Avalglucosidase Alfa Extension Study | NCT02032524 | Trialant
NCT02032524
Sponsor
Genzyme, a Sanofi Company
Status
Completed
Last Update Posted
Mar 1, 2024Actual
Enrollment
19Actual
Phase
Phase 2
Conditions
Glycogen Storage Disease Type II Pompe Disease
Interventions
Avalglucosidase Alfa
Countries
United States
Belgium
Denmark
France
Germany
Netherlands
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02032524
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
LTS13769
Secondary IDs
ID
Type
Description
Link
U1111-1147-3439
Other Identifier
UTN
Brief Title
Avalglucosidase Alfa Extension Study
Official Title
An Open-label, Multicenter, Multinational Extension Study of the Long-term Safety and Pharmacokinetics of Repeated Biweekly Infusions of Avalglucosidase Alfa (neoGAA, GZ402666) in Patients With Pompe Disease
Acronym
NEO-EXT
Organization
SanofiINDUSTRY
Status Module
Record Verification Date
Feb 2024
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Feb 27, 2014Actual
Primary Completion Date
Dec 12, 2022Actual
Completion Date
Dec 12, 2022Actual
First Submitted Date
Dec 4, 2013
First Submission Date that Met QC Criteria
Jan 8, 2014
First Posted Date
Jan 10, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Dec 8, 2023
Results First Submitted that Met QC Criteria
Feb 27, 2024
Results First Posted Date
Mar 1, 2024Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Feb 27, 2024
Last Update Posted Date
Mar 1, 2024Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Genzyme, a Sanofi CompanyINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
Primary Objective:
Long-term safety and pharmacokinetics (PK) of avalglucosidase alfa
Secondary Objective:
Long-term effect of avalglucosidase alfa on pharmacodynamic variables
Detailed Description
The planned duration of the study for each participant was initially 6 years. Each participant continued with the study until the participant withdrew, the Investigator withdrew the participant, or the Sponsor terminated the study. An additional follow-up phase began after the participant has completed the 6-year study period, and lasted until avalglucosidase alfa was approved in the participant's country, except in the United Kingdom (UK), Germany and Denmark, where the duration of the additional follow-up phase was up to the approval in the country or limited to a maximum of 2 years, whichever occurred first (ie, for participants in the UK, Germany and Denmark, the total study duration per participant was 8 years at the maximum including the initial 6-year period and the additional 2-year follow-up).
Conditions Module
Conditions
Glycogen Storage Disease Type II Pompe Disease
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
19Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Avalglucosidase Alfa
Experimental
administered intravenously every 2 weeks
Drug: Avalglucosidase Alfa
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Avalglucosidase Alfa
Drug
Pharmaceutical form: lyophilized powder reconstituted for infusion Route of administration: intravenous
Avalglucosidase Alfa
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Infusion Associated Reactions (IARs) and Deaths
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An serious AE (SAE) is any untoward medical occurrence that results: death or life-threatening or inpatient hospitalization or prolongation of existing hospitalization or persistent or significant disability or congenital anomaly or medically important event. TEAEs are defined as AEs that develop or worsen during the on-treatment period (that is, from the time of first dose of IMP up to 4 weeks after the last administration of the IMP). Protocol-defined IARs were defined as AEs that occur during either the infusion or the post-infusion observation period (that is, up to 2 hours or longer following the infusion as per the Investigator's discretion) which were deemed to be related or possibly related to the IMP.
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Number of Participants With Clinically Significant Physical Examination Abnormalities
Physical examination included, at a minimum, an assessment of the participant's general appearance; skin; head, eyes, ears, nose, and throat; examinations of lymph nodes, abdomen, extremities/joints, neurological and mental status; heart and respiratory auscultation; peripheral arterial pulse; and pupil, knee, achilles, and plantar reflexes.
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Biochemistry
Blood samples were collected to determine the clinical chemistry laboratory abnormalities.
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Hematology
Secondary Outcomes
Measure
Description
Time Frame
Change From Baseline in Cross-Sectional Area (CSA) of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (quadriceps, hamstring) and the lower leg muscles (triceps, extensors, fibularis). The measured area of each muscle group, CSA was provided.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion criteria:
Participants with Pompe disease who previously completed an avalglucosidase study.
The participant and/or their parent/legal guardian is willing and able to provide signed informed consent, and the participant, if <18 years of age, was willing to provide assent if deemed able to do so.
The participant (and participant's legal guardian if participant is <18 years of age) must have had the ability to comply with the clinical protocol.
The participant, if female and of childbearing potential, had to have a negative pregnancy test [urine beta-human chorionic gonadotropin] at baseline.
Exclusion criteria:
The participant was concurrently participating in another clinical study using investigational treatment.
The participant, in the opinion of the Investigator, was unable to adhere to the requirements of the study.
The participant had clinically significant organic disease (with the exception of symptoms relating to Pompe disease), including clinically significant cardiovascular, hepatic, pulmonary, neurologic, or renal disease, or other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the Investigator, precluded participation in the study or potentially decreases survival.
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Dimachkie MM, Barohn RJ, Byrne B, Goker-Alpan O, Kishnani PS, Ladha S, Laforet P, Mengel KE, Pena LDM, Sacconi S, Straub V, Trivedi J, Van Damme P, van der Ploeg AT, Vissing J, Young P, Haack KA, Foster M, Gilbert JM, Miossec P, Vitse O, Zhou T, Schoser B; NEO-EXT investigators. Long-term Safety and Efficacy of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease. Neurology. 2022 Aug 1;99(5):e536-e548. doi: 10.1212/WNL.0000000000200746.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
Yes
Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Participants who completed the open-label TDR12857 study were part of this study. This was an open-label study. As prespecified, data were analyzed and presented combinedly for studies TDR12857 and LTS13769.
Recruitment Details
The study was conducted at 17 centers in 7 countries. A total of 21 participants completed the open-label study TDR12857 (NCT01898364). Of which, 19 participants were enrolled in this study. There was no screening period in this study.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 milligram per kilogram (mg/kg) intravenous (IV) infusion every other week (qow) for up to 454 weeks.
FG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Periods
Title
Milestones
Reasons Not Completed
Period 1: TDR12857 Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Nov 25, 2023
Dec 8, 2023
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
No data available
No data is available for this block.
Intervention Browse Module
No data available
No data is available for this block.
N/A
Intervention Model
Single Group Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
GZ402666
neoGAA
Blood samples were collected to determine the hematology laboratory significant abnormalities.
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Change From Baseline in Urine BUN up to Last IMP Administration
Last on-treatment (LOT) values were collected at or just prior to the last IMP administration.
Baseline (Day 1) and last on-treatment values (up to 454 weeks)
Change From Baseline in Urine Hyaline Casts up to Last IMP Administration
The LOT values were collected at or just prior to the last IMP administration.
Baseline (Day 1) and last on-treatment values (up to 454 weeks)
Change From Baseline in Urine Leukocytes [White Blood Cell (WBC)] up to Last IMP Administration
The LOT values were collected at or just prior to the last IMP administration.
Baseline (Day 1) and last on-treatment values (up to 454 weeks)
Change From Baseline in Urine Specific Gravity up to Last IMP Administration
The LOT values were collected at or just prior to the last IMP administration.
Baseline (Day 1) and last on-treatment values (up to 454 weeks)
Change From Baseline in Urine pH up to Last IMP Administration
The LOT values were collected at or just prior to the last IMP administration.
Baseline (Day 1) and last on-treatment values (up to 454 weeks)
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities
Participants vital signs were examined to determine the abnormalities. Vital signs included heart rate, systolic and diastolic blood pressure.
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Number of Participants With Body Weight Increased/Decreased
Body weight was measured in kilograms and collected in the electronic case report forms every 3 months throughout the duration of the study, as well as at the end of study visit.
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Number of Participants With Potentially Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities
Standard 12-lead ECGs were recorded after at least 15 minutes in the supine position using an electrocardiographic device. The following were assessed: heart rate, rhythm, interval between the peaks of successive QRS complexes (RR), interval from the beginning of the P wave until the beginning of the QRS complex (PR), interval from start of the Q wave to the end of the S wave (QRS), interval between the start of the Q wave and the end of the T wave (QT), QT interval corrected for heart rate (QTc) automatic correction evaluation (by the ECG device), QRS axis, R voltage V6, voltage V1, left ventricular hypertrophy criteria, right ventricular hypertrophy criteria, repolarization charges, and overall cardiac impression for each participant.
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Number of Participants With Antidrug Antibodies (ADA) Status, Positive or Negative
ADA negative was defined as ADAs are not detected (that is, negative in screening assay or reactive in screening but negative in confirmatory assay). ADA positive was defined as ADA was detected (that is, an assay signal equal to or greater than the cut-point in the screening assay and was tested positive in the confirmatory assay).
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa
Cmax was defined as maximum plasma concentration observed. The non-compartmental pharmacokinetic (PK) analysis was performed.
Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Real Time (AUClast) of Avalglucosidase Alfa
AUClast was calculated using the trapezoidal method from time zero to the real time. The non-compartmental PK analysis was performed.
Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
Time Corresponding to the Last Concentration (Tlast) of Avalglucosidase Alfa
Tlast was defined as time corresponding to the last concentration above the limit of quantification, Clast. The non-compartmental PK analysis was performed.
Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
Terminal Half-Life (t1/2z) of Avalglucosidase Alfa
t1/2z was calculated according to the following equation: t1/2z = 0.693/λz. Where, λz is the slope of the regression line of the terminal phase of the plasma concentration versus time curve. Half-life was calculated by taking the regression of at least 3 points. The non-compartmental PK analysis was performed.
Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
Apparent Total Body Clearance Steady-State (CLss) of Avalglucosidase Alfa
CLss was calculated using the following equation: CLss= dose/AUC. The non-compartmental PK analysis was performed.
Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
Apparent Volume of Distribution Steady-State (Vss) of Avalglucosidase Alfa
Vss was calculated using the following equation: Vz= CLss/λz. The non-compartmental PK analysis was performed.
Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
Baseline (Day 1) and Weeks 104 and 442
Change From Baseline in Dixon Fat Fraction of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (quadriceps, hamstring) and the lower leg muscles (triceps, extensors, fibularis). Three-point dixon imaging provided quantification of fat content in muscles [fat fraction (FF)].
Baseline (Day 1) and Weeks 104 and 442
Change From Baseline in Index of Real Muscle Mass (IRMM) of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (quadriceps, hamstring) and the lower leg muscles (triceps, extensors, fibularis). The FF was combined with the CSA measurements trophicity to provide an IRMM in mm^2 (that is, IRMM = CSA x [1 - FF]). A negative change from baseline value in IRMM of skeletal muscle MRI indicates muscle loss (worse outcome) and a positive change from baseline value indicates muscle gain (better outcome).
Baseline (Day 1) and Weeks 104 and 442
Change From Baseline in T2 of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (quadriceps, hamstring) and the lower leg muscles (triceps, extensors, fibularis). The T2 multi-slice multi-spin echo and B1 mapping provided a quantitative measure of disease activity (edema, inflammation) within muscles.
Baseline (Day 1) and Weeks 104 and 442
Change From Baseline in T2 With B1 of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (quadriceps, hamstring) and the lower leg muscles (triceps, extensors, fibularis). The T2 multi-slice multi-spin echo and B1 mapping provided a quantitative measure of disease activity (edema, inflammation) within muscles.
Baseline (Day 1) and Weeks 104 and 442
Change From Baseline in Skeletal Muscle Biopsy Up to Week 312
Skeletal muscle needle or open biopsy was performed on the lower extremity (quadriceps) muscle to assess glycogen content. The MRI appearance of the muscle was used to determine the level (axial slice position) that the biopsy procedure should target (avoiding fatty replaced tissue). Glycogen content was measured by histomorphometric analysis or severity grading to determine how effectively avalglucosidase alfa was able to remove glycogen from muscle.
Baseline (Day 1) and Weeks 27, 104, 208, 260 and 312
Change From Baseline in Urinary Glucose Tetrasaccharide (Hex4) Level Up to Week 442
The Hex4, a tetraglucose oligomer, has been shown to be elevated in the urine of participants with Pompe disease. Hence, determination of Hex4 levels may be a means by which the efficacy of treatments were monitored. Urine samples were collected prior to IMP infusion for the assessment of urinary Hex4 concentrations.
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
FG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
FG003
Group 2: Avalglucosidase Alfa 5 mg/kg
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 424 weeks.
FG004
Group 2: Avalglucosidase Alfa 10 mg/kg
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 450 weeks.
FG005
Group 2: Avalglucosidase Alfa 20 mg/kg
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 445 weeks.
FG0004 subjects
FG0013 subjects
FG0023 subjects
FG0034 subjects
FG0044 subjects
FG0056 subjects
COMPLETED
FG0003 subjects
FG0013 subjects
FG0023 subjects
FG0033 subjects
FG0044 subjects
FG0055 subjects
NOT COMPLETED
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0051 subjects
Type
Comment
Reasons
Adverse Event
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Wishes To Withdraw
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Period 2: LTS13769 Study
Type
Comment
Milestone Data
STARTED
Enrolled and treated participants in LTS13769 study.
FG0003 subjects
FG0012 subjectsOnly eligible participants enrolled in LTS13769 study.
FG0023 subjects
FG0033 subjects
FG0043 subjectsOnly eligible participants enrolled in LTS13769 study.
FG0055 subjects
COMPLETED
FG0003 subjects
FG0011 subjects
FG0022 subjects
FG0033 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0011 subjects
FG0021 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG003
The full analysis (FA) set included all participants who received at least 1 complete infusion of investigational medicinal product (IMP).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
BG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
BG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
BG003
Group 2: Avalglucosidase Alfa 5 mg/kg
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 424 weeks.
BG004
Group 2: Avalglucosidase Alfa 10 mg/kg
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 450 weeks.
BG005
Group 2: Avalglucosidase Alfa 20 mg/kg
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 445 weeks.
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0004
BG0013
BG0023
BG0034
BG0044
BG0056
BG00624
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Age at TDR12857 inform consent.
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG003
Sex: Female, Male
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
Female
BG0003
BG0013
BG002
Race/Ethnicity, Customized
Count of Participants
Participants
No
Title
Denominators
Categories
Title
Measurements
White
BG0004
BG0011
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Infusion Associated Reactions (IARs) and Deaths
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An serious AE (SAE) is any untoward medical occurrence that results: death or life-threatening or inpatient hospitalization or prolongation of existing hospitalization or persistent or significant disability or congenital anomaly or medically important event. TEAEs are defined as AEs that develop or worsen during the on-treatment period (that is, from the time of first dose of IMP up to 4 weeks after the last administration of the IMP). Protocol-defined IARs were defined as AEs that occur during either the infusion or the post-infusion observation period (that is, up to 2 hours or longer following the infusion as per the Investigator's discretion) which were deemed to be related or possibly related to the IMP.
The safety analysis set included all participants who received at least 1 complete infusion of IMP.
Posted
Count of Participants
Participants
No
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
OG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
OG003
Group 2: Avalglucosidase Alfa 5 mg/kg
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 424 weeks.
OG004
Group 2: Avalglucosidase Alfa 10 mg/kg
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 450 weeks.
OG005
Group 2: Avalglucosidase Alfa 20 mg/kg
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 445 weeks.
Units
Counts
Participants
OG0004
OG0013
OG0023
OG003
Title
Denominators
Categories
Any TEAEs
Title
Measurements
OG0004
OG0013
OG0023
OG003
Primary
Number of Participants With Clinically Significant Physical Examination Abnormalities
Physical examination included, at a minimum, an assessment of the participant's general appearance; skin; head, eyes, ears, nose, and throat; examinations of lymph nodes, abdomen, extremities/joints, neurological and mental status; heart and respiratory auscultation; peripheral arterial pulse; and pupil, knee, achilles, and plantar reflexes.
The safety analysis set included all participants who received at least 1 complete infusion of IMP.
Posted
Count of Participants
Participants
No
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
OG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
Primary
Number of Participants With Potentially Clinically Significant Abnormalities in Biochemistry
Blood samples were collected to determine the clinical chemistry laboratory abnormalities.
The safety analysis set included all participants who received at least 1 complete infusion of IMP.
Posted
Count of Participants
Participants
No
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
OG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
OG003
Group 2: Avalglucosidase Alfa 5 mg/kg
Primary
Number of Participants With Potentially Clinically Significant Abnormalities in Hematology
Blood samples were collected to determine the hematology laboratory significant abnormalities.
The safety analysis set included all participants who received at least 1 complete infusion of IMP.
Posted
Count of Participants
Participants
No
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
OG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
OG003
Group 2: Avalglucosidase Alfa 5 mg/kg
Primary
Change From Baseline in Urine BUN up to Last IMP Administration
Last on-treatment (LOT) values were collected at or just prior to the last IMP administration.
The safety analysis set included all participants who received at least 1 complete infusion of IMP.
Posted
Mean
Standard Deviation
millimoles per liter (mmol/L)
Baseline (Day 1) and last on-treatment values (up to 454 weeks)
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
OG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
OG003
Group 2: Avalglucosidase Alfa 5 mg/kg
Primary
Change From Baseline in Urine Hyaline Casts up to Last IMP Administration
The LOT values were collected at or just prior to the last IMP administration.
The safety analysis set included all participants who received at least 1 complete infusion of IMP. Only participants with data collected for LOT value are reported.
Posted
Mean
Standard Deviation
casts per low-power field (casts/lpf)
Baseline (Day 1) and last on-treatment values (up to 454 weeks)
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
OG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
OG003
Group 2: Avalglucosidase Alfa 5 mg/kg
Primary
Change From Baseline in Urine Leukocytes [White Blood Cell (WBC)] up to Last IMP Administration
The LOT values were collected at or just prior to the last IMP administration.
The safety analysis set included all participants who received at least 1 complete infusion of IMP. Only participants with data collected for LOT value are reported.
Posted
Mean
Standard Deviation
WBC per high power field (WBC/HPF)
Baseline (Day 1) and last on-treatment values (up to 454 weeks)
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
OG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
OG003
Group 2: Avalglucosidase Alfa 5 mg/kg
Primary
Change From Baseline in Urine Specific Gravity up to Last IMP Administration
The LOT values were collected at or just prior to the last IMP administration.
The safety analysis set included all participants who received at least 1 complete infusion of IMP. Only participants with data collected for LOT value are reported.
Posted
Mean
Standard Deviation
ratio
Baseline (Day 1) and last on-treatment values (up to 454 weeks)
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
OG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
OG003
Group 2: Avalglucosidase Alfa 5 mg/kg
Primary
Change From Baseline in Urine pH up to Last IMP Administration
The LOT values were collected at or just prior to the last IMP administration.
The safety analysis set included all participants who received at least 1 complete infusion of IMP. Only participants with data collected for LOT value are reported.
Posted
Mean
Standard Deviation
pH score
Baseline (Day 1) and last on-treatment values (up to 454 weeks)
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
OG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
OG003
Group 2: Avalglucosidase Alfa 5 mg/kg
Primary
Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities
Participants vital signs were examined to determine the abnormalities. Vital signs included heart rate, systolic and diastolic blood pressure.
The safety analysis set included all participants who received at least 1 complete infusion of IMP.
Posted
Count of Participants
Participants
No
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
OG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
OG003
Primary
Number of Participants With Body Weight Increased/Decreased
Body weight was measured in kilograms and collected in the electronic case report forms every 3 months throughout the duration of the study, as well as at the end of study visit.
The safety analysis set included all participants who received at least 1 complete infusion of IMP.
Posted
Count of Participants
Participants
No
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
OG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
OG003
Primary
Number of Participants With Potentially Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities
Standard 12-lead ECGs were recorded after at least 15 minutes in the supine position using an electrocardiographic device. The following were assessed: heart rate, rhythm, interval between the peaks of successive QRS complexes (RR), interval from the beginning of the P wave until the beginning of the QRS complex (PR), interval from start of the Q wave to the end of the S wave (QRS), interval between the start of the Q wave and the end of the T wave (QT), QT interval corrected for heart rate (QTc) automatic correction evaluation (by the ECG device), QRS axis, R voltage V6, voltage V1, left ventricular hypertrophy criteria, right ventricular hypertrophy criteria, repolarization charges, and overall cardiac impression for each participant.
The safety analysis set included all participants who received at least 1 complete infusion of IMP.
Posted
Count of Participants
Participants
No
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
Primary
Number of Participants With Antidrug Antibodies (ADA) Status, Positive or Negative
ADA negative was defined as ADAs are not detected (that is, negative in screening assay or reactive in screening but negative in confirmatory assay). ADA positive was defined as ADA was detected (that is, an assay signal equal to or greater than the cut-point in the screening assay and was tested positive in the confirmatory assay).
The Pharmacodynamic (PD) analysis set included enrolled participants without any critical deviations related to IMP administration, and for whom any PD data were available.
Posted
Count of Participants
Participants
No
From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
OG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
Primary
Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa
Cmax was defined as maximum plasma concentration observed. The non-compartmental pharmacokinetic (PK) analysis was performed.
The PK analysis set included enrolled participants without any critical deviations related to IMP administration, and for whom any PK data were available. As pre-specified, results for this outcome measure are presented combinedly for all the dosage groups (5, 10 and 20 mg/kg) under the corresponding reporting groups, Group 1: (Avalglucosidase Alfa) and Group 2: (Avalglucosidase Alfa).
Posted
Geometric Mean
Geometric Coefficient of Variation
microgram per milliliter (mcg/mL)
Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 or 10 or 20 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 2: Avalglucosidase Alfa
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 or 10 or 20 mg/kg IV infusion qow for up to 450 weeks.
Units
Counts
Primary
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Real Time (AUClast) of Avalglucosidase Alfa
AUClast was calculated using the trapezoidal method from time zero to the real time. The non-compartmental PK analysis was performed.
The PK analysis set included enrolled participants without any critical deviations related to IMP administration, and for whom any PK data were available. As pre-specified, results for this outcome measure are presented combinedly for all dosage groups (5, 10 and 20 mg/kg) under corresponding reporting groups, Group 1: (Avalglucosidase Alfa) and Group 2: (Avalglucosidase Alfa). Overall Number of Participants Analyzed = Number of participants contributed to the analysis for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
hour*mcg/mL
Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 or 10 or 20 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 2: Avalglucosidase Alfa
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 or 10 or 20 mg/kg IV infusion qow for up to 450 weeks.
Primary
Time Corresponding to the Last Concentration (Tlast) of Avalglucosidase Alfa
Tlast was defined as time corresponding to the last concentration above the limit of quantification, Clast. The non-compartmental PK analysis was performed.
The PK analysis set included enrolled participants without any critical deviations related to IMP administration, and for whom any PK data were available. As pre-specified, results for this outcome measure are presented combinedly for all dosage groups (5, 10 and 20 mg/kg) under corresponding reporting groups, Group 1: (Avalglucosidase Alfa) and Group 2: (Avalglucosidase Alfa). Overall Number of Participants Analyzed = Number of participants contributed to the analysis for this outcome measure.
Posted
Median
Full Range
hour
Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 or 10 or 20 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 2: Avalglucosidase Alfa
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 or 10 or 20 mg/kg IV infusion qow for up to 450 weeks.
Primary
Terminal Half-Life (t1/2z) of Avalglucosidase Alfa
t1/2z was calculated according to the following equation: t1/2z = 0.693/λz. Where, λz is the slope of the regression line of the terminal phase of the plasma concentration versus time curve. Half-life was calculated by taking the regression of at least 3 points. The non-compartmental PK analysis was performed.
The PK analysis set included enrolled participants without any critical deviations related to IMP administration, and for whom any PK data were available. As pre-specified, results for this outcome measure are presented combinedly for all dosage groups (5, 10 and 20 mg/kg) under corresponding reporting groups, Group 1: (Avalglucosidase Alfa) and Group 2: (Avalglucosidase Alfa). Overall Number of Participants Analyzed = Number of participants contributed to the analysis for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
hour
Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 or 10 or 20 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 2: Avalglucosidase Alfa
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 or 10 or 20 mg/kg IV infusion qow for up to 450 weeks.
Primary
Apparent Total Body Clearance Steady-State (CLss) of Avalglucosidase Alfa
CLss was calculated using the following equation: CLss= dose/AUC. The non-compartmental PK analysis was performed.
The PK analysis set included enrolled participants without any critical deviations related to IMP administration, and for whom any PK data were available. As pre-specified, results for this outcome measure are presented combinedly for all dosage groups (5, 10 and 20 mg/kg) under corresponding reporting groups, Group 1: (Avalglucosidase Alfa) and Group 2: (Avalglucosidase Alfa). Overall Number of Participants Analyzed = Number of participants contributed to the analysis for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
liter/hour
Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 or 10 or 20 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 2: Avalglucosidase Alfa
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 or 10 or 20 mg/kg IV infusion qow for up to 450 weeks.
Primary
Apparent Volume of Distribution Steady-State (Vss) of Avalglucosidase Alfa
Vss was calculated using the following equation: Vz= CLss/λz. The non-compartmental PK analysis was performed.
The PK analysis set included enrolled participants without any critical deviations related to IMP administration, and for whom any PK data were available. As pre-specified, results for this outcome measure are presented combinedly for all dosage groups (5, 10 and 20 mg/kg) under corresponding reporting groups, Group 1: (Avalglucosidase Alfa) and Group 2: (Avalglucosidase Alfa). Overall Number of Participants Analyzed = Number of participants contributed to the analysis for this outcome measure.
Posted
Geometric Mean
Geometric Coefficient of Variation
liter
Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 or 10 or 20 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 2: Avalglucosidase Alfa
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 or 10 or 20 mg/kg IV infusion qow for up to 450 weeks.
Secondary
Change From Baseline in Cross-Sectional Area (CSA) of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (quadriceps, hamstring) and the lower leg muscles (triceps, extensors, fibularis). The measured area of each muscle group, CSA was provided.
The PD analysis set included enrolled participants without any critical deviations related to IMP administration, and for whom any PD data were available. Only participants with data collected at specific time points are reported.
Posted
Mean
Standard Deviation
millimeter square (mm^2)
Baseline (Day 1) and Weeks 104 and 442
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
Secondary
Change From Baseline in Dixon Fat Fraction of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (quadriceps, hamstring) and the lower leg muscles (triceps, extensors, fibularis). Three-point dixon imaging provided quantification of fat content in muscles [fat fraction (FF)].
The PD analysis set included enrolled participants without any critical deviations related to IMP administration, and for whom any PD data were available. Only participants with data collected at specific time points are reported.
Posted
Mean
Standard Deviation
percentage (%)
Baseline (Day 1) and Weeks 104 and 442
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
Secondary
Change From Baseline in Index of Real Muscle Mass (IRMM) of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (quadriceps, hamstring) and the lower leg muscles (triceps, extensors, fibularis). The FF was combined with the CSA measurements trophicity to provide an IRMM in mm^2 (that is, IRMM = CSA x [1 - FF]). A negative change from baseline value in IRMM of skeletal muscle MRI indicates muscle loss (worse outcome) and a positive change from baseline value indicates muscle gain (better outcome).
The PD analysis set included enrolled participants without any critical deviations related to IMP administration, and for whom any PD data were available. Only participants with data collected at specific time points are reported.
Posted
Mean
Standard Deviation
mm^2
Baseline (Day 1) and Weeks 104 and 442
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Secondary
Change From Baseline in T2 of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (quadriceps, hamstring) and the lower leg muscles (triceps, extensors, fibularis). The T2 multi-slice multi-spin echo and B1 mapping provided a quantitative measure of disease activity (edema, inflammation) within muscles.
The PD analysis set included enrolled participants without any critical deviations related to IMP administration, and for whom any PD data were available. Only participants with data collected at specific time points are reported.
Posted
Mean
Standard Deviation
milliseconds (ms)
Baseline (Day 1) and Weeks 104 and 442
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
Secondary
Change From Baseline in T2 With B1 of Skeletal Muscle Magnetic Resonance Imaging (MRI) Up to Week 442
Skeletal muscle MRI performed prior to the muscle needle or open biopsy procedure using both qualitative (T1) and quantitative (T2, dixon) modalities to assess disease severity and detect treatment effects. The T1 weighted axial data was analyzed using the mercuri scale, which determines degree of intact muscle and fatty replacement, providing a qualitative measure of overall disease severity. Trophicity changes were evaluated for 5 muscle groups, including the upper leg muscles (quadriceps, hamstring) and the lower leg muscles (triceps, extensors, fibularis). The T2 multi-slice multi-spin echo and B1 mapping provided a quantitative measure of disease activity (edema, inflammation) within muscles.
The PD analysis set included enrolled participants without any critical deviations related to IMP administration, and for whom any PD data were available. Only participants with data collected at specific time points are reported.
Posted
Mean
Standard Deviation
milliseconds (ms)
Baseline (Day 1) and Weeks 104 and 442
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
Secondary
Change From Baseline in Skeletal Muscle Biopsy Up to Week 312
Skeletal muscle needle or open biopsy was performed on the lower extremity (quadriceps) muscle to assess glycogen content. The MRI appearance of the muscle was used to determine the level (axial slice position) that the biopsy procedure should target (avoiding fatty replaced tissue). Glycogen content was measured by histomorphometric analysis or severity grading to determine how effectively avalglucosidase alfa was able to remove glycogen from muscle.
The PD analysis set included enrolled participants without any critical deviations related to IMP administration, and for whom any PD data were available. Only participants with data collected at specific time points are reported.
Posted
Mean
Standard Deviation
percentage of glycogen
Baseline (Day 1) and Weeks 27, 104, 208, 260 and 312
ID
Title
Description
OG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
OG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Secondary
Change From Baseline in Urinary Glucose Tetrasaccharide (Hex4) Level Up to Week 442
The Hex4, a tetraglucose oligomer, has been shown to be elevated in the urine of participants with Pompe disease. Hence, determination of Hex4 levels may be a means by which the efficacy of treatments were monitored. Urine samples were collected prior to IMP infusion for the assessment of urinary Hex4 concentrations.
The PD analysis set included enrolled participants without any critical deviations related to IMP administration, and for whom any PD data were available.
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
OG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
OG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Time Frame
TEAEs data was collected from first dose of IMP up to 4 weeks after the last dose of IMP administration (maximum exposure duration: up to 454 weeks). Death data were collected from first dose of IMP up to the end of the study.
Description
Analysis was performed on the safety analysis set.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Group 1: Avalglucosidase Alfa 5 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 454 weeks.
0
4
3
4
4
4
EG001
Group 1: Avalglucosidase Alfa 10 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 432 weeks.
0
3
1
3
3
3
EG002
Group 1: Avalglucosidase Alfa 20 mg/kg
Participants who were treatment-naïve to alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 421 weeks.
1
3
1
3
3
3
EG003
Group 2: Avalglucosidase Alfa 5 mg/kg
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 5 mg/kg IV infusion qow for up to 424 weeks.
0
4
1
4
4
4
EG004
Group 2: Avalglucosidase Alfa 10 mg/kg
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 10 mg/kg IV infusion qow for up to 450 weeks.
0
4
1
4
4
4
EG005
Group 2: Avalglucosidase Alfa 20 mg/kg
Participants who were previously treated with alglucosidase alfa received avalglucosidase alfa 20 mg/kg IV infusion qow for up to 445 weeks.
0
6
2
6
6
6
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Myocardial Infarction
Cardiac disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG0030 events0 affected4 at risk
EG0040 events0 affected4 at risk
EG0051 events1 affected6 at risk
Myocardial Ischaemia
Cardiac disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Gastric Ulcer
Gastrointestinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Gastrointestinal Haemorrhage
Gastrointestinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Rectal Haemorrhage
Gastrointestinal disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Volvulus
Gastrointestinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Chest Discomfort
General disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Chills
General disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Non-Cardiac Chest Pain
General disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Pyrexia
General disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Cystitis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Infection
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Clavicle Fracture
Injury, poisoning and procedural complications
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Fractured Sacrum
Injury, poisoning and procedural complications
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Lumbar Vertebral Fracture
Injury, poisoning and procedural complications
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Postimplantation Syndrome
Injury, poisoning and procedural complications
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Subcutaneous Haematoma
Injury, poisoning and procedural complications
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Electrocardiogram Q Wave Abnormal
Investigations
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Basal Cell Carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Lung Carcinoma Cell Type Unspecified Stage Iv
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Renal Cell Carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Melanocytic Naevus
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Skin Cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Squamous Cell Carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Cervical Radiculopathy
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0002 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Cognitive Disorder
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG00012 events3 affected4 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Dizziness Postural
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Dysaesthesia
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Headache
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG00015 events3 affected4 at risk
EG00112 events2 affected3 at risk
EG0028 events2 affected3 at risk
EG003
Hyperaesthesia
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0002 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Lethargy
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Migraine
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0014 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Migraine With Aura
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Neuralgia
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0003 events2 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0004 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Sciatica
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0002 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Sedation Complication
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Sensory Loss
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Sinus Headache
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Speech Disorder
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Syncope
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Tension Headache
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Tremor
Nervous system disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Afterbirth Pain
Pregnancy, puerperium and perinatal conditions
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Pregnancy
Pregnancy, puerperium and perinatal conditions
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0014 events2 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Device Occlusion
Product Issues
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Delusional Disorder, Persecutory Type
Psychiatric disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Depression
Psychiatric disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 25.0
Systematic Assessment
EG0007 events2 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Panic Attack
Psychiatric disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0022 events1 affected3 at risk
EG003
Renal Colic
Renal and urinary disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Renal Cyst
Renal and urinary disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Urine Flow Decreased
Renal and urinary disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Balanoposthitis
Reproductive system and breast disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Dysmenorrhoea
Reproductive system and breast disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0014 events2 affected3 at risk
EG0022 events1 affected3 at risk
EG003
Endometrial Thickening
Reproductive system and breast disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Heavy Menstrual Bleeding
Reproductive system and breast disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Ovarian Cyst
Reproductive system and breast disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Pelvic Pain
Reproductive system and breast disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Acute Respiratory Failure
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Allergic Respiratory Symptom
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Asthma
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Choking
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Chronic Respiratory Failure
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0003 events2 affected4 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0004 events3 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Hyperventilation
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Hypoventilation
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Increased Upper Airway Secretion
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Nasal Congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0003 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Oropharyngeal Pain
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected4 at risk
EG0013 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Painful Respiration
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Paranasal Sinus Discomfort
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Pleural Effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Pulmonary Congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Pulmonary Mass
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Respiratory Failure
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Restrictive Pulmonary Disease
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0003 events2 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Sinus Congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Sinus Pain
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Sleep Apnoea Syndrome
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0002 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Tracheal Polyp
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Upper Respiratory Tract Congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Actinic Keratosis
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Dermatitis
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Dermatitis Allergic
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Ecchymosis
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Hand Dermatitis
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Myxoid Cyst
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Palmar Erythema
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Precancerous Skin Lesion
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0002 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0009 events3 affected4 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Rosacea
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Skin Lesion
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Skin Striae
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0011 events1 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Pregnancy Of Partner
Social circumstances
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Flushing
Vascular disorders
MedDRA 25.0
Systematic Assessment
EG0002 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Haematoma
Vascular disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Hot Flush
Vascular disorders
MedDRA 25.0
Systematic Assessment
EG0001 events1 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Hypertension
Vascular disorders
MedDRA 25.0
Systematic Assessment
EG0002 events2 affected4 at risk
EG0010 events0 affected3 at risk
EG0021 events1 affected3 at risk
EG003
Hypotension
Vascular disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0023 events1 affected3 at risk
EG003
Pallor
Vascular disorders
MedDRA 25.0
Systematic Assessment
EG0000 events0 affected4 at risk
EG0010 events0 affected3 at risk
EG0020 events0 affected3 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.