Trial Outcomes & Findings for Immune Tolerance Induction Study (NCT NCT00701701)

NCT ID: NCT00701701

Last Updated: 2022-04-07

Results Overview

An Adverse event (AE) was defined as any undesirable physical, psychological, or behavioral effect experienced by participant during his/her participation in an investigational study, in conjunction with the use of the drug or biologic, whether or not product-related. TEAEs were defined as AEs that occurred or worsened during the on-treatment period (time from the start of investigational medicinal product \[IMP\] administration up to 18 months). Serious AE (SAE) was any AE that resulted in any of the following outcomes: death, was life-threatening, required or prolonged inpatient hospitalization, persistent or significant disability/incapacity; congenital anomaly; or important medical events that may jeopardize the patient or participant and may require medical or surgical intervention to prevent one of the outcomes listed above; and/or new invasive ventilator use.

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 4 participants
• Primary outcome timeframe: From Baseline up to 18 months
• Results posted on: 2022-04-07

Participant Flow

The study was conducted in 2 countries. A total of 5 participants were screened between 14 December 2008 and 17 August 2010 (dates when first participant and last participant signed informed consent), of which one participant died before enrollment.

A total of 4 participants were included and treated in this study. Participants were assigned to either Regimen A or Regimen B.

Participant milestones

Measure	Regimen A: Alglucosidase Alfa and Cyclophosphamide Participants exhibiting clinical decline since starting alglucosidase alfa (Myozyme®) therapy and having inhibitory antibodies and/or a sustained high recombinant human acid alpha-glucosidase (rhGAA) antibody titer (defined as at least 2 titers greater than or equal to \[\>=\] 25,600 obtained at least 1 month apart), regardless of their cross-reacting immunologic material (CRIM) status, were assigned to Regimen A. In Regimen A, participants received alglucosidase alfa (Myozyme®) Intravenous (IV) infusion of 20 milligram per kilogram (mg/kg) every other week (qow) for a minimum of 18 months or, until the participant reached the age of 2 years (if the participant was less than \[\<6\] months of age at the time of enrollment). In addition, cyclophosphamide 250 milligram per square meter (mg/m\^2) IV infusion was administered every 4 weeks (q4w) after Myozyme® infusion for 6 months.	Regimen B: Alglucosidase Alfa, Rituximab and Methotrexate CRIM-negative participants were assigned to Regimen B if they either(1)exhibited clinical decline since starting alglucosidase alfa (Myozyme®)therapy and did not have inhibitory antibodies and/or a sustained rhGAA antibody titer(defined as at least 2 titers \>=25,600 obtained at least 1 month apart),or(2) did not exhibit clinical decline since starting alglucosidase alfa(Myozyme®) therapy, regardless of their anti-rhGAA or inhibitory antibody status. Regimen B participants with CRIM-negative status received alglucosidase alfa(Myozyme®) IV infusion of 20 mg/kg qow for a minimum of 18 months or,until participant reached the age of 2 years (if participant was \<6 months of age at time of enrollment). In addition,rituximab 375 mg/m\^2 IV was administered weekly beginning the day after Myozyme® infusion for 4 weeks(an optional 2nd cycle could be administered at the discretion of the investigator) and biweekly methotrexate 15 mg/m\^2 subcutaneous on the day after Myozyme® infusion for 6 months.
Overall Study STARTED	1	3
Overall Study COMPLETED	1	1
Overall Study NOT COMPLETED	0	2

Reasons for withdrawal

Measure	Regimen A: Alglucosidase Alfa and Cyclophosphamide Participants exhibiting clinical decline since starting alglucosidase alfa (Myozyme®) therapy and having inhibitory antibodies and/or a sustained high recombinant human acid alpha-glucosidase (rhGAA) antibody titer (defined as at least 2 titers greater than or equal to \[\>=\] 25,600 obtained at least 1 month apart), regardless of their cross-reacting immunologic material (CRIM) status, were assigned to Regimen A. In Regimen A, participants received alglucosidase alfa (Myozyme®) Intravenous (IV) infusion of 20 milligram per kilogram (mg/kg) every other week (qow) for a minimum of 18 months or, until the participant reached the age of 2 years (if the participant was less than \[\<6\] months of age at the time of enrollment). In addition, cyclophosphamide 250 milligram per square meter (mg/m\^2) IV infusion was administered every 4 weeks (q4w) after Myozyme® infusion for 6 months.	Regimen B: Alglucosidase Alfa, Rituximab and Methotrexate CRIM-negative participants were assigned to Regimen B if they either(1)exhibited clinical decline since starting alglucosidase alfa (Myozyme®)therapy and did not have inhibitory antibodies and/or a sustained rhGAA antibody titer(defined as at least 2 titers \>=25,600 obtained at least 1 month apart),or(2) did not exhibit clinical decline since starting alglucosidase alfa(Myozyme®) therapy, regardless of their anti-rhGAA or inhibitory antibody status. Regimen B participants with CRIM-negative status received alglucosidase alfa(Myozyme®) IV infusion of 20 mg/kg qow for a minimum of 18 months or,until participant reached the age of 2 years (if participant was \<6 months of age at time of enrollment). In addition,rituximab 375 mg/m\^2 IV was administered weekly beginning the day after Myozyme® infusion for 4 weeks(an optional 2nd cycle could be administered at the discretion of the investigator) and biweekly methotrexate 15 mg/m\^2 subcutaneous on the day after Myozyme® infusion for 6 months.
Overall Study Withdrawal by Subject	0	1
Overall Study Adverse Event	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Regimen A: Alglucosidase Alfa and Cyclophosphamide n=1 Participants Participants exhibiting clinical decline since starting alglucosidase alfa (Myozyme®) therapy and having inhibitory antibodies and/or a sustained high rhGAA antibody titer (defined as at least 2 titers \>=25,600 obtained at least 1 month apart), regardless of their CRIM status, were assigned to Regimen A. In Regimen A, participants received alglucosidase alfa (Myozyme®) IV infusion of 20 mg/kg qow for a minimum of 18 months or, until the participant reached the age of 2 years (if the participant was \<6 months of age at the time of enrollment). In addition, cyclophosphamide 250 mg/m\^2 IV infusion was administered q4w after Myozyme® infusion for 6 months.	Regimen B: Alglucosidase Alfa, Rituximab and Methotrexate n=3 Participants CRIM-negative participants were assigned to Regimen B if they either(1)exhibited clinical decline since starting alglucosidase alfa (Myozyme®)therapy and did not have inhibitory antibodies and/or a sustained rhGAA antibody titer(defined as at least 2 titers \>=25,600 obtained at least 1 month apart),or(2) did not exhibit clinical decline since starting alglucosidase alfa(Myozyme®) therapy, regardless of their anti-rhGAA or inhibitory antibody status. Regimen B participants with CRIM-negative status received alglucosidase alfa(Myozyme®) IV infusion of 20 mg/kg qow for a minimum of 18 months or,until participant reached the age of 2 years (if participant was \<6 months of age at time of enrollment). In addition,rituximab 375 mg/m\^2 IV was administered weekly beginning the day after Myozyme® infusion for 4 weeks(an optional 2nd cycle could be administered at the discretion of the investigator) and biweekly methotrexate 15 mg/m\^2 subcutaneous on the day after Myozyme® infusion for 6 months.	Total n=4 Participants Total of all reporting groups
Age, Customized Infants and toddlers (28 days-23 months)	0 Participants n=1 Participants	2 Participants n=3 Participants	2 Participants n=4 Participants
Age, Customized Children (2-11 years)	1 Participants n=1 Participants	1 Participants n=3 Participants	2 Participants n=4 Participants
Sex: Female, Male Female	0 Participants n=1 Participants	2 Participants n=3 Participants	2 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=1 Participants	1 Participants n=3 Participants	2 Participants n=4 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: From Baseline up to 18 months

Population: Analysis was performed on safety set population that included participants who received at least 1 dose of alglucosidase alfa in the study.

An Adverse event (AE) was defined as any undesirable physical, psychological, or behavioral effect experienced by participant during his/her participation in an investigational study, in conjunction with the use of the drug or biologic, whether or not product-related. TEAEs were defined as AEs that occurred or worsened during the on-treatment period (time from the start of investigational medicinal product [IMP] administration up to 18 months). Serious AE (SAE) was any AE that resulted in any of the following outcomes: death, was life-threatening, required or prolonged inpatient hospitalization, persistent or significant disability/incapacity; congenital anomaly; or important medical events that may jeopardize the patient or participant and may require medical or surgical intervention to prevent one of the outcomes listed above; and/or new invasive ventilator use.

Outcome measures

Measure	Regimen A: Alglucosidase Alfa and Cyclophosphamide n=1 Participants Participants exhibiting clinical decline since starting alglucosidase alfa (Myozyme®) therapy and having inhibitory antibodies and/or a sustained high rhGAA antibody titer (defined as at least 2 titers \>=25,600 obtained at least 1 month apart), regardless of their CRIM status, were assigned to Regimen A. In Regimen A, participants received alglucosidase alfa (Myozyme®) IV infusion of 20 mg/kg qow for a minimum of 18 months or, until the participant reached the age of 2 years (if the participant was \<6 months of age at the time of enrollment). In addition, cyclophosphamide 250 mg/m\^2 IV infusion was administered q4w after Myozyme® infusion for 6 months.	Regimen B: Alglucosidase Alfa, Rituximab and Methotrexate n=3 Participants CRIM-negative participants were assigned to Regimen B if they either(1)exhibited clinical decline since starting alglucosidase alfa (Myozyme®)therapy and did not have inhibitory antibodies and/or a sustained rhGAA antibody titer(defined as at least 2 titers \>=25,600 obtained at least 1 month apart),or(2) did not exhibit clinical decline since starting alglucosidase alfa(Myozyme®) therapy, regardless of their anti-rhGAA or inhibitory antibody status. Regimen B participants with CRIM-negative status received alglucosidase alfa(Myozyme®) IV infusion of 20 mg/kg qow for a minimum of 18 months or,until participant reached the age of 2 years (if participant was \<6 months of age at time of enrollment). In addition,rituximab 375 mg/m\^2 IV was administered weekly beginning the day after Myozyme® infusion for 4 weeks(an optional 2nd cycle could be administered at the discretion of the investigator) and biweekly methotrexate 15 mg/m\^2 subcutaneous on the day after Myozyme® infusion for 6 months.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any TEAE	1 Participants	3 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any TEAE leading to withdrawal from study	0 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any Treatment-emergent SAE	1 Participants	3 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Any TEAE leading to death	0 Participants	1 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Month 18

Population: Data were not summarized for this exploratory outcome measure due to low number of enrollment of participants.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Month 18

Population: Data were not summarized for this exploratory outcome measure due to low number of enrollment of participants.

Participants with positive anti-rhGAA IgG antibody were planned to be assessed for the presence of inhibitory antibodies (inhibition of enzyme activity and inhibition of enzyme uptake). Enzyme-linked immunosorbent assay (ELISA) was used to measure inhibition of rhGAA enzymatic activity in vitro and a cell-based assay was used to measure the inhibition of the uptake of rhGAA in normal fibroblast cells by flow cytometry.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From randomization until death or study cut-off whichever comes earlier (up to 18 months)

Population: Data were not summarized for this exploratory outcome measure due to low number of enrollment of participants.

OS was defined as the time interval from the date of first IMP administration to the date of death due to any cause.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to 18 months

Population: Data were not summarized for this exploratory outcome measure due to low number of enrollment of participants.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to 18 months

Population: Data were not summarized for this exploratory outcome measure due to low number of enrollment of participants.

LVM Z-score and LVM index were assessed by echocardiograms (ECHOs). LVM Z-Score is an indicator of degree of standard deviations from the mean in a normal distribution. The normal range for LVM Z-Score is -2 to 2. Values <-2 or >2 indicate abnormal LVM Z-Score. Values less than 0 (negative values) indicate a smaller LVM than mean and values higher than 0 indicate a larger LVM than the mean. LVM index is an index value derived by normalizing LVM by body surface area. LVM index provides evidence of cardiomyopathy. LVM index values <65 gram per square meter (g/m^2) were considered as normal and LVM index values >=65 g/m^2 were considered as abnormal.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to 18 months

Population: Data were not summarized for this exploratory outcome measure due to low number of enrollment of participants.

GMFM-88 is an 88-item measure to detect gross motor function. It consists of 5 categories: lying and rolling; sitting; crawling and kneeling; standing; and walking, running and jumping. Each item is scored on a 4-point Likert scale (0=cannot do; 1=initiates [<10 percent (%) of the task]; 2=partially completes [10% to <100% of the task]; 3=task completion). The score for each dimension is expressed as a percentage of the maximum score for that dimension. Total score is obtained by adding the percentage scores for each dimension and dividing the sum by the total number of dimensions. Total score ranges from 0% to 100%, where higher scores indicate better motor functions. A total score of <7.5% demonstrates gross motor disability.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to 18 months

Population: Data were not summarized for this exploratory outcome measure due to low number of enrollment of participants.

AIMS is a 58-item reliable and valid measure of motor development for infants at risk for motor delay. It assesses infant movement in 4 positions (subscales): prone (reciprocal crawling); supine (moving hands to feet); sitting (sitting with arm support); and standing (pulls to stand). For each subscale, items are scored as "observed" or "not observed". Items in observed range create a motor window. When scoring, subscale scores are calculated by giving child credit (1 point) for observed items within motor window in addition to being given credit (1 point) for all of the less mature items before motor window. AIMS total score is calculated by summing scores for 58 items and ranges from 0-58, with lower score indicating less mature motor development and higher score indicating more mature motor development.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to 18 months

Population: Data were not summarized for this exploratory outcome measure due to low number of enrollment of participants.

Pompe PEDI is a disease specific version of PEDI which assesses functional capabilities and performance in children with Pompe disease from 2 months through adolescence.It consists of all items of original PEDI (197 functional skill items in 3 domains: self-care; mobility; and social function) and additional items in functional skills, mobility, and self-care domains to reflect clinically relevant functional skills. Each domain consists of 2 subdomains: functional skill performance and caregiver assistance scale. Norm-based scoring was developed for these additional items, and scoring algorithms for PEDI have been adjusted to reflect additional normative data collected for Pompe PEDI. Total score range for each domain (mean of subdomains) and subdomains ranges from 0-100, higher score indicates higher capability.

Outcome measures

Outcome data not reported

Adverse Events

Regimen A: Alglucosidase Alfa and Cyclophosphamide

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Regimen B: Alglucosidase Alfa, Rituximab and Methotrexate

Serious events: 3 serious events

Other events: 3 other events

Deaths: 1 deaths

Serious adverse events

Measure	Regimen A: Alglucosidase Alfa and Cyclophosphamide n=1 participants at risk Participants exhibiting clinical decline since starting alglucosidase alfa (Myozyme®) therapy and having inhibitory antibodies and/or a sustained high rhGAA antibody titer (defined as at least 2 titers \>=25,600 obtained at least 1 month apart), regardless of their CRIM status, were assigned to Regimen A. In Regimen A, participants received alglucosidase alfa (Myozyme®) IV infusion of 20 mg/kg qow for a minimum of 18 months or, until the participant reached the age of 2 years (if the participant was \<6 months of age at the time of enrollment). In addition, cyclophosphamide 250 mg/m\^2 IV infusion was administered q4w after Myozyme® infusion for 6 months.	Regimen B: Alglucosidase Alfa, Rituximab and Methotrexate n=3 participants at risk CRIM-negative participants were assigned to Regimen B if they either(1)exhibited clinical decline since starting alglucosidase alfa (Myozyme®)therapy and did not have inhibitory antibodies and/or a sustained rhGAA antibody titer(defined as at least 2 titers \>=25,600 obtained at least 1 month apart),or(2) did not exhibit clinical decline since starting alglucosidase alfa(Myozyme®) therapy, regardless of their anti-rhGAA or inhibitory antibody status. Regimen B participants with CRIM-negative status received alglucosidase alfa(Myozyme®) IV infusion of 20 mg/kg qow for a minimum of 18 months or,until participant reached the age of 2 years (if participant was \<6 months of age at time of enrollment). In addition,rituximab 375 mg/m\^2 IV was administered weekly beginning the day after Myozyme® infusion for 4 weeks(an optional 2nd cycle could be administered at the discretion of the investigator) and biweekly methotrexate 15 mg/m\^2 subcutaneous on the day after Myozyme® infusion for 6 months.
Blood and lymphatic system disorders Neutropenia	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Cardiac disorders Atrial Thrombosis	100.0% 1/1 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Cardiac disorders Cardiac Hypertrophy	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Cardiac disorders Cyanosis	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Cardiac disorders Hypertrophic Cardiomyopathy	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Cardiac disorders Tachycardia	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Gastrointestinal disorders Vomiting	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
General disorders General Physical Health Deterioration	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
General disorders Pyrexia	100.0% 1/1 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Infections and infestations Influenza	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Infections and infestations Pneumonia	100.0% 1/1 • Number of events 4 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Infections and infestations Pneumonia Streptococcal	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Infections and infestations Pneumonia Viral	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Infections and infestations Upper Respiratory Tract Infection	100.0% 1/1 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Blood Pressure Decreased	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Oxygen Saturation Decreased	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Staphylococcus Test Positive	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Metabolism and nutrition disorders Dehydration	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Atelectasis	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Hypercapnia	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Increased Upper Airway Secretion	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	66.7% 2/3 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Cold Sweat	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Urticaria	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Vascular disorders Pallor	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.

Other adverse events

Measure	Regimen A: Alglucosidase Alfa and Cyclophosphamide n=1 participants at risk Participants exhibiting clinical decline since starting alglucosidase alfa (Myozyme®) therapy and having inhibitory antibodies and/or a sustained high rhGAA antibody titer (defined as at least 2 titers \>=25,600 obtained at least 1 month apart), regardless of their CRIM status, were assigned to Regimen A. In Regimen A, participants received alglucosidase alfa (Myozyme®) IV infusion of 20 mg/kg qow for a minimum of 18 months or, until the participant reached the age of 2 years (if the participant was \<6 months of age at the time of enrollment). In addition, cyclophosphamide 250 mg/m\^2 IV infusion was administered q4w after Myozyme® infusion for 6 months.	Regimen B: Alglucosidase Alfa, Rituximab and Methotrexate n=3 participants at risk CRIM-negative participants were assigned to Regimen B if they either(1)exhibited clinical decline since starting alglucosidase alfa (Myozyme®)therapy and did not have inhibitory antibodies and/or a sustained rhGAA antibody titer(defined as at least 2 titers \>=25,600 obtained at least 1 month apart),or(2) did not exhibit clinical decline since starting alglucosidase alfa(Myozyme®) therapy, regardless of their anti-rhGAA or inhibitory antibody status. Regimen B participants with CRIM-negative status received alglucosidase alfa(Myozyme®) IV infusion of 20 mg/kg qow for a minimum of 18 months or,until participant reached the age of 2 years (if participant was \<6 months of age at time of enrollment). In addition,rituximab 375 mg/m\^2 IV was administered weekly beginning the day after Myozyme® infusion for 4 weeks(an optional 2nd cycle could be administered at the discretion of the investigator) and biweekly methotrexate 15 mg/m\^2 subcutaneous on the day after Myozyme® infusion for 6 months.
Renal and urinary disorders Urinary Retention	100.0% 1/1 • Number of events 5 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	100.0% 1/1 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Decubitus Ulcer	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Dermatitis Diaper	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Erythema	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Papule	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Pruritus	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Rash	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Red Man Syndrome	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Skin Discolouration	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Skin Exfoliation	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Skin Irritation	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Skin Swelling	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Skin and subcutaneous tissue disorders Urticaria	100.0% 1/1 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	66.7% 2/3 • Number of events 6 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Vascular disorders Hypertension	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Vascular disorders Hypotension	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Atelectasis	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Dyspnoea	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Increased Bronchial Secretion	100.0% 1/1 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Increased Upper Airway Secretion	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Pneumonia Aspiration	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Vascular disorders Phlebitis	100.0% 1/1 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Pulmonary Oedema	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Cardiac disorders Bradycardia	100.0% 1/1 • Number of events 5 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Cardiac disorders Tachycardia	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Cardiac disorders Ventricular Hypertrophy	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Ear and labyrinth disorders Conductive Deafness	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Ear and labyrinth disorders Deafness Bilateral	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Ear and labyrinth disorders Mixed Deafness	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Eye disorders Conjunctivitis	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Gastrointestinal disorders Abdominal Distension	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Gastrointestinal disorders Constipation	100.0% 1/1 • Number of events 5 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Gastrointestinal disorders Diarrhoea	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Gastrointestinal disorders Faecaloma	100.0% 1/1 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Gastrointestinal disorders Faeces Hard	100.0% 1/1 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Gastrointestinal disorders Nausea	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Gastrointestinal disorders Retching	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Gastrointestinal disorders Vomiting	100.0% 1/1 • Number of events 4 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
General disorders Catheter Site Phlebitis	100.0% 1/1 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
General disorders Medical Device Complication	100.0% 1/1 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
General disorders Oedema Peripheral	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
General disorders Pain	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
General disorders Pyrexia	100.0% 1/1 • Number of events 10 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	66.7% 2/3 • Number of events 10 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
General disorders Thrombosis In Device	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Infections and infestations Bacterial Tracheitis	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Infections and infestations Otitis Media	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	100.0% 3/3 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Infections and infestations Otitis Media Acute	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	66.7% 2/3 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Infections and infestations Pharyngitis	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Infections and infestations Pneumonia	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Infections and infestations Staphylococcal Bacteraemia	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Infections and infestations Tracheitis	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	66.7% 2/3 • Number of events 7 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Infections and infestations Urinary Tract Infection	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Injury, poisoning and procedural complications Arthropod Bite	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Injury, poisoning and procedural complications Excoriation	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Injury, poisoning and procedural complications Feeding Tube Complication	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Injury, poisoning and procedural complications Thermal Burn	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Injury, poisoning and procedural complications Tracheal Haemorrhage	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Alanine Aminotransferase Increased	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Blood Creatine Phosphokinase Mb Increased	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Blood Creatine Phosphokinase Increased	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Blood Immunoglobulin M Increased	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Blood Magnesium Decreased	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Blood Potassium Decreased	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Body Temperature Increased	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	100.0% 3/3 • Number of events 10 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Heart Rate Increased	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 4 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Lymphocyte Count Decreased	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Lymphocyte Percentage Decreased	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Muscle Enzyme Increased	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Neutrophil Count Decreased	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Neutrophil Percentage Increased	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Oxygen Saturation Decreased	100.0% 1/1 • Number of events 3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations Urine Output Decreased	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations White Blood Cell Count Decreased	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	66.7% 2/3 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Investigations White Blood Cells Urine Positive	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Musculoskeletal and connective tissue disorders Joint Contracture	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Nervous system disorders Clonus	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Nervous system disorders Hypokinesia	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	66.7% 2/3 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Psychiatric disorders Agitation	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Psychiatric disorders Insomnia	0.00% 0/1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	33.3% 1/3 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Psychiatric disorders Restlessness	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Renal and urinary disorders Hydronephrosis	100.0% 1/1 • Number of events 1 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.
Renal and urinary disorders Oliguria	100.0% 1/1 • Number of events 2 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.	0.00% 0/3 • All Adverse Events (AEs) were collected from first IMP administration up to 18 months Reported AEs and deaths are treatment-emergent adverse events i.e. AEs that developed/worsened and deaths that occurred during the 'on treatment period' (time from first IMP administration until 18 months). Analysis was performed on safety population.

Additional Information

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