Safety, Tolerability, PK, and Efficacy Evaluation of Repe... | NCT02292654

ID	Type	Description	Link
U1111-1160-6469	Other Identifier	UTN

Label	Type	Description	Intervention Names
Olipudase alfa	Experimental	Participants received intravenous (IV) infusion of olipudase alfa once every 2 weeks (Q2W) for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 milligram per kilogram (mg/kg). Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.	Drug: Olipudase alfa

Name	Type	Description	Arm Group Labels	Other Names
Olipudase alfa	Drug	Pharmaceutical form: powder for concentrate for solution for infusion Route of administration: intravenous infusion	Olipudase alfa

Measure	Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	TEAEs were defined as adverse events (AEs) that occurred or worsened during the on-treatment period (time from the start of investigational medicinal product [IMP]) administration until end of study (i.e. up to 64 weeks).	From Baseline up to End of study (64 weeks)
Number of Participants With Infusion-Associated Reactions (IARs)	IARs were defined as 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. Protocol-defined IAR: all AEs that were identified as an IAR by the investigator. Events occurring greater than or equal to (>=) 24 hours after the start of an infusion might had been judged an IAR at the discretion of the investigator or sponsor.	Within up to 24 hours after start of any infusion (during the treatment period i.e. from Baseline up to 64 weeks)
Number of Participants With Change in Physical Examination	Change from Normal assessment (at Baseline) to Abnormal assessment (at Week 52) was reported. Physical examinations included following observations/measurements: examination of the skin, head, eyes, ears, nose, and throat; lymph nodes; heart, lungs, and abdomen; extremities and joints. Abnormality in physical examinations was based on investigator's discretion.	Baseline, Week 52 (last complete assessment)
Number of Participants With Change in Neurological Examination	Change from Normal assessment (at Baseline) to Abnormal assessment (at Week 52) was reported. Neurological examination included: coordination examination, cranial nerve examination, extrapyramidal features, fundoscopy, gait and coordination examination, motor examination, tone peripheral nervous system, reflexes examination, sensory examination, strength examination, mental status.	Baseline, Week 52 (last assessment)

Measure	Description	Time Frame
Pharmacokinetic (PK) Parameter: Plasma Concentration of Olipudase Alfa at the End of Infusion (Ceoi)	Ceoi was defined as the plasma concentration at the end of infusion (EOI). Data collected for child and Infant/child age groups at 0-30 min from end of infusion was considered at end of infusion.	At the end of infusion of the first 3.0 mg/kg dose and at Week 52

Name	Affiliation	Role
Clinical Sciences & Operations	Sanofi	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Investigational Site Number 840001		New York	New York	10029	United States
Investigational Site Number 076001

PubMed Identifier	Type	Citation	Retractions
33875845	Derived	Diaz GA, Jones SA, Scarpa M, Mengel KE, Giugliani R, Guffon N, Batsu I, Fraser PA, Li J, Zhang Q, Ortemann-Renon C. One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency. Genet Med. 2021 Aug;23(8):1543-1550. doi: 10.1038/s41436-021-01156-3. Epub 2021 Apr 19.

ID	Title	Description
FG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to less than (<) 18 years received intravenous (IV) infusion of olipudase alfa once every 2 weeks (Q2W) for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 milligram per kilogram (mg/kg). Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Aug 21, 2017	Nov 30, 2020

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

TEAEs were defined as adverse events (AEs) that occurred or worsened during the on-treatment period (time from the start of investigational medicinal product [IMP]) administration until end of study (i.e. up to 64 weeks).

Safety population included all participants who received at least 1 infusion (partial or total) of olipudase alfa.

Posted

Count of Participants

Participants

From Baseline up to End of study (64 weeks)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort	Participants aged <6 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG003	Total Participants	All participants received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. The target maintenance dose was 3.0 mg/kg, which was maintained for the remaining duration of 64 treatment weeks.

Units	Counts
Participants	OG0004 OG0019 OG0027 OG003

Title

Denominators

Categories

Any TEAEs

Title	Measurements
	OG0004 OG0019 OG0027 OG003

Primary

Number of Participants With Infusion-Associated Reactions (IARs)

IARs were defined as 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. Protocol-defined IAR: all AEs that were identified as an IAR by the investigator. Events occurring greater than or equal to (>=) 24 hours after the start of an infusion might had been judged an IAR at the discretion of the investigator or sponsor.

Analysis was performed on safety population.

Posted

Count of Participants

Participants

Within up to 24 hours after start of any infusion (during the treatment period i.e. from Baseline up to 64 weeks)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3,0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Primary

Number of Participants With Change in Physical Examination

Change from Normal assessment (at Baseline) to Abnormal assessment (at Week 52) was reported. Physical examinations included following observations/measurements: examination of the skin, head, eyes, ears, nose, and throat; lymph nodes; heart, lungs, and abdomen; extremities and joints. Abnormality in physical examinations was based on investigator's discretion.

Analysis was performed on safety population. One participant may be counted in multiple categories.

Posted

Count of Participants

Participants

Baseline, Week 52 (last complete assessment)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Primary

Number of Participants With Change in Neurological Examination

Change from Normal assessment (at Baseline) to Abnormal assessment (at Week 52) was reported. Neurological examination included: coordination examination, cranial nerve examination, extrapyramidal features, fundoscopy, gait and coordination examination, motor examination, tone peripheral nervous system, reflexes examination, sensory examination, strength examination, mental status.

Analysis was performed on safety population. One participant may be counted in multiple categories.

Posted

Count of Participants

Participants

Baseline, Week 52 (last assessment)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Primary

Number of Participants With Abnormal Liver Function Laboratory Values at the End of Study

Abnormal values in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and alkaline phosphatase were reported.

Analysis was performed on safety population. One participant may be counted in multiple categories.

Posted

Count of Participants

Participants

At End of Study (Week 64)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort

Primary

Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities

Heart Rate (HR) High: >=120 beats per minute (bpm) (adolescents), >=120 bpm (children), >=140 bpm (early children), >=175 bpm (infants) & increase from baseline (IFB) >=20 bpm for all age categories.
HR Low: <=50 bpm (adolescents), <=50 bpm (children), <=75 bpm (early children), <=80 bpm (infants) & decrease from baseline (DFB) >=20 bpm for all age categories.
Systolic BP (SBP) High: >=119 mmHg (adolescents), 108 mmHg (children), 101 mmHg (in early children), 98 mmHg (infants) & IFB >=20 mmHg for all age categories.
SBP Low: <=90 mmHg (adolescents), <= 80mm Hg (children), <=70 mmHg (early children), <=70 mmHg (infants) & DFB >=20 mmHg for all age categories.
Diastolic BP (DBP) High:>=78 mmHg (adolescents), >=72 mmHg (children), >=59 mmHg (in early children), >=54 mmHg (infants) & IFB >=10 mmHg for all age categories.
DBP Low:<=54 mmHg (adolescents), <=48 mmHg (children), <=34 mmHg (early children), <=34 mmHg (infants) & DFB >=10 mmHg for all age categories.

Analysis was performed on safety population. One participant may be counted in multiple (more than 1) categories.

Posted

Count of Participants

Participants

From Baseline up to End of Study (64 weeks)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Primary

Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities

Criteria for potentially clinically significant ECG abnormalities:

High PR Interval: >=180 milliseconds (ms) in adolescents, 170 ms in children, 160 ms in early children, and 140 ms in infants;
High QRS Interval: >=110 ms in adolescents, 100 ms in children, 95 ms in early children and 85 ms in infants;
Prolonged QTc Fridericia (QTc F): >450 ms in male adolescents, children, early children and infants or 470 ms in female adolescents,
QTc F >500 ms;
QTc F increase from baseline >60 ms.

Analysis was performed on safety population.

Posted

Count of Participants

Participants

From Baseline up to End of Study (64 weeks)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Primary

Change From Baseline in Safety Biomarker Level: High Sensitivity C Reactive Protein (hsCRP) at Week 64

Analysis was performed on safety population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Posted

Mean

Standard Deviation

mg/L

Baseline, Week 64 (pre-infusion)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort	Participants aged <6 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Primary

Change From Baseline in Safety Biomarker: Ceramide Level at Week 64

Analysis was performed on safety population.

Posted

Mean

Standard Deviation

mg/L

Baseline, Week 64 (pre-infusion)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort	Participants aged <6 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Primary

Change From Baseline in Safety Biomarker: Iron at Week 64

Analysis was performed on safety population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Posted

Mean

Standard Deviation

umol/L

Baseline, Week 64 (pre-infusion)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort	Participants aged <6 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Primary

Change From Baseline in Safety Biomarker: Cardiac Troponin I and Ferritin at Week 64

Analysis was performed on safety population. Here 'number analyzed' = participants with available data for specified categories.

Posted

Mean

Standard Deviation

μg/L

Baseline, Week 64 (pre-infusion)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort	Participants aged <6 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Primary

Change From Baseline in Safety Biomarker: Interleukin (IL)-6 and IL-8 at Week 24

Analysis was performed on safety population. Here 'number analyzed'=participants with available data for specified categories. Data was not planned to be collected and reported for the Infant/Early Child Cohort, per protocol.

Posted

Mean

Standard Deviation

ng/L

Baseline, Week 24 (pre-infusion, last assessment)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Total Participants	All participants received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. The target maintenance dose was 3.0 mg/kg, which was maintained for the remaining duration of 64 treatment weeks.

Primary

Change From Baseline in Safety Biomarker: Calcitonin at Week 64

Analysis was performed on safety population.

Posted

Mean

Standard Deviation

ng/L

Baseline, Week 64 (pre-infusion)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort	Participants aged <6 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Primary

Doppler Echocardiogram: Absolute Change From Baseline in Left Ventricular Ejection Fraction at Week 52

Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Posted

Mean

Standard Deviation

percent ejection fraction

Baseline, Week 52 (last assessment)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort	Participants aged <6 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Primary

Number of Participants With Treatment-Emergent Antibody: Treatment-Induced/Treatment-Boosted Anti-drug Antibodies and Neutralizing Antibody (NAb)

Serum samples for immunogenicity assessment were analyzed to detect ADA. ADA response were categorized as: treatment emergent antibody i.e. treatment-induced/treatment-boosted response. A participant whose ADA status was positive anytime post-baseline and was negative or missing at baseline was considered to have treatment induced ADA. A participant whose ADA status was positive at baseline (pre-existing ADA) and the ADA titer level anytime post-baseline was significantly higher than that at baseline is considered to have treatment boosted ADA. Positive samples in the ADA assay were further analyzed in the NAb assay as positive NAb inhibition of catalytic activity and positive NAb inhibition of cellular uptake.

Analysis was performed on safety population.

Posted

Count of Participants

Participants

From Baseline up to Week 64

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Primary

Number of Participants With Abnormalities in Liver Ultrasound Doppler at Week 52

Evidence of portal hypertension was assessed by portal vein direction from liver ultrasound doppler.

Analysis was performed on safety population.

Posted

Count of Participants

Participants

Week 52 (last assessment)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort	Participants aged <6 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Secondary

Pharmacokinetic (PK) Parameter: Plasma Concentration of Olipudase Alfa at the End of Infusion (Ceoi)

Ceoi was defined as the plasma concentration at the end of infusion (EOI). Data collected for child and Infant/child age groups at 0-30 min from end of infusion was considered at end of infusion.

Analysis was performed on PK population which included all participants who received at least 1 infusion of study medication and had evaluable PK data.

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Mean

Standard Deviation

micrograms per milliliter (μg/mL)

At the end of infusion of the first 3.0 mg/kg dose and at Week 52

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Secondary

Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) of Olipudase Alfa

Cmax: maximum plasma concentration observed.

Analysis was performed on PK population.

Posted

Mean

Standard Deviation

μg/mL

Adolescent: at pre-infusion, EOI, 2 h, 6 h, 24 h, 48 h & 72 h (at first 3.0 mg/kg dose) or 96 h (at Week 52) post EOI; Child & infant/early child: pre-infusion, 0-30 min, 2-4 h, 6-12 h, 24-36 h, and 84-96 h post EOI at the first 3.0 mg/kg dose & Week 52

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort

Secondary

Pharmacokinetic Parameter: AUC0-last, AUC(0-tau) of Olipudase Alfa

AUClast: Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the time of last measured concentration.

AUC(0-tau): area under the plot of the drug concentration versus the time curve from time "0" to the end of the dosing interval (tau), where dosing interval was 2 weeks.

Analysis was performed on PK population.

Posted

Mean

Standard Deviation

μg*h/mL

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Secondary

Pharmacokinetic Parameter: Terminal Half-Life of Olipudase Alfa

Half-life is the time measured for the plasma concentration of drug to decrease by one half.

Analysis was performed on PK population

Posted

Mean

Standard Deviation

hours (h)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort

Secondary

Pharmacokinetic Parameter: Total Body Clearance (CL) of Olipudase Alfa

Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Total body clearance of a drug from the plasma calculated using equations below: CL = Dose / AUC after the first dose.

Analysis was performed on PK population.

Posted

Mean

Standard Deviation

milliliter/hour/kilograms (mL/h/kg)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Secondary

Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Olipudase Alfa

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

Analysis was performed on PK population.

Posted

Mean

Standard Deviation

milliliter per kilogram (mL/kg)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Secondary

Pharmacokinetic Parameter: Time to Reach Cmax (Tmax) of Olipudase Alfa

tmax: time to reach maximum plasma concentration observed.

Analysis was performed on PK population.

Posted

Median

Full Range

hours (h)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort

Secondary

Percent Change From Baseline in Spleen Volume and Liver Volume at Week 52

Spleen and liver volumes was assessed by abdominal magnetic resonance imaging (MRI).

Analysis was performed on modified intent-to-treat (mITT) population which included all participants who were exposed to IMP, regardless of the amount of treatment administered (partial or total).

Posted

Mean

Standard Deviation

percent change

Baseline, Week 52 (last assessment)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort

Secondary

Change From Baseline in Interstitial Lung Disease Score Measured Using High Resolution Computed Tomography (HRCT) at Week 52 For Both Lungs

Pulmonary imaging of chest using HRCT was obtained to quantitate the degree of possible infiltrative lung disease. Lung fields were assessed by a central reader & scored subjectively for the degree of interstitial lung disease on a scale ranges from 0 =normal, 1 =mild, 2=moderate and 3 =severe, where higher scores indicate more severity.

Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Week 52 (last assessment)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Secondary

Change From Baseline in Height Z-Scores at Week 52

Z-score for height of participants was evaluated. Height Z-Score, i.e., the height-for-age Z Score, is the number of standard deviations of the actual height of a child from the median height of the children of the corresponding age and sex as determined from the standard sample. A height Z-score of 0 is equal to the median and is considered normal. Negative numbers indicate values lower than the median and positive numbers indicate values higher than the median. For analysis, mean Z-score was calculated and an increase of mean height Z-score from baseline indicates an improvement on growth.

Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Posted

Mean

Standard Deviation

Z-score

Baseline, Week 52 (last assessment)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Secondary

Percent Change From Baseline in Percent Predicted Hemoglobin-Adjusted Diffusing Capacity of Carbon Monoxide (DLco) at Week 52

Percent predicted Hemoglobin-adjusted DLco was calculated as: 100*Adjusted DLco/Predicted DLco in unit of mL CO/min/mmHg where, adjusted DLco = Observed DLco (in mL CO/min/mmHg) divided by Hemoglobin-adjusted factor. Per planned analysis, pulmonary function testing (PFT) was to be performed only on participants >=5 years of age therefore, data for participants in "age cohort: infant/early child" were not collected.

Analysis was performed on mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure. PFT was to be performed only on participants >=5 years of age and who could perform the test, therefore, for participants in "age cohort: infant/early child" data were not collected.

Posted

Mean

Standard Deviation

percent change

Baseline, Week 52 (last assessment)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Secondary

Change From Baseline in Difference Between Actual Age and Bone Age of Participants at Week 52

Hand X-ray was performed on participant's left hand, fingers and wrist to assess bone age of participants. At each visit (Baseline and Week 52), difference between the bone age and actual age at that visit was calculated. Difference in age in months was calculated as bone age in months minus real age at time of assessment (in months) at specified time points. In this outcome measure change from baseline at Week 52 in the difference between actual age and bone age (in months) is reported.

Analysis was performed on mITT population.

Posted

Mean

Standard Deviation

months

Baseline, Week 52 (last assessment)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Secondary

Change From Baseline in Cycle Ergometry: Maximum Workload at Week 52

Cardiopulmonary status was assessed using a stationary one-wheeled cycle used as an ergometer to measure a person's work output under controlled conditions. Participants were asked to ride the cycle at increasing workload levels until they could no longer proceed. The workload at which participant stopped and cannot proceed was considered as maximum workload (in watt). As per the planned analysis, this assessment was not to be performed on participants that were <=6 years of age or <120 cm in height on day 1/week 0, therefore infant/early child cohort was not evaluable.

Analysis was performed on mITT population. Here, overall number of participants analysed = participants with available data for this outcome measure. Data not collected in participants <=6 years old, per protocol.

Posted

Mean

Standard Deviation

watts

Baseline, Week 52 (last assessment)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Secondary

Physician's Global Assessment of Participant's Progress: Observed Scores at Week 52

Physician assessed participant's current clinical status (refers to clinical status at Week 52 in comparison to Baseline) was evaluated by marking 1 of the following 7 categories: • marked improvement, • moderate improvement, • mild improvement, • no change, • mild worsening, • moderate worsening, or • marked worsening. These 7 categories were converted to scores as follows: 3 = marked improvement of daily activities, 2 = moderate improvement of daily activities, 1 = mild improvement of daily activities, 0 = no change, -1 = mild worsening of daily activities, -2 = moderate worsening of daily activities, -3 = marked worsening of daily activities where higher score indicated improvement in daily activities as compared to baseline. In this outcome measure, observed scores of participant's clinical status at Week 52 are reported.

Analysis was performed on mITT population.

Posted

Mean

Standard Deviation

score on a scale

Week 52 (last assessment)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort

Secondary

Percent Change From Baseline in Efficacy Biomarkers Level at Week 52

Efficacy biomarkers included chitotriosidase, chemokine ligand 18 (CCL18), angiotensin-converting enzyme (ACE).

Analysis was performed on mITT population. Here 'number analyzed' = participants with available data for specified category.

Posted

Mean

Standard Deviation

percent change

Baseline, Week 52

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort

Secondary

Percent Change From Baseline in Lipid Profile at Week 52

Lipid profile parameters included low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol and triglycerides.

Analysis was performed on mITT population. Here, 'number analyzed' = participants with available data for specified category.

Posted

Mean

Standard Deviation

percent change

Baseline, Week 52

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort

Secondary

Percent Change From Baseline in Bone Biomarkers at Week 52

Bone biomarkers included bone specific alkaline phosphatase, C-Telopeptide.

Analysis was performed on mITT population. Here 'number analyzed' = participants with available data for specified category.

Posted

Mean

Standard Deviation

percent change

Baseline, Week 52

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort	Participants aged <6 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.

Secondary

Change From Baseline in Health Outcome Questionnaires : Pediatric Quality of Life (PedsQL) Generic Core Total Scale Scores at Week 52

PedsQL includes a child self-report (CS-R) for participants 5 to 18 years and parents' report (PR) of participants 2 to 18 years. CS-R: 23-item PedsQL Generic Core Scales report includes 4 scales, Physical (P), Emotional (E), Social (S), and School Functioning (SF). PR: 21-item PedsQL Generic Core Scales report includes P, E, S, and SF scales. Each item used a 5-point rating scale ( from 0=never to 4=almost always). Items are reverse scored and linearly transformed to a 0 (almost always) -100 (never) scale. Higher score indicates better Health Related Quality of Life (HRQoL). P, E, S and SF summary scores are calculated as mean of respective functioning items. Psychosocial Health Summary Score is calculated as mean of 13 or 15 items (E, S and SF). Generic core total scale score is calculated as the mean of all the 21 or 23 items (P, E, S and SF). All summary/total scores are mean of specific items and they all have values ranges from 0 to 100, where higher score=better HRQoL.

Analysis performed on mITT population. Number of participants analyzed=participants with available data. PedsQL includes CS-R age 5 to18 (scoring categories 5 to 7, 8 to 12 and 13 to 18 years); PR age 2 to 18 (scoring categories 2 to 4, 5 to 7, 8 to 12 and 13 to 18 years). Since PedsQL scoring age categories are not the same as the age cohort defined for the study and since this is a single arm study, overall mITT population with available data is reported for this outcome.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Week 52 (last assessment)

ID	Title	Description
OG000	Total Participants

Secondary

Percent Change From Baseline in Pharmacodynamic Biomarkers: Plasma Sphingomyelin and Lyso-Sphingomyelin Levels at Week 52

Sphingomyelin and Lyso-sphingomyelin levels were assessed in plasma. Lyso-sphingomyelin is a metabolite of sphingomyelin.

Analysis was performed on PD population.

Posted

Mean

Standard Deviation

percent change

Baseline, Week 52 (Pre- infusion)

ID	Title	Description
OG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
OG002	Olipudase Alfa: Infant/Early Child Cohort

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Talipes	Congenital, familial and genetic disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected9 at risk EG0020 events0 affected7 at risk EG0031 events1 affected20 at risk
Anaphylactic Reaction	Immune system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected9 at risk EG0021 events1 affected7 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected9 at risk EG0022 events2 affected7 at risk EG003
Pneumonia Mycoplasmal	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected9 at risk EG0020 events0 affected7 at risk EG003
Femur Fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected9 at risk EG0020 events0 affected7 at risk EG003
Alanine Aminotransferase Increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected9 at risk EG0023 events1 affected7 at risk EG003
Respiratory Failure	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0011 events1 affected9 at risk EG0020 events0 affected7 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected9 at risk EG0021 events1 affected7 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0010 events0 affected9 at risk EG0021 events1 affected7 at risk EG003

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal Pain	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG00119 events5 affected9 at risk EG0021 events1 affected7 at risk EG00320 events6 affected20 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0005 events2 affected4 at risk EG00110 events5 affected9 at risk EG0027 events4 affected7 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0003 events2 affected4 at risk EG00121 events6 affected9 at risk EG00214 events4 affected7 at risk EG003
Pyrexia	General disorders	MedDRA 22.0	Systematic Assessment	EG0003 events1 affected4 at risk EG00124 events7 affected9 at risk EG00229 events7 affected7 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0004 events2 affected4 at risk EG00113 events5 affected9 at risk EG00211 events4 affected7 at risk EG003
Upper Respiratory Tract Infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0014 events3 affected9 at risk EG00213 events5 affected7 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG00155 events3 affected9 at risk EG00233 events3 affected7 at risk EG003
Scratch	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG00136 events2 affected9 at risk EG0028 events2 affected7 at risk EG003
Headache	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG00012 events2 affected4 at risk EG00121 events5 affected9 at risk EG0025 events1 affected7 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0003 events2 affected4 at risk EG00115 events7 affected9 at risk EG00213 events5 affected7 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0016 events3 affected9 at risk EG00211 events1 affected7 at risk EG003
Nasal Congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG0015 events3 affected9 at risk EG00213 events3 affected7 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG00113 events3 affected9 at risk EG0023 events2 affected7 at risk EG003
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected4 at risk EG00120 events2 affected9 at risk EG0023 events1 affected7 at risk EG003

ID	Term
D009542	Niemann-Pick Diseases
D013106	Sphingolipidoses
D020140	Lysosomal Storage Diseases, Nervous System
D020739	Brain Diseases, Metabolic, Inborn
D001928	Brain Diseases, Metabolic
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D015616	Histiocytosis, Non-Langerhans-Cell
D015614	Histiocytosis
D008206	Lymphatic Diseases
D006425	Hemic and Lymphatic Diseases
D008661	Metabolism, Inborn Errors
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D008064	Lipidoses
D008052	Lipid Metabolism, Inborn Errors
D016464	Lysosomal Storage Diseases
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D052439	Lipid Metabolism Disorders

ID	Title	Description
BG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to < 18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0 , 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
BG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
BG002	Olipudase Alfa: Infant/Early Child Cohort	Participants aged <6 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Olipudase Alfa: Adolescent Cohort	Participants aged 12 to <18 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.	4	0	4	4	4
EG001	Olipudase Alfa: Child Cohort	Participants aged 6 to <12 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.	9	1	9	9	9
EG002	Olipudase Alfa: Infant/Early Child Cohort	Participants aged <6 years received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. Three (3) mg/kg was the target maintenance dose, which was maintained for the remaining duration of 64 treatment weeks.	7	4	7	7	7
EG003	Total Participants	All participants received IV infusion of olipudase alfa Q2W for 64 weeks. Each participant underwent a dose escalation according to the following paradigm: 0.03, 0.1, 0.3, 0.3, 0.6, 0.6, 1.0, 2.0, 3.0 mg/kg. The target maintenance dose was 3.0 mg/kg, which was maintained for the remaining duration of 64 treatment weeks.	20	5	20	20	20