Trial Outcomes & Findings for Safety, Tolerability, PK, and Efficacy Evaluation of Repeat Ascending Doses of Olipudase Alfa in Pediatric Patients <18 Years of Age With Acid Sphingomyelinase Deficiency (NCT NCT02292654)

NCT ID: NCT02292654

Last Updated: 2022-03-23

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 20 participants
• Primary outcome timeframe: From Baseline up to End of study (64 weeks)
• Results posted on: 2022-03-23

Participant Flow

The study was conducted at 6 sites in 6 countries between 01 May 2015 and 09 December 2019.

A total of 23 participants were screened out of which 20 participants were included and treated in this study.

Participant milestones

Measure	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.	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.	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.
Overall Study STARTED	4	9	7
Overall Study COMPLETED	4	9	7
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Here, number analyzed = participants with available data for specified measure.

Baseline characteristics by cohort

Measure	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Total n=20 Participants Total of all reporting groups
Age, Continuous	14.84 years STANDARD_DEVIATION 2.22 • n=4 Participants	8.69 years STANDARD_DEVIATION 1.69 • n=9 Participants	3.77 years STANDARD_DEVIATION 1.44 • n=7 Participants	8.20 years STANDARD_DEVIATION 4.39 • n=20 Participants
Sex: Female, Male Female	1 Participants n=4 Participants	5 Participants n=9 Participants	4 Participants n=7 Participants	10 Participants n=20 Participants
Sex: Female, Male Male	3 Participants n=4 Participants	4 Participants n=9 Participants	3 Participants n=7 Participants	10 Participants n=20 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=4 Participants	0 Participants n=9 Participants	0 Participants n=7 Participants	0 Participants n=20 Participants
Race/Ethnicity, Customized Black	0 Participants n=4 Participants	0 Participants n=9 Participants	0 Participants n=7 Participants	0 Participants n=20 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=4 Participants	0 Participants n=9 Participants	0 Participants n=7 Participants	0 Participants n=20 Participants
Race/Ethnicity, Customized White	3 Participants n=4 Participants	7 Participants n=9 Participants	7 Participants n=7 Participants	17 Participants n=20 Participants
Race/Ethnicity, Customized Southeast Asian	1 Participants n=4 Participants	1 Participants n=9 Participants	0 Participants n=7 Participants	2 Participants n=20 Participants
Race/Ethnicity, Customized Northeast Asian	0 Participants n=4 Participants	0 Participants n=9 Participants	0 Participants n=7 Participants	0 Participants n=20 Participants
Race/Ethnicity, Customized Not reported	0 Participants n=4 Participants	0 Participants n=9 Participants	0 Participants n=7 Participants	0 Participants n=20 Participants
Race/Ethnicity, Customized Other	0 Participants n=4 Participants	1 Participants n=9 Participants	0 Participants n=7 Participants	1 Participants n=20 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=4 Participants	0 Participants n=9 Participants	0 Participants n=7 Participants	0 Participants n=20 Participants
High Sensitivity C Reactive Protein (hsCRP) Level in Plasma	1.863 milligrams per liter (mg/L) STANDARD_DEVIATION 1.855 • n=4 Participants • Here, number analyzed = participants with available data for specified measure.	0.410 milligrams per liter (mg/L) STANDARD_DEVIATION 0.337 • n=9 Participants • Here, number analyzed = participants with available data for specified measure.	0.306 milligrams per liter (mg/L) STANDARD_DEVIATION 0.249 • n=5 Participants • Here, number analyzed = participants with available data for specified measure.	0.704 milligrams per liter (mg/L) STANDARD_DEVIATION 1.041 • n=18 Participants • Here, number analyzed = participants with available data for specified measure.
Safety Biomarker: Ceramide Level in Plasma	7.13 mg/L STANDARD_DEVIATION 2.14 • n=4 Participants	5.57 mg/L STANDARD_DEVIATION 1.87 • n=9 Participants	8.01 mg/L STANDARD_DEVIATION 5.30 • n=7 Participants	6.74 mg/L STANDARD_DEVIATION 3.51 • n=20 Participants
Safety Biomarker: Iron Level in Plasma	10.13 micromole/liter (umol/L) STANDARD_DEVIATION 2.38 • n=4 Participants • Here, number analyzed = participants with available data for specified measure.	10.96 micromole/liter (umol/L) STANDARD_DEVIATION 2.31 • n=9 Participants • Here, number analyzed = participants with available data for specified measure.	8.52 micromole/liter (umol/L) STANDARD_DEVIATION 1.81 • n=5 Participants • Here, number analyzed = participants with available data for specified measure.	10.09 micromole/liter (umol/L) STANDARD_DEVIATION 2.32 • n=18 Participants • Here, number analyzed = participants with available data for specified measure.
Safety Biomarker: Cardiac Troponin I Level in Plasma	0.020 micrograms per liter (μg/L) STANDARD_DEVIATION 0.000 • n=4 Participants • Here, number analyzed = participants with available data for specified measure.	0.020 micrograms per liter (μg/L) STANDARD_DEVIATION 0.000 • n=9 Participants • Here, number analyzed = participants with available data for specified measure.	0.020 micrograms per liter (μg/L) STANDARD_DEVIATION 0.000 • n=5 Participants • Here, number analyzed = participants with available data for specified measure.	0.020 micrograms per liter (μg/L) STANDARD_DEVIATION 0.000 • n=18 Participants • Here, number analyzed = participants with available data for specified measure.
Safety Biomarker: Ferritin Level in Plasma	65.775 μg/L STANDARD_DEVIATION 21.088 • n=4 Participants	68.700 μg/L STANDARD_DEVIATION 36.733 • n=9 Participants	46.329 μg/L STANDARD_DEVIATION 26.500 • n=7 Participants	60.285 μg/L STANDARD_DEVIATION 31.173 • n=20 Participants
Safety Biomarker: Interleukin (IL)-6 Level in Plasma	2.27 nanogram/liter (ng/L) STANDARD_DEVIATION 0.87 • n=4 Participants • Here, number analyzed = participants with available data for specified measure. Here, number analyzed = '0' represented that data were not calculated for specified category due to non-availability of evaluable participants.	11.15 nanogram/liter (ng/L) STANDARD_DEVIATION 25.62 • n=9 Participants • Here, number analyzed = participants with available data for specified measure. Here, number analyzed = '0' represented that data were not calculated for specified category due to non-availability of evaluable participants.	—	8.73 nanogram/liter (ng/L) STANDARD_DEVIATION 21.84 • n=13 Participants • Here, number analyzed = participants with available data for specified measure. Here, number analyzed = '0' represented that data were not calculated for specified category due to non-availability of evaluable participants.
Safety Biomarker: IL-8 Level in Plasma	24.75 ng/L STANDARD_DEVIATION 14.50 • n=4 Participants • Here, number analyzed = participants with available data for specified measure. Here, number analyzed = '0' represented that data were not calculated for specified category due to non-availability of evaluable participants.	35.72 ng/L STANDARD_DEVIATION 29.15 • n=9 Participants • Here, number analyzed = participants with available data for specified measure. Here, number analyzed = '0' represented that data were not calculated for specified category due to non-availability of evaluable participants.	—	32.35 ng/L STANDARD_DEVIATION 25.43 • n=13 Participants • Here, number analyzed = participants with available data for specified measure. Here, number analyzed = '0' represented that data were not calculated for specified category due to non-availability of evaluable participants.
Safety Biomarker: Calcitonin Level in Plasma	7.675 ng/L STANDARD_DEVIATION 13.330 • n=4 Participants	9.031 ng/L STANDARD_DEVIATION 8.601 • n=9 Participants	12.991 ng/L STANDARD_DEVIATION 7.843 • n=7 Participants	10.146 ng/L STANDARD_DEVIATION 9.137 • n=20 Participants
Percent Left Ventricular Ejection Fraction	60.50 percent ejection fraction STANDARD_DEVIATION 4.04 • n=4 Participants • Here, number analyzed = participants with available data for specified measure.	64.25 percent ejection fraction STANDARD_DEVIATION 6.27 • n=8 Participants • Here, number analyzed = participants with available data for specified measure.	68.71 percent ejection fraction STANDARD_DEVIATION 7.16 • n=7 Participants • Here, number analyzed = participants with available data for specified measure.	65.11 percent ejection fraction STANDARD_DEVIATION 6.72 • n=19 Participants • Here, number analyzed = participants with available data for specified measure.
Pharmacodynamic Biomarker: Sphingomyelin in Plasma	348.3 mg/L STANDARD_DEVIATION 27.5 • n=4 Participants	430.8 mg/L STANDARD_DEVIATION 191.3 • n=9 Participants	318.7 mg/L STANDARD_DEVIATION 41.0 • n=7 Participants	375.1 mg/L STANDARD_DEVIATION 137.3 • n=20 Participants
Pharmacodynamic Biomarker: Lyso-Sphingomyelin in Plasma	488.250 ug/L STANDARD_DEVIATION 153.489 • n=4 Participants	653.667 ug/L STANDARD_DEVIATION 226.301 • n=9 Participants	670.000 ug/L STANDARD_DEVIATION 382.137 • n=7 Participants	626.300 ug/L STANDARD_DEVIATION 276.528 • n=20 Participants

PRIMARY outcome

Timeframe: From Baseline up to End of study (64 weeks)

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

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).

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any TEAEs potentially related to study drug	6 Participants	5 Participants	2 Participants	13 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any TEAEs	9 Participants	7 Participants	4 Participants	20 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any TEAEs leading to death	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any TEAEs leading to dose reduction	4 Participants	3 Participants	0 Participants	7 Participants

PRIMARY outcome

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

Population: Analysis was performed on safety population.

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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Number of Participants With Infusion-Associated Reactions (IARs)	6 Participants	5 Participants	0 Participants	11 Participants

PRIMARY outcome

Timeframe: Baseline, Week 52 (last complete assessment)

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

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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Number of Participants With Change in Physical Examination Heart	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Change in Physical Examination Skin	1 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Change in Physical Examination Extremities/Joints	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Change in Physical Examination General Appearance	1 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Change in Physical Examination Head, Eyes, Ears, Nose and Throat	0 Participants	2 Participants	2 Participants	4 Participants
Number of Participants With Change in Physical Examination Lymph Nodes	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Change in Physical Examination Lungs	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Change in Physical Examination Abdomen	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline, Week 52 (last assessment)

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

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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Number of Participants With Change in Neurological Examination Coordination Examination	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Change in Neurological Examination Cranial Nerve Examination	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Change in Neurological Examination Extrapyramidal Features	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Change in Neurological Examination Fundoscopy	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Change in Neurological Examination Gait and Coordination Examination	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Change in Neurological Examination Motor Examination, Tone	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Change in Neurological Examination Peripheral Nervous System	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Change in Neurological Examination Reflexes Examination	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Change in Neurological Examination Sensory Examination	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Change in Neurological Examination Strength Examination	0 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Change in Neurological Examination Mental Status	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: At End of Study (Week 64)

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

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

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Number of Participants With Abnormal Liver Function Laboratory Values at the End of Study Alkaline Phosphatase	2 Participants	0 Participants	2 Participants	4 Participants
Number of Participants With Abnormal Liver Function Laboratory Values at the End of Study ALT	1 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Abnormal Liver Function Laboratory Values at the End of Study AST	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Liver Function Laboratory Values at the End of Study Total Bilirubin	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From Baseline up to End of Study (64 weeks)

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

• 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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities Heart Rate High	5 Participants	3 Participants	0 Participants	8 Participants
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities Heart Rate Low	0 Participants	7 Participants	1 Participants	8 Participants
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities SBP High	6 Participants	6 Participants	3 Participants	15 Participants
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities SBP Low	5 Participants	0 Participants	2 Participants	7 Participants
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities DBP High	8 Participants	7 Participants	4 Participants	19 Participants
Number of Participants With Potentially Clinically Significant Vital Sign Abnormalities DBP Low	9 Participants	2 Participants	4 Participants	15 Participants

PRIMARY outcome

Timeframe: From Baseline up to End of Study (64 weeks)

Population: Analysis was performed on safety population.

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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities High PR Duration	2 Participants	2 Participants	2 Participants	6 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities High QRS Duration	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Prolonged QTc F	1 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QTc F >500 ms	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities QTc F increase from baseline >60 ms	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline, Week 64 (pre-infusion)

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

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=5 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=18 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.
Change From Baseline in Safety Biomarker Level: High Sensitivity C Reactive Protein (hsCRP) at Week 64	-0.168 mg/L Standard Deviation 0.411	-0.206 mg/L Standard Deviation 0.249	-1.603 mg/L Standard Deviation 1.976	-0.497 mg/L Standard Deviation 1.074

PRIMARY outcome

Timeframe: Baseline, Week 64 (pre-infusion)

Population: Analysis was performed on safety population.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Change From Baseline in Safety Biomarker: Ceramide Level at Week 64	-3.23 mg/L Standard Deviation 2.17	-5.93 mg/L Standard Deviation 4.91	-3.90 mg/L Standard Deviation 2.41	-4.31 mg/L Standard Deviation 3.48

PRIMARY outcome

Timeframe: Baseline, Week 64 (pre-infusion)

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

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=8 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=5 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=17 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.
Change From Baseline in Safety Biomarker: Iron at Week 64	-0.41 umol/L Standard Deviation 5.07	1.52 umol/L Standard Deviation 4.31	1.40 umol/L Standard Deviation 3.53	0.58 umol/L Standard Deviation 4.38

PRIMARY outcome

Timeframe: Baseline, Week 64 (pre-infusion)

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

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Change From Baseline in Safety Biomarker: Cardiac Troponin I and Ferritin at Week 64 Troponin: Pre-infusion: Week 64	0.000 μg/L Standard Deviation 0.000	0.000 μg/L Standard Deviation 0.000	0.000 μg/L Standard Deviation 0.000	0.000 μg/L Standard Deviation 0.000
Change From Baseline in Safety Biomarker: Cardiac Troponin I and Ferritin at Week 64 Ferritin: Pre-infusion: Week 64	-45.611 μg/L Standard Deviation 32.963	-28.186 μg/L Standard Deviation 19.793	-38.325 μg/L Standard Deviation 16.438	-38.055 μg/L Standard Deviation 26.207

PRIMARY outcome

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

Population: 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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=13 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	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.
Change From Baseline in Safety Biomarker: Interleukin (IL)-6 and IL-8 at Week 24 IL-6	0.89 ng/L Standard Deviation 5.66	0.77 ng/L Standard Deviation 4.95	0.47 ng/L Standard Deviation 3.23	—
Change From Baseline in Safety Biomarker: Interleukin (IL)-6 and IL-8 at Week 24 IL-8	-18.22 ng/L Standard Deviation 29.15	-14.85 ng/L Standard Deviation 25.43	-7.25 ng/L Standard Deviation 14.50	—

PRIMARY outcome

Timeframe: Baseline, Week 64 (pre-infusion)

Population: Analysis was performed on safety population.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Change From Baseline in Safety Biomarker: Calcitonin at Week 64	-5.337 ng/L Standard Deviation 3.962	-8.609 ng/L Standard Deviation 6.359	3.612 ng/L Standard Deviation 7.225	-4.710 ng/L Standard Deviation 6.929

PRIMARY outcome

Timeframe: Baseline, Week 52 (last assessment)

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

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=7 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=6 Participants 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.	Olipudase Alfa: Adolescent Cohort n=3 Participants 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.	Total Participants n=16 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.
Doppler Echocardiogram: Absolute Change From Baseline in Left Ventricular Ejection Fraction at Week 52	-1.00 percent ejection fraction Standard Deviation 5.16	1.17 percent ejection fraction Standard Deviation 4.83	0.33 percent ejection fraction Standard Deviation 4.51	0.06 percent ejection fraction Standard Deviation 4.71

PRIMARY outcome

Timeframe: From Baseline up to Week 64

Population: Analysis was performed on safety population.

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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Number of Participants With Treatment-Emergent Antibody: Treatment-Induced/Treatment-Boosted Anti-drug Antibodies and Neutralizing Antibody (NAb) ADA positive since first dose of olipudase alfa	7 Participants	3 Participants	2 Participants	12 Participants
Number of Participants With Treatment-Emergent Antibody: Treatment-Induced/Treatment-Boosted Anti-drug Antibodies and Neutralizing Antibody (NAb) Positive NAb of catalytic activity	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Treatment-Emergent Antibody: Treatment-Induced/Treatment-Boosted Anti-drug Antibodies and Neutralizing Antibody (NAb) Positive NAb of cellular uptake	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Antibody: Treatment-Induced/Treatment-Boosted Anti-drug Antibodies and Neutralizing Antibody (NAb) Treatment Induced ADA	6 Participants	3 Participants	2 Participants	11 Participants
Number of Participants With Treatment-Emergent Antibody: Treatment-Induced/Treatment-Boosted Anti-drug Antibodies and Neutralizing Antibody (NAb) Treatment boosted ADA	1 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Week 52 (last assessment)

Population: Analysis was performed on safety population.

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

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Number of Participants With Abnormalities in Liver Ultrasound Doppler at Week 52	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

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

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

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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	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.
Pharmacokinetic (PK) Parameter: Plasma Concentration of Olipudase Alfa at the End of Infusion (Ceoi) 3.0 mg/kg at First dose	23.0 micrograms per milliliter (μg/mL) Standard Deviation 3.93	22.1 micrograms per milliliter (μg/mL) Standard Deviation 7.19	28.0 micrograms per milliliter (μg/mL) Standard Deviation 4.88	—
Pharmacokinetic (PK) Parameter: Plasma Concentration of Olipudase Alfa at the End of Infusion (Ceoi) 3.0 mg/kg at Day 52	24.4 micrograms per milliliter (μg/mL) Standard Deviation 7.51	22.4 micrograms per milliliter (μg/mL) Standard Deviation 4.18	22.4 micrograms per milliliter (μg/mL) Standard Deviation 1.02	—

SECONDARY outcome

Timeframe: 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

Population: Analysis was performed on PK population.

Cmax: maximum plasma concentration observed.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	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.
Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) of Olipudase Alfa 3.0 mg/kg at First dose	23.0 μg/mL Standard Deviation 3.93	22.1 μg/mL Standard Deviation 7.19	28.0 μg/mL Standard Deviation 4.88	—
Pharmacokinetic Parameter: Maximum Observed Plasma Concentration (Cmax) of Olipudase Alfa 3.0 mg/kg at Week 52	24.4 μg/mL Standard Deviation 7.51	22.4 μg/mL Standard Deviation 4.18	22.4 μg/mL Standard Deviation 1.02	—

SECONDARY outcome

Timeframe: 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

Population: Analysis was performed on PK population.

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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	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.
Pharmacokinetic Parameter: AUC0-last, AUC(0-tau) of Olipudase Alfa AUClast: at 3.0 mg/kg First dose	441 μg*h/mL Standard Deviation 97.8	412 μg*h/mL Standard Deviation 87.4	452 μg*h/mL Standard Deviation 49.7	—
Pharmacokinetic Parameter: AUC0-last, AUC(0-tau) of Olipudase Alfa AUClast: at 3.0 mg/kg at Week 52	482 μg*h/mL Standard Deviation 101	429 μg*h/mL Standard Deviation 62.6	461 μg*h/mL Standard Deviation 28.1	—
Pharmacokinetic Parameter: AUC0-last, AUC(0-tau) of Olipudase Alfa AUC(0-τ): at 3.0 mg/kg First dose	465 μg*h/mL Standard Deviation 102	432 μg*h/mL Standard Deviation 93.0	478 μg*h/mL Standard Deviation 55.4	—
Pharmacokinetic Parameter: AUC0-last, AUC(0-tau) of Olipudase Alfa AUC(0-τ): at 3.0 mg/kg at Week 52	508 μg*h/mL Standard Deviation 108	451 μg*h/mL Standard Deviation 68.2	489 μg*h/mL Standard Deviation 32.7	—

SECONDARY outcome

Timeframe: 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

Population: Analysis was performed on PK population

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

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	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.
Pharmacokinetic Parameter: Terminal Half-Life of Olipudase Alfa 3.0 mg/kg at Week 52	23.3 hours (h) Standard Deviation 1.42	23.6 hours (h) Standard Deviation 1.35	24.3 hours (h) Standard Deviation 2.88	—
Pharmacokinetic Parameter: Terminal Half-Life of Olipudase Alfa 3.0 mg/kg at First dose	23.1 hours (h) Standard Deviation 2.11	22.6 hours (h) Standard Deviation 1.25	17.1 hours (h) Standard Deviation 1.15	—

SECONDARY outcome

Timeframe: 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

Population: Analysis was performed on PK population.

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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	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.
Pharmacokinetic Parameter: Total Body Clearance (CL) of Olipudase Alfa 3.0 mg/kg at First dose	6.75 milliliter/hour/kilograms (mL/h/kg) Standard Deviation 1.57	7.20 milliliter/hour/kilograms (mL/h/kg) Standard Deviation 1.40	6.34 milliliter/hour/kilograms (mL/h/kg) Standard Deviation 0.741	—
Pharmacokinetic Parameter: Total Body Clearance (CL) of Olipudase Alfa 3.0 mg/kg at Week 52	6.16 milliliter/hour/kilograms (mL/h/kg) Standard Deviation 1.38	6.79 milliliter/hour/kilograms (mL/h/kg) Standard Deviation 1.08	6.16 milliliter/hour/kilograms (mL/h/kg) Standard Deviation 0.411	—

SECONDARY outcome

Timeframe: 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

Population: Analysis was performed on PK population.

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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	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.
Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Olipudase Alfa 3.0 mg/kg at First dose	166 milliliter per kilogram (mL/kg) Standard Deviation 39.1	165 milliliter per kilogram (mL/kg) Standard Deviation 31.0	133 milliliter per kilogram (mL/kg) Standard Deviation 13.5	—
Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Olipudase Alfa 3.0 mg/kg at Week 52	153 milliliter per kilogram (mL/kg) Standard Deviation 32.7	161 milliliter per kilogram (mL/kg) Standard Deviation 20.9	172 milliliter per kilogram (mL/kg) Standard Deviation 11.6	—

SECONDARY outcome

Timeframe: 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

Population: Analysis was performed on PK population.

tmax: time to reach maximum plasma concentration observed.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	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.
Pharmacokinetic Parameter: Time to Reach Cmax (Tmax) of Olipudase Alfa 3.0 mg/kg at First dose	4.00 hours (h) Interval 3.83 to 7.07	4.13 hours (h) Interval 3.75 to 8.7	3.94 hours (h) Interval 3.87 to 4.08	—
Pharmacokinetic Parameter: Time to Reach Cmax (Tmax) of Olipudase Alfa 3.0 mg/kg at Week 52	4.25 hours (h) Interval 3.75 to 9.78	4.42 hours (h) Interval 4.08 to 5.87	3.81 hours (h) Interval 3.67 to 4.03	—

SECONDARY outcome

Timeframe: Baseline, Week 52 (last assessment)

Population: 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).

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

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Percent Change From Baseline in Spleen Volume and Liver Volume at Week 52 Change in spleen volume	-46.038 percent change Standard Deviation 11.767	-54.590 percent change Standard Deviation 7.562	-46.936 percent change Standard Deviation 3.041	-49.211 percent change Standard Deviation 9.713
Percent Change From Baseline in Spleen Volume and Liver Volume at Week 52 Change in liver volume	-36.741 percent change Standard Deviation 10.469	-45.060 percent change Standard Deviation 8.203	-41.726 percent change Standard Deviation 6.130	-40.560 percent change Standard Deviation 9.370

SECONDARY outcome

Timeframe: Baseline, Week 52 (last assessment)

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

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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=6 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=19 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.
Change From Baseline in Interstitial Lung Disease Score Measured Using High Resolution Computed Tomography (HRCT) at Week 52 For Both Lungs	-0.5833 score on a scale Standard Deviation 0.7906	-0.8958 score on a scale Standard Deviation 0.9982	-0.2188 score on a scale Standard Deviation 1.0020	-0.6053 score on a scale Standard Deviation 0.8851

SECONDARY outcome

Timeframe: Baseline, Week 52 (last assessment)

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

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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=8 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=19 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.
Change From Baseline in Height Z-Scores at Week 52	0.371 Z-score Standard Deviation 0.344	0.736 Z-score Standard Deviation 0.423	0.606 Z-score Standard Deviation 0.290	0.555 Z-score Standard Deviation 0.385

SECONDARY outcome

Timeframe: Baseline, Week 52 (last assessment)

Population: 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.

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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=6 Participants 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.	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.	Olipudase Alfa: Adolescent Cohort n=3 Participants 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.	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.
Percent Change From Baseline in Percent Predicted Hemoglobin-Adjusted Diffusing Capacity of Carbon Monoxide (DLco) at Week 52	35.41 percent change Standard Deviation 35.08	—	28.01 percent change Standard Deviation 16.22	—

SECONDARY outcome

Timeframe: Baseline, Week 52 (last assessment)

Population: Analysis was performed on mITT population.

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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Change From Baseline in Difference Between Actual Age and Bone Age of Participants at Week 52	2.876 months Standard Deviation 14.048	-0.702 months Standard Deviation 9.573	1.595 months Standard Deviation 3.114	1.368 months Standard Deviation 10.781

SECONDARY outcome

Timeframe: Baseline, Week 52 (last assessment)

Population: 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.

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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=2 Participants 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.	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.	Olipudase Alfa: Adolescent Cohort n=3 Participants 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.	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.
Change From Baseline in Cycle Ergometry: Maximum Workload at Week 52	20.5 watts Standard Deviation 7.8	—	38.3 watts Standard Deviation 10.7	—

SECONDARY outcome

Timeframe: Week 52 (last assessment)

Population: Analysis was performed on mITT population.

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.

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Physician's Global Assessment of Participant's Progress: Observed Scores at Week 52	2.4 score on a scale Standard Deviation 1.0	2.7 score on a scale Standard Deviation 0.8	1.3 score on a scale Standard Deviation 1.5	2.3 score on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: Baseline, Week 52

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

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

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Percent Change From Baseline in Efficacy Biomarkers Level at Week 52 ACE at Week 52	-24.57 percent change Standard Deviation 14.15	-29.64 percent change Standard Deviation 17.80	-29.92 percent change Standard Deviation 19.59	-27.41 percent change Standard Deviation 15.87
Percent Change From Baseline in Efficacy Biomarkers Level at Week 52 Chitotriosidase at Week 52	-44.7 percent change Standard Deviation 25.0	-74.6 percent change Standard Deviation 18.1	-55.8 percent change Standard Deviation 21.1	-58.0 percent change Standard Deviation 24.8
Percent Change From Baseline in Efficacy Biomarkers Level at Week 52 CCL18 at Week 52	-66.20 percent change Standard Deviation 22.97	-68.13 percent change Standard Deviation 16.63	-55.25 percent change Standard Deviation 13.23	-64.68 percent change Standard Deviation 19.01

SECONDARY outcome

Timeframe: Baseline, Week 52

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

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

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Percent Change From Baseline in Lipid Profile at Week 52 Triglycerides at Week 52	-47.45 percent change Standard Deviation 18.08	-56.44 percent change Standard Deviation 25.01	-56.28 percent change Standard Deviation 5.95	-52.37 percent change Standard Deviation 19.02
Percent Change From Baseline in Lipid Profile at Week 52 LDL Cholesterol at Week 52	-35.82 percent change Standard Deviation 23.00	-34.04 percent change Standard Deviation 16.69	-38.31 percent change Standard Deviation 7.44	-35.78 percent change Standard Deviation 18.00
Percent Change From Baseline in Lipid Profile at Week 52 HDL Cholesterol at Week 52	87.49 percent change Standard Deviation 52.89	124.74 percent change Standard Deviation 84.57	118.63 percent change Standard Deviation 66.75	106.76 percent change Standard Deviation 66.82

SECONDARY outcome

Timeframe: Baseline, Week 52

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

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

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Percent Change From Baseline in Bone Biomarkers at Week 52 C-Telopeptide: Week 52	92.5 percent change Standard Deviation 78.4	50.6 percent change Standard Deviation 37.0	69.0 percent change Standard Deviation 93.7	74.7 percent change Standard Deviation 70.9
Percent Change From Baseline in Bone Biomarkers at Week 52 Alkaline phosphatase: Week 52	44.768 percent change Standard Deviation 50.111	35.040 percent change Standard Deviation 61.983	-9.154 percent change Standard Deviation 50.568	32.391 percent change Standard Deviation 54.292

SECONDARY outcome

Timeframe: Baseline, Week 52 (last assessment)

Population: 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.

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.

Outcome measures

Measure	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.	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.	Olipudase Alfa: Adolescent Cohort n=19 Participants 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.	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.
Change From Baseline in Health Outcome Questionnaires : Pediatric Quality of Life (PedsQL) Generic Core Total Scale Scores at Week 52 Physical Functioning Scale: Child Report	—	—	9.4 score on a scale Standard Deviation 7.9	—
Change From Baseline in Health Outcome Questionnaires : Pediatric Quality of Life (PedsQL) Generic Core Total Scale Scores at Week 52 Emotional Functioning Scale: Child Report	—	—	14.6 score on a scale Standard Deviation 15.1	—
Change From Baseline in Health Outcome Questionnaires : Pediatric Quality of Life (PedsQL) Generic Core Total Scale Scores at Week 52 Social Functioning Scale: Child Report	—	—	4.2 score on a scale Standard Deviation 13.2	—
Change From Baseline in Health Outcome Questionnaires : Pediatric Quality of Life (PedsQL) Generic Core Total Scale Scores at Week 52 School Functioning Scale: Child Report	—	—	2.1 score on a scale Standard Deviation 12.6	—
Change From Baseline in Health Outcome Questionnaires : Pediatric Quality of Life (PedsQL) Generic Core Total Scale Scores at Week 52 Psychosocial Health Summary Score: Child Report	—	—	6.8 score on a scale Standard Deviation 8.3	—
Change From Baseline in Health Outcome Questionnaires : Pediatric Quality of Life (PedsQL) Generic Core Total Scale Scores at Week 52 Generic Core Total Scale Score : Child Report	—	—	7.6 score on a scale Standard Deviation 5.5	—
Change From Baseline in Health Outcome Questionnaires : Pediatric Quality of Life (PedsQL) Generic Core Total Scale Scores at Week 52 Physical Functioning Scale: Parent Report	—	—	15.5 score on a scale Standard Deviation 15.3	—
Change From Baseline in Health Outcome Questionnaires : Pediatric Quality of Life (PedsQL) Generic Core Total Scale Scores at Week 52 Emotional Functioning Scale: Parent Report	—	—	12.2 score on a scale Standard Deviation 22.9	—
Change From Baseline in Health Outcome Questionnaires : Pediatric Quality of Life (PedsQL) Generic Core Total Scale Scores at Week 52 Social Functioning Scale:Parent Report	—	—	11.7 score on a scale Standard Deviation 19.8	—
Change From Baseline in Health Outcome Questionnaires : Pediatric Quality of Life (PedsQL) Generic Core Total Scale Scores at Week 52 School Functioning Scale: Parent Report	—	—	1.0 score on a scale Standard Deviation 20.5	—
Change From Baseline in Health Outcome Questionnaires : Pediatric Quality of Life (PedsQL) Generic Core Total Scale Scores at Week 52 Psychosocial Health Summary Score:Parent Report	—	—	8.2 score on a scale Standard Deviation 14.5	—
Change From Baseline in Health Outcome Questionnaires : Pediatric Quality of Life (PedsQL) Generic Core Total Scale Scores at Week 52 Generic Core Total Scale Score: Parent Report	—	—	10.8 score on a scale Standard Deviation 13.4	—

SECONDARY outcome

Timeframe: Baseline, Week 52 (Pre- infusion)

Population: Analysis was performed on PD population.

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

Outcome measures

Measure	Olipudase Alfa: Child Cohort n=9 Participants 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 Participants 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.	Olipudase Alfa: Adolescent Cohort n=4 Participants 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.	Total Participants n=20 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.
Percent Change From Baseline in Pharmacodynamic Biomarkers: Plasma Sphingomyelin and Lyso-Sphingomyelin Levels at Week 52 Sphingomyelin: Pre-infusion at Week 52	-37.1 percent change Standard Deviation 24.2	-18.6 percent change Standard Deviation 40.3	-4.4 percent change Standard Deviation 24.6	-24.1 percent change Standard Deviation 32.0
Percent Change From Baseline in Pharmacodynamic Biomarkers: Plasma Sphingomyelin and Lyso-Sphingomyelin Levels at Week 52 Lyso-Sphingomyelin: Pre-infusion at Week 52	-88.029 percent change Standard Deviation 8.156	-87.951 percent change Standard Deviation 1.775	-84.050 percent change Standard Deviation 5.249	-87.206 percent change Standard Deviation 5.998

Adverse Events

Olipudase Alfa: Adolescent Cohort

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Olipudase Alfa: Child Cohort

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Olipudase Alfa: Infant/Early Child Cohort

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

Total Participants

Serious events: 5 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	Olipudase Alfa: Adolescent Cohort n=4 participants at risk 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.	Olipudase Alfa: Child Cohort n=9 participants at risk 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 participants at risk 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.	Total Participants n=20 participants at risk 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.
Congenital, familial and genetic disorders Talipes	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	11.1% 1/9 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	0.00% 0/7 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	5.0% 1/20 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Immune system disorders Anaphylactic Reaction	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	0.00% 0/9 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	14.3% 1/7 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	5.0% 1/20 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Infections and infestations Gastroenteritis	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	0.00% 0/9 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	28.6% 2/7 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	10.0% 2/20 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Infections and infestations Pneumonia Mycoplasmal	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	11.1% 1/9 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	0.00% 0/7 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	5.0% 1/20 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Injury, poisoning and procedural complications Femur Fracture	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	11.1% 1/9 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	0.00% 0/7 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	5.0% 1/20 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Investigations Alanine Aminotransferase Increased	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	0.00% 0/9 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	14.3% 1/7 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	5.0% 1/20 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	11.1% 1/9 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	0.00% 0/7 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	5.0% 1/20 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Rash	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	0.00% 0/9 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	14.3% 1/7 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	5.0% 1/20 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	0.00% 0/9 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	14.3% 1/7 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	5.0% 1/20 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.

Other adverse events

Measure	Olipudase Alfa: Adolescent Cohort n=4 participants at risk 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.	Olipudase Alfa: Child Cohort n=9 participants at risk 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.	Olipudase Alfa: Infant/Early Child Cohort n=7 participants at risk 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.	Total Participants n=20 participants at risk 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.
Gastrointestinal disorders Abdominal Pain	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	55.6% 5/9 • Number of events 19 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	14.3% 1/7 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	30.0% 6/20 • Number of events 20 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Gastrointestinal disorders Diarrhoea	50.0% 2/4 • Number of events 5 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	55.6% 5/9 • Number of events 10 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	57.1% 4/7 • Number of events 7 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	55.0% 11/20 • Number of events 22 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Gastrointestinal disorders Vomiting	50.0% 2/4 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	66.7% 6/9 • Number of events 21 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	57.1% 4/7 • Number of events 14 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	60.0% 12/20 • Number of events 38 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
General disorders Pyrexia	25.0% 1/4 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	77.8% 7/9 • Number of events 24 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	100.0% 7/7 • Number of events 29 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	75.0% 15/20 • Number of events 56 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Infections and infestations Nasopharyngitis	50.0% 2/4 • Number of events 4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	55.6% 5/9 • Number of events 13 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	57.1% 4/7 • Number of events 11 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	55.0% 11/20 • Number of events 28 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	33.3% 3/9 • Number of events 4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	71.4% 5/7 • Number of events 13 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	40.0% 8/20 • Number of events 17 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Injury, poisoning and procedural complications Contusion	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	33.3% 3/9 • Number of events 55 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	42.9% 3/7 • Number of events 33 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	30.0% 6/20 • Number of events 88 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Injury, poisoning and procedural complications Scratch	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	22.2% 2/9 • Number of events 36 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	28.6% 2/7 • Number of events 8 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	20.0% 4/20 • Number of events 44 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Nervous system disorders Headache	50.0% 2/4 • Number of events 12 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	55.6% 5/9 • Number of events 21 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	14.3% 1/7 • Number of events 5 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	40.0% 8/20 • Number of events 38 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Cough	50.0% 2/4 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	77.8% 7/9 • Number of events 15 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	71.4% 5/7 • Number of events 13 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	70.0% 14/20 • Number of events 31 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	33.3% 3/9 • Number of events 6 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	14.3% 1/7 • Number of events 11 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	20.0% 4/20 • Number of events 17 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	33.3% 3/9 • Number of events 5 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	42.9% 3/7 • Number of events 13 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	30.0% 6/20 • Number of events 18 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Rash	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	33.3% 3/9 • Number of events 13 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	28.6% 2/7 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	25.0% 5/20 • Number of events 16 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/4 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	22.2% 2/9 • Number of events 20 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	14.3% 1/7 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.	15.0% 3/20 • Number of events 23 • All Adverse Events (AEs) were collected from first IMP administration up to 64 weeks regardless of seriousness or relationship to investigational product. Reported AEs are treatment-emergent adverse events that is AEs that developed/worsened during the 'on-treatment period' (time from the start of first infusion until 64 weeks). The other Non-serious adverse events section contains Events \>=2% and participants \>=2. Analysis was performed on safety population.

Additional Information

Trial Transparency Team

Sanofi

Phone: 800-633-1610

Email: Contact-US@sanofi.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
• Publication restrictions are in place

Restriction type: OTHER