hepatic steatosis. Liver ultrasound Doppler was performed using methods that were compatible with the standard institutional procedures of the investigational site.
Baseline (Day 1 of original study), Week 2 and Months 12, 18 and 24
Number of Participants With Anti-Drug Antibodies (ADA) Against Olipudase Alfa
Blood samples were collected for the presence of ADAs against olipudase alfa. Treatment-boosted ADA: Positive ADA status positive at baseline (pre-existing ADA) and ADA titer level anytime post-baseline significantly higher than that at baseline. Transient ADA: Treatment-induced ADA detected only at 1 sampling time point post-baseline and treatment-induced ADA detected at 2 or more sampling time points post-baseline, where first and last ADA-positive samples (irrespective of any negative samples in between) separated by period of less than 16 weeks, and participant's last sampling time point was ADA-negative. Persistent ADA response: Treatment-induced ADA detected at 2 or more sampling time points post-baseline, where first and the last ADA-positive on-treatment sample (irrespective of any negative samples in between) separated by at least 16 weeks. Treatment-induced: ADA detected in the last 2 sampling time points, irrespective of the time period in between.
Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first

Secondary Outcomes (11)

Percent Change From Baseline in Spleen and Liver Volumes at Month 102 for Adults and Month 84 for Pediatrics
Baseline (Day 1 of original study), Month 102 for adults and Month 84 for pediatrics
Change From Baseline in Pulmonary Imaging by High Resolution Computed Tomography (HRCT) at Month 102 for Adults and Month 84 for Pediatrics
Baseline (Day 1 of original study), Month 102 for adults and Month 84 for pediatrics
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
Baseline (Day 1 of original study), Month 78 for adults and Month 84 for pediatrics
Percent Change From Baseline in Platelet Count at Month 90 for Adults and Month 78 for Pediatrics
Baseline (Day 1 of original study), Month 90 for adults (pre-infusion) and Month 78 for pediatrics (pre-infusion)
Percent Change From Baseline in Low-density Lipoprotein at Month 90 for Adults and Month 66 for Pediatrics
Baseline (Day 1 of original study), Month 90 for adults and Month 66 for pediatrics

Study Arms (1)

GZ402665

EXPERIMENTAL

GZ402665 administered intravenously once every 2 weeks at the dose each participant 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 participant decides to enter another olipudase alfa clinical trial within the 9-year period prior to when olipudase alfa is commercially accessible.

Drug: GZ402665

Eligibility Criteria

Sexall

Healthy VolunteersNo

Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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.

Study Sites (9)

Investigational Site Number 840001

New York, New York, 10029-6574, United States

Investigational Site Number 056001

Leuven, 3000, Belgium

Investigational Site Number 076001

Porto Alegre, 90035 003, Brazil

Investigational Site Number 250002

Bron, 69677, France

Investigational Site Number 276002

Hochheim am Main, 65239, Germany

Investigational Site Number 380002

Sassari, 07100, Italy

Investigational Site Number 380001

Udine, 33100, Italy

Related Publications (4)

Scarpa M, Diaz GA, Giugliani R, Jones SA, Mengel E, Guffon N, Witters P, Ganesh J, Armstrong NM, Srivastava S, Kim Y. Long-Term Safety and Clinical Outcomes With Olipudase Alfa Enzyme Replacement Therapy in Children and Adolescents With Acid Sphingomyelinase Deficiency. J Inherit Metab Dis. 2025 Sep;48(5):e70086. doi: 10.1002/jimd.70086.

PMID: 40937531DERIVED

Lachmann RH, Diaz GA, Wasserstein MP, Armstrong NM, Yarramaneni A, Kim Y, Kumar M. Olipudase alfa enzyme replacement therapy for acid sphingomyelinase deficiency (ASMD): sustained improvements in clinical outcomes after 6.5 years of treatment in adults. Orphanet J Rare Dis. 2023 Apr 25;18(1):94. doi: 10.1186/s13023-023-02700-x.

PMID: 37098529DERIVED

MeSH Terms

Conditions

Niemann-Pick Disease, Type A

Interventions

olipudase alfa

Condition Hierarchy (Ancestors)

Niemann-Pick DiseasesSphingolipidosesLysosomal Storage Diseases, Nervous SystemBrain Diseases, Metabolic, InbornBrain Diseases, MetabolicBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesHistiocytosis, Non-Langerhans-CellHistiocytosisLymphatic DiseasesHemic and Lymphatic Diseases

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

Brief Summary

Registry Overview

Trial Relationships

Study Timeline

First Submitted

Study Start

First Posted

Primary Completion

Study Completion

Results Posted

Conditions

Outcome Measures

Primary Outcomes (16)

Secondary Outcomes (11)

Study Arms (1)

GZ402665

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (9)

Related Publications (4)

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Results Point of Contact

Study Officials

Publication Agreements

Enrollment

Study Design

Study Record Dates

You may not qualify if:

Data Sharing

Source record

Documents

Locations

Brief Summary

Registry Overview

Trial Relationships

Related Scientific Literature

Study Timeline

First Submitted

Study Start

First Posted

Primary Completion

Study Completion

Results Posted

Conditions

Outcome Measures

Primary Outcomes (16)

Secondary Outcomes (11)

Study Arms (1)

GZ402665

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (9)

Related Publications (4)

MeSH Terms

Conditions

Interventions

Condition Hierarchy (Ancestors)

Results Point of Contact

Study Officials

Publication Agreements

Enrollment

Study Design

Study Record Dates

You may not qualify if:

Data Sharing

Source record

Documents

Locations