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

Change From Baseline in Urine Hyaline Casts up to Last IMP Administration

时间窗: Baseline (Day 1) and last on-treatment values (up to 454 weeks)

The LOT values were collected at or just prior to the last IMP administration.

Change From Baseline in Urine pH up to Last IMP Administration

时间窗: Baseline (Day 1) and last on-treatment values (up to 454 weeks)

The LOT values were collected at or just prior to the last IMP administration.

Number of Participants With Body Weight Increased/Decreased

时间窗: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks

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.

Number of Participants With Clinically Significant Physical Examination Abnormalities

时间窗: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks

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.

Change From Baseline in Urine BUN up to Last IMP Administration

时间窗: Baseline (Day 1) and last on-treatment values (up to 454 weeks)

Last on-treatment (LOT) values were collected at or just prior to the last IMP administration.

Change From Baseline in Urine Leukocytes [White Blood Cell (WBC)] up to Last IMP Administration

时间窗: Baseline (Day 1) and last on-treatment values (up to 454 weeks)

The LOT values were collected at or just prior to the last IMP administration.

Apparent Volume of Distribution Steady-State (Vss) of Avalglucosidase Alfa

时间窗: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312

Vss was calculated using the following equation: Vz= CLss/λz. The non-compartmental PK analysis was performed.

Number of Participants With Potentially Clinically Significant Abnormalities in Biochemistry

时间窗: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks

Blood samples were collected to determine the clinical chemistry laboratory abnormalities.

Terminal Half-Life (t1/2z) of Avalglucosidase Alfa

时间窗: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312

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.

Apparent Total Body Clearance Steady-State (CLss) of Avalglucosidase Alfa

时间窗: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312

CLss was calculated using the following equation: CLss= dose/AUC. The non-compartmental PK analysis was performed.

Change From Baseline in Urine Specific Gravity up to Last IMP Administration

时间窗: Baseline (Day 1) and last on-treatment values (up to 454 weeks)

The LOT values were collected at or just prior to the last IMP administration.

Time Corresponding to the Last Concentration (Tlast) of Avalglucosidase Alfa

时间窗: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312

Tlast was defined as time corresponding to the last concentration above the limit of quantification, Clast. The non-compartmental PK analysis was performed.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), Infusion Associated Reactions (IARs) and Deaths

时间窗: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks

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.

Number of Participants With Potentially Clinically Significant Abnormalities in Hematology

时间窗: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks

Blood samples were collected to determine the hematology laboratory significant abnormalities.

Number of Participants With Potentially Clinically Significant Vital Signs Abnormalities

时间窗: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks

Participants vital signs were examined to determine the abnormalities. Vital signs included heart rate, systolic and diastolic blood pressure.

Number of Participants With Potentially Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities

时间窗: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks

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.

Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Real Time (AUClast) of Avalglucosidase Alfa

时间窗: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312

AUClast was calculated using the trapezoidal method from time zero to the real time. The non-compartmental PK analysis was performed.

Number of Participants With Antidrug Antibodies (ADA) Status, Positive or Negative

时间窗: From first dose of IMP up to 4 weeks after the last treatment administration of the IMP, a maximum up to 458 weeks

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).

Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa

时间窗: Predose (prior to infusion), end of the infusion and at 1, 4, 8, 12, and 24 hours post-dose on Week 312

Cmax was defined as maximum plasma concentration observed. The non-compartmental pharmacokinetic (PK) analysis was performed.