A Long-Term Study to Assess the Ongoing Safety and Efficacy of Olipudase Alfa in Patients With Acid Sphingomyelinase Deficiency

Number of Participants With PCSA in Hematology Parameters

时间窗: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first

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).

Participants From Pediatric Study DFI13803: Number of Participants With Abnormalities in Liver Ultrasound Doppler

时间窗: Baseline (Day 1 of original study), Week 2 and Months 12, 18 and 24

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.

For Adults: Percent Change From Baseline in Pre-Infusion Plasma Ceramide at Month 90

时间窗: Baseline (Day 1 of original study) and Month 90 (pre-infusion)

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.

Participants From Adult Study DFI13412: Number of Participants With Abnormal Liver Biopsy

时间窗: Baseline (Day 1 of original study) and Month 36

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.

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)

时间窗: From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first

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.

For Pediatrics: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam

时间窗: Baseline (Day 1 of original study), Month 84

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.

Number of Participants With PCSA in Electrocardiogram (ECG)

时间窗: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first

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).

Number of Participants With IARs

时间窗: From the signature of informed consent up to 9 years or until olipudase alfa was commercially accessible, whichever came first

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.

For Adults: Number of Participants With Abnormality in Complete Physical Examinations Including Abbreviated Physical Exam

时间窗: Baseline (Day 1 of original study), Month 78

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.

For Adults: Number of Participants With Abnormality in Extended Neurological Examinations

时间窗: Baseline (Day 1 of original study), Month 78

Extended neurological examination for adults included examination of mental status. Shift from Baseline was monitored.

For Pediatrics: Number of Participants With Abnormality in Extended Neurological Examinations

时间窗: Baseline (Day 1 of original study), Month 84

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.

Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Vital Signs

时间窗: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first

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.

Number of Participants With PCSA in Clinical Chemistry Parameters

时间窗: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first

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).

Number of Participants With PCSA in Liver Function Tests

时间窗: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first

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.

For Pediatrics: Percent Change From Baseline in Pre-Infusion Plasma Ceramide at Month 66

时间窗: Baseline (Day 1 of original study) and Month 66 (pre-infusion)

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.

Number of Participants With Anti-Drug Antibodies (ADA) Against Olipudase Alfa

时间窗: Baseline (Day 1 of original study) up to 9 years or until olipudase alfa was commercially accessible, whichever came first

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.