Glycogen Storage Disease Type II-Pompe's Disease
Conditions
Brief summary
This is a multi-stage, phase 2, open-label, multicenter, multinational, ascending dose cohort, repeated intravenous (IV) infusion study of avalglucosidase alfa in pediatric patients with Infantile-Onset Pompe Disease (IOPD) who have been previously treated with alglucosidase alfa for a minimum of 6 months immediately prior to study entry and have demonstrated clinical decline or unsatisfactory clinical response.
Detailed description
The duration of the study for each participant will be up to 9 years and 4 months that will consist of a 14-day screening period, that may be extended to up to 4 weeks in pre-specified situations. This is followed by a 25-week treatment period and an up to a 462-week treatment extension period and a 4-week post-treatment observation period. Cohort 1 and 2 (Cohort 1: avalglucosidase alfa 20 milligrams per kilogram \[mg/kg\], Cohort 2: avalglucosidase alfa 40 mg/kg) will be non-randomized and Cohort 3 (Cohort 3a: avalglucosidase alfa 40 mg/kg \[maximum tolerated dose\] and Cohort 3b: alglucosidase alfa) will be randomized.
Interventions
Pharmaceutical form: powder for concentrate for solution for infusion, Route of administration: IV
Pharmaceutical form: powder for concentrate for solution for infusion, Route of administration: IV
Sponsors
Genzyme, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Months to 17 Years
Healthy volunteers
Yes
Inclusion criteria
* The participants has confirmed acid alpha-glucosidase (GAA) enzyme deficiency from any tissue source. * The participants who has reached legal age of majority as defined by local regulation, or the participant's legal guardian(s) must provide signed informed consent prior to performing any study-related procedures. If the participant is legally minor per local regulations, assent shall be obtained from participants, if applicable. * The participants (and participant's legal guardian if participant is legally minor as defined by local regulation) must have the ability to comply with the clinical protocol. * The participants is less than 18 years old. * The participants, if female and of childbearing potential, must have a negative serum pregnancy test (beta-human chorionic gonadotropin) and must not breastfeeding at screening/Baseline. * The participant has cardiomyopathy at the time of diagnosis: i.e., left ventricular mass index (LVMI) equivalent to mean age specific LVMI plus 2 standard deviations. * The participant has been receiving a stable dose of alglucosidase alfa regularly for a minimum of 6 months immediately prior to study entry. * For participants in Stage 1: The participant has documented evidence of clinical decline in at least 1 of the following parameters related to Pompe Disease and not related to intercurrent illness as assessed by the Investigator: respiratory function, motor skills, and/or cardiac parameters. * For participants in Stage 2: The participant has documented evidence of suboptimal clinical response in at least 1 of the following parameters related to Pompe Disease and not related to intercurrent illness as assessed by the Investigator: respiratory function, motor skills, and/or new onset of ptosis.
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: * The participant has high antibody titer to alglucosidase alfa. * The participant has a high risk for a severe allergic reaction to neoGAA (avalglucosidase alfa). * The participant requires any prohibited concomitant medications (e.g., immune modulatory treatment) for the duration of the study. * The participant has previously participated in any ACT14132 study cohort. * Female participant of childbearing potential not protected by highly effective contraceptive method of birth control and/or who is unwilling or unable to tested for pregnancy. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) | From Baseline to Week 25 | Adverse event (AE): any untoward medical occurrence in participant received study drug \& did not necessarily had to have causal relationship with treatment. TEAEs: AEs developed/worsened in grade/become serious during PAP period (from the time of 1st study drug dose up to Week 25). Serious AE(SAE): any untoward medical occurrence at any dose resulted in death, was life-threatening, required inpatient hospitalization, prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect or was medically important event. TEAEs included SAEs \& non-SAEs. AESI:AE (serious/non-serious) of scientific \& medical concern specific to Sponsor's product/program, for which ongoing monitoring \& immediate notification by Investigator to Sponsor required. |
| PAP: Number of Participants With Infusion-associated Reactions (IARs) | From Baseline to Week 25 | IARs were defined as AESIs that occurred during either the infusion or the observation period following the infusion which were deemed to be related or possibly related to the study drug. Protocol-defined IARs: An AESIs that occurred during either the infusion or the observation period following the infusion which were deemed to be related or possibly related to study drug. Algorithm-defined IARs: any TEAE meeting either 1 or 2 criteria: 1) event occurred from the start of infusion to the end of infusion plus 24 hours, and considered related to study drug, 2) If an AE time component was missing, compared AE Start date with infusion start date and infusion end date. If an AE Start date was between infusion start date and infusion end date plus one day, and it was related to study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PAP: Number of Participants With Anti-drug Antibody (ADA) Response | From Baseline to Week 25 | Anti-drug antibody response was categorized as: Treatment induced ADAs: ADAs developed de novo (seroconversion) following administration of study drug. Treatment boosted ADAs: pre-existing ADAs that were boosted at least two titer steps from Baseline (i.e., 4-fold increase in titers) followed by administration of study drug. |
| PAP: Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa | Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 and 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25 | Cmax is the maximum observed plasma concentration. |
| PAP: Pharmacokinetic Parameter: Time to Achieve Maximum Observed Plasma Concentration (Tmax) of Avalglucosidase Alfa | Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 and 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25 | Tmax is the time to achieve maximum plasma concentration. |
| PAP: Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-last) of Avalglucosidase Alfa | Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 & 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25 | AUC0-last is the area under the plasma concentration versus time curve from time 0 to the time of last quantifiable concentration. |
| PAP: Pharmacokinetic Parameter: Terminal Half-life (t1/2) of Avalglucosidase Alfa | Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 & 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25 | t1/2 is the time required for the plasma concentration of a drug to decrease by half of its initial concentration. |
| PAP: Pharmacokinetic Parameter: Clearance (CL) of Avalglucosidase Alfa | Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 and 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25 | CL is defined as a quantitative measure of the rate at which a drug substance is removed from the body. |
| PAP: Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Avalglucosidase Alfa | Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 & 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25 | Steady state volume of distribution (Vss) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. |
| PAP: Change From Baseline in Gross Motor Function Measure-88 (GMFM-88) Test Scores at Week 25 | Baseline, Week 25 | GMFM-88 was developed specifically to detect quantitative changes in gross motor function. The GMFM-88 consisted of 88 items organized into 5 dimensions; lying and rolling (17 items); sitting (20 items); crawling and kneeling (14 items); standing (13 items) and walking, running and jumping (24 items). Each item was scored on a 4-point Likert scale with scores range: 0= cannot do; 1 = initiates less then \[\<\] 10 percentage \[%\] of the task; 2 = partially completes \[10% to \<100% of the task\] and 3 = task completion. The score for each dimension was expressed as a % of the maximum score for that dimension.Total percentage score was obtained by adding the percentage scores for each dimension and dividing the sum by the total number of dimensions. Total scores ranged from 0% to 100%; where higher scores indicated better motor functions. |
| PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline, Week 25 | GMFCS-E\&R was a 5 level classification system for specific age ranges; observations were performed on 5 levels based on self-initiated movement, with emphasis on sitting, transfers, and mobility: Level I (walks without limitations), Level II (walks with limitations), Level III (walks using a hand-held mobility device), Level IV (self-mobility with limitations; may use powered mobility) and level V (transported in a manual wheel chair) (I to V). The distinctions between levels were based on functional limitations, the need for assistive mobility devices, and to a much lesser extent, quality of movement, and were designed to be meaningful in daily life. The lower level represented good motor functioning and higher level represented low motor functioning. Number of participants in each level of classification at Baseline and Week 25 were reported. |
| PAP: Change From Baseline in Pompe Pediatric Evaluation of Disability Inventory (Pompe-PEDI) Functional Skills Scale: Mobility Domain Test Score-Scaled Score at Week 25 | Baseline, Week 25 | Pompe-PEDI: disease specific version to assess functional capabilities and performance in children with Pompe disease from 2 months through adolescence. It comprised of Functional Skills Scale and Caregiver Assistance Scale; both scales had 3 domains: Self Care, Mobility, and Social Function. Mobility domain was used to measure change in mobility due to changes in muscle strength; consisted of 160 mobility items for participant/legal guardian. The total number of mobility items the child was capable of, was converted to a scaled score with a range of 0 to 100, where scores near "0" indicated low capability and scores near "100" indicated high capability), where higher score was indicative of greater functional ability. Scaled scores were used to interpret individual function and progress over time. |
| PAP: Change From Baseline in Quick Motor Function Test (QMFT) Scores at Week 25 | Baseline, Week 25 | QMFT was observer administered test comprised of 16 items specifically difficult for participants with Pompe disease. Each item was scored on 5-point ordinal scale ranged from 0 to 4 (higher score indicated better outcome). Total QMFT score was obtained by adding the scores of all items and ranged from 0 (unable to perform motor function tests) to 64 (normal muscle function), where higher score indicated better outcome/greater motor function. |
| PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25 | Baseline, Week 25 | Cardiac function was evaluated using LVM Z-score as assessed by echocardiogram in M-mode. Z-Scores indicated the number of standard deviations (SD) from the mean in a normal distribution. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in LVM Z-score. In this OM, absolute scores at Baseline and Week 25 along with Change from Baseline at Week 25 in LVM Z-score were reported. |
| PAP: Change From Baseline in Eyelid Position Measurements: Interpalpebral Fissure Distance (IPFD) - Left Non-Flash and Right Non-Flash at Week 25 | Baseline, Week 25 | IPFD is the widest vertical distance (in millimeters) between the upper eyelid and the lower eyelid when the participant is looking in "primary gaze" (i.e. normal gaze when looking straight forward). Images were taken while the participants was wearing a pair of empty eyeglass frames with millimeters rulers attached as a standardized tool to measure eyelid position without camera flash. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in measured distance. |
| PAP: Change From Baseline in Eyelid Position Measurements: Left and Right Margin Reflex Distance (MRD) at Week 25 | Baseline, Week 25 | The MRD is the vertical distance (in millimeters) between the light reflex and the upper eyelid when the participant was looking in "primary gaze" while fixating on a light source. Images were taken while the participants was wearing a pair of empty eyeglass frames with millimeters rulers attached as a standardized tool to measure eyelid position. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in measured distance. |
| PAP: Change From Baseline in Eyelid Position Measurements Assessed by Margin Pupil Distance (MPD) - Left Non-Flash and Right Non-Flash at Week 25 | Baseline, Week 25 | The MPD is the vertical distance (in millimeters) between the center of the pupil and the upper eyelid margin. Images were taken while the participants was wearing a pair of empty eyeglass frames with millimeters rulers attached as a standardized tool to measure eyelid position without camera flash. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in measured distance. |
| PAP: Change From Baseline in Creatine Kinase Value at Week 25 | Baseline, Week 25 | Change from Baseline in Creatine kinase value (to assess muscle damage) at Week 25 were reported in this OM. |
| ETP: Number of Participants With Treatment Emergent Adverse Events, Serious Treatment Emergent Adverse Events, and Adverse Event of Special Interest | Up to 9 years and 4 months | Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (August 2028). |
| ETP: Number of Participants With Infusion-associated Reactions | Up to 9 years and 4 months | Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (August 2028). |
Countries
France, Japan, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Sciences & Operations
Sanofi
Participant flow
Recruitment details
The study was conducted at 10 active centers in 5 countries. Total of 22 participants were screened between 12 October 2017 and 03 April 2019. None of the participants were screen failed. Participants were assigned to treatment by using interactive response technology system.
Pre-assignment details
Participants in Cohorts 1 received avalglucosidase alfa 20 milligrams per kilogram (mg/kg) every other week (qow) and participants in Cohort 2 received avalglucosidase alfa 40 mg/kg qow. No randomization process was applied for Cohort 1 and 2. Participants in Cohort 3 were randomized (stratified by gender) to receive either avalglucosidase alfa 40 mg/kg qow (3a) or their current stable alglucosidase alfa dose regimen (3b). Data reported based on primary completion date, i.e., 30 September 2019.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Avalglucosidase Alfa 20 mg/kg Avalglucosidase alfa, 20 mg/kg IV infusion qow for 25 weeks in the PAP, followed by same treatment from Week 26 up to Week 371 in extension treatment period (ETP). | 6 |
| Cohort 2: Avalglucosidase Alfa 40 mg/kg Avalglucosidase alfa 40 mg/kg IV infusion qow for 25 weeks in the PAP, followed by same treatment from Week 26 up to Week 371 in ETP. | 5 |
| Cohort 3a: Avalglucosidase Alfa 40 mg//kg After determination of the highest tolerated avalglucosidase alfa dose in Cohort 1 and Cohort 2 (after at least 5 participants in each Cohort 1 and Cohort 2 had received the 7th dose of avalglucosidase alfa or completed Week 13 with a minimum of 6 infusions), participants received avalglucosidase alfa 40 mg/kg (the highest tolerated dose) IV infusion qow for 25 weeks in PAP, followed by same treatment from Week 26 up to Week 371 in ETP. | 5 |
| Cohort 3b: Alglucosidase Alfa in PAP After determination of the highest tolerated avalglucosidase alfa dose in Cohort 1 and Cohort 2 (after at least 5 participants in each Cohort 1 and Cohort 2 had received the 7th dose of avalglucosidase alfa or completed Week 13 with a minimum of 6 infusions), participants received alglucosidase alfa at their current stable dose (defined as dose \[between 20 mg/kg qow and 40 mg/kg weekly as per physician\] administered regularly for a minimum of 6 months immediately prior to entry in this study) IV infusion for 25 weeks in PAP. After PAP, participants received avalglucosidase alfa 40mg/kg IV infusion qow from Week 26 up to Week 371 in ETP. | 6 |
| Total | 22 |
Baseline characteristics
| Characteristic | Total | Cohort 3b: Alglucosidase Alfa in PAP | Cohort 3a: Avalglucosidase Alfa 40 mg//kg | Cohort 1: Avalglucosidase Alfa 20 mg/kg | Cohort 2: Avalglucosidase Alfa 40 mg/kg |
|---|---|---|---|---|---|
| Age, Continuous | 6.8 years STANDARD_DEVIATION 3.4 | 4.7 years STANDARD_DEVIATION 3.2 | 6.9 years STANDARD_DEVIATION 2.7 | 7.6 years STANDARD_DEVIATION 3.4 | 8.1 years STANDARD_DEVIATION 4.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 0 Participants | 2 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 4 Participants | 3 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Female | 10 Participants | 4 Participants | 3 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 12 Participants | 2 Participants | 2 Participants | 5 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 6 | 0 / 10 | 0 / 3 |
| other Total, other adverse events | 5 / 6 | 5 / 5 | 5 / 5 | 4 / 6 | 6 / 6 | 7 / 10 | 3 / 3 |
| serious Total, serious adverse events | 1 / 6 | 3 / 5 | 0 / 5 | 2 / 6 | 4 / 6 | 2 / 10 | 1 / 3 |
Outcome results
Primary
PAP: Number of Participants With Infusion-associated Reactions (IARs)
IARs were defined as AESIs that occurred during either the infusion or the observation period following the infusion which were deemed to be related or possibly related to the study drug. Protocol-defined IARs: An AESIs that occurred during either the infusion or the observation period following the infusion which were deemed to be related or possibly related to study drug. Algorithm-defined IARs: any TEAE meeting either 1 or 2 criteria: 1) event occurred from the start of infusion to the end of infusion plus 24 hours, and considered related to study drug, 2) If an AE time component was missing, compared AE Start date with infusion start date and infusion end date. If an AE Start date was between infusion start date and infusion end date plus one day, and it was related to study drug.
Time frame: From Baseline to Week 25
Population: Analysis was performed on safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants With Infusion-associated Reactions (IARs) | Protocol-defined IARs | 0 Participants |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants With Infusion-associated Reactions (IARs) | Algorithm-defined IARs | 0 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants With Infusion-associated Reactions (IARs) | Algorithm-defined IARs | 2 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants With Infusion-associated Reactions (IARs) | Protocol-defined IARs | 2 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants With Infusion-associated Reactions (IARs) | Protocol-defined IARs | 1 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants With Infusion-associated Reactions (IARs) | Algorithm-defined IARs | 1 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants With Infusion-associated Reactions (IARs) | Protocol-defined IARs | 1 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants With Infusion-associated Reactions (IARs) | Algorithm-defined IARs | 1 Participants |
Primary
PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI)
Adverse event (AE): any untoward medical occurrence in participant received study drug & did not necessarily had to have causal relationship with treatment. TEAEs: AEs developed/worsened in grade/become serious during PAP period (from the time of 1st study drug dose up to Week 25). Serious AE(SAE): any untoward medical occurrence at any dose resulted in death, was life-threatening, required inpatient hospitalization, prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect or was medically important event. TEAEs included SAEs & non-SAEs. AESI:AE (serious/non-serious) of scientific & medical concern specific to Sponsor's product/program, for which ongoing monitoring & immediate notification by Investigator to Sponsor required.
Time frame: From Baseline to Week 25
Population: Analysis was performed on safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) | Any TEAEs | 5 Participants |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) | Any AESI | 0 Participants |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) | Any Serious TEAEs | 1 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) | Any TEAEs | 5 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) | Any AESI | 2 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) | Any Serious TEAEs | 3 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) | Any TEAEs | 5 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) | Any AESI | 1 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) | Any Serious TEAEs | 0 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) | Any TEAEs | 5 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) | Any Serious TEAEs | 2 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) | Any AESI | 1 Participants |
Secondary
ETP: Number of Participants With Infusion-associated Reactions
Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2027).
Time frame: Up to 8 years and 9 months
Secondary
ETP: Number of Participants With Treatment Emergent Adverse Events, Serious Treatment Emergent Adverse Events, and Adverse Event of Special Interest
Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2027).
Time frame: Up to 8 years and 9 months
Secondary
PAP: Change From Baseline in Creatine Kinase Value at Week 25
Change from Baseline in Creatine kinase value (to assess muscle damage) at Week 25 were reported in this OM.
Time frame: Baseline, Week 25
Population: Analysis was performed on safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Change From Baseline in Creatine Kinase Value at Week 25 | -208.67 international units per liters | Standard Deviation 382.34 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Creatine Kinase Value at Week 25 | -476.60 international units per liters | Standard Deviation 467.2 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Creatine Kinase Value at Week 25 | -421.40 international units per liters | Standard Deviation 413.39 |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Change From Baseline in Creatine Kinase Value at Week 25 | -1.33 international units per liters | Standard Deviation 51.2 |
Secondary
PAP: Change From Baseline in Eyelid Position Measurements Assessed by Margin Pupil Distance (MPD) - Left Non-Flash and Right Non-Flash at Week 25
The MPD is the vertical distance (in millimeters) between the center of the pupil and the upper eyelid margin. Images were taken while the participants was wearing a pair of empty eyeglass frames with millimeters rulers attached as a standardized tool to measure eyelid position without camera flash. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in measured distance.
Time frame: Baseline, Week 25
Population: Analysis was performed on safety population. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements Assessed by Margin Pupil Distance (MPD) - Left Non-Flash and Right Non-Flash at Week 25 | MPD Right Non-Flash | -0.25 millimeters | Standard Deviation 1.41 |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements Assessed by Margin Pupil Distance (MPD) - Left Non-Flash and Right Non-Flash at Week 25 | MPD Left Non-Flash | -0.83 millimeters | Standard Deviation 1.44 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements Assessed by Margin Pupil Distance (MPD) - Left Non-Flash and Right Non-Flash at Week 25 | MPD Left Non-Flash | 0.75 millimeters | Standard Deviation 1.19 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements Assessed by Margin Pupil Distance (MPD) - Left Non-Flash and Right Non-Flash at Week 25 | MPD Right Non-Flash | 0.50 millimeters | Standard Deviation 1.06 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements Assessed by Margin Pupil Distance (MPD) - Left Non-Flash and Right Non-Flash at Week 25 | MPD Left Non-Flash | 0.40 millimeters | Standard Deviation 0.42 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements Assessed by Margin Pupil Distance (MPD) - Left Non-Flash and Right Non-Flash at Week 25 | MPD Right Non-Flash | 0.30 millimeters | Standard Deviation 0.91 |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Change From Baseline in Eyelid Position Measurements Assessed by Margin Pupil Distance (MPD) - Left Non-Flash and Right Non-Flash at Week 25 | MPD Left Non-Flash | -0.50 millimeters | Standard Deviation 0.32 |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Change From Baseline in Eyelid Position Measurements Assessed by Margin Pupil Distance (MPD) - Left Non-Flash and Right Non-Flash at Week 25 | MPD Right Non-Flash | 0.00 millimeters | Standard Deviation 0.71 |
Secondary
PAP: Change From Baseline in Eyelid Position Measurements: Interpalpebral Fissure Distance (IPFD) - Left Non-Flash and Right Non-Flash at Week 25
IPFD is the widest vertical distance (in millimeters) between the upper eyelid and the lower eyelid when the participant is looking in primary gaze (i.e. normal gaze when looking straight forward). Images were taken while the participants was wearing a pair of empty eyeglass frames with millimeters rulers attached as a standardized tool to measure eyelid position without camera flash. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in measured distance.
Time frame: Baseline, Week 25
Population: Analysis was performed on safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements: Interpalpebral Fissure Distance (IPFD) - Left Non-Flash and Right Non-Flash at Week 25 | Right non-Flash | -0.92 millimeters | Standard Deviation 1.66 |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements: Interpalpebral Fissure Distance (IPFD) - Left Non-Flash and Right Non-Flash at Week 25 | Left non-Flash | -0.67 millimeters | Standard Deviation 1.54 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements: Interpalpebral Fissure Distance (IPFD) - Left Non-Flash and Right Non-Flash at Week 25 | Right non-Flash | 0.70 millimeters | Standard Deviation 1.25 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements: Interpalpebral Fissure Distance (IPFD) - Left Non-Flash and Right Non-Flash at Week 25 | Left non-Flash | 1.30 millimeters | Standard Deviation 1.48 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements: Interpalpebral Fissure Distance (IPFD) - Left Non-Flash and Right Non-Flash at Week 25 | Left non-Flash | 1.30 millimeters | Standard Deviation 0.76 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements: Interpalpebral Fissure Distance (IPFD) - Left Non-Flash and Right Non-Flash at Week 25 | Right non-Flash | 0.90 millimeters | Standard Deviation 1.14 |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Change From Baseline in Eyelid Position Measurements: Interpalpebral Fissure Distance (IPFD) - Left Non-Flash and Right Non-Flash at Week 25 | Left non-Flash | -0.50 millimeters | Standard Deviation 0.77 |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Change From Baseline in Eyelid Position Measurements: Interpalpebral Fissure Distance (IPFD) - Left Non-Flash and Right Non-Flash at Week 25 | Right non-Flash | -0.25 millimeters | Standard Deviation 1.13 |
Secondary
PAP: Change From Baseline in Eyelid Position Measurements: Left and Right Margin Reflex Distance (MRD) at Week 25
The MRD is the vertical distance (in millimeters) between the light reflex and the upper eyelid when the participant was looking in primary gaze while fixating on a light source. Images were taken while the participants was wearing a pair of empty eyeglass frames with millimeters rulers attached as a standardized tool to measure eyelid position. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in measured distance.
Time frame: Baseline, Week 25
Population: Analysis was performed on safety population. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements: Left and Right Margin Reflex Distance (MRD) at Week 25 | Left MRD | -0.08 millimeters | Standard Deviation 1.53 |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements: Left and Right Margin Reflex Distance (MRD) at Week 25 | Right MRD | -0.50 millimeters | Standard Deviation 1.61 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements: Left and Right Margin Reflex Distance (MRD) at Week 25 | Right MRD | -0.50 millimeters | Standard Deviation 1.27 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements: Left and Right Margin Reflex Distance (MRD) at Week 25 | Left MRD | -0.38 millimeters | Standard Deviation 0.85 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements: Left and Right Margin Reflex Distance (MRD) at Week 25 | Left MRD | 0.88 millimeters | Standard Deviation 1.11 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Eyelid Position Measurements: Left and Right Margin Reflex Distance (MRD) at Week 25 | Right MRD | 0.63 millimeters | Standard Deviation 1.03 |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Change From Baseline in Eyelid Position Measurements: Left and Right Margin Reflex Distance (MRD) at Week 25 | Left MRD | 0.08 millimeters | Standard Deviation 0.74 |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Change From Baseline in Eyelid Position Measurements: Left and Right Margin Reflex Distance (MRD) at Week 25 | Right MRD | -0.08 millimeters | Standard Deviation 0.74 |
Secondary
PAP: Change From Baseline in Gross Motor Function Measure-88 (GMFM-88) Test Scores at Week 25
GMFM-88 was developed specifically to detect quantitative changes in gross motor function. The GMFM-88 consisted of 88 items organized into 5 dimensions; lying and rolling (17 items); sitting (20 items); crawling and kneeling (14 items); standing (13 items) and walking, running and jumping (24 items). Each item was scored on a 4-point Likert scale with scores range: 0= cannot do; 1 = initiates less then \[\<\] 10 percentage \[%\] of the task; 2 = partially completes \[10% to \<100% of the task\] and 3 = task completion. The score for each dimension was expressed as a % of the maximum score for that dimension.Total percentage score was obtained by adding the percentage scores for each dimension and dividing the sum by the total number of dimensions. Total scores ranged from 0% to 100%; where higher scores indicated better motor functions.
Time frame: Baseline, Week 25
Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this OM.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Change From Baseline in Gross Motor Function Measure-88 (GMFM-88) Test Scores at Week 25 | 6.50 percentage of total score | Standard Deviation 22.24 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Gross Motor Function Measure-88 (GMFM-88) Test Scores at Week 25 | 9.80 percentage of total score | Standard Deviation 13.99 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Gross Motor Function Measure-88 (GMFM-88) Test Scores at Week 25 | 11.00 percentage of total score | Standard Deviation 10.8 |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Change From Baseline in Gross Motor Function Measure-88 (GMFM-88) Test Scores at Week 25 | 17.00 percentage of total score | Standard Deviation 8.44 |
Secondary
PAP: Change From Baseline in Pompe Pediatric Evaluation of Disability Inventory (Pompe-PEDI) Functional Skills Scale: Mobility Domain Test Score-Scaled Score at Week 25
Pompe-PEDI: disease specific version to assess functional capabilities and performance in children with Pompe disease from 2 months through adolescence. It comprised of Functional Skills Scale and Caregiver Assistance Scale; both scales had 3 domains: Self Care, Mobility, and Social Function. Mobility domain was used to measure change in mobility due to changes in muscle strength; consisted of 160 mobility items for participant/legal guardian. The total number of mobility items the child was capable of, was converted to a scaled score with a range of 0 to 100, where scores near 0 indicated low capability and scores near 100 indicated high capability), where higher score was indicative of greater functional ability. Scaled scores were used to interpret individual function and progress over time.
Time frame: Baseline, Week 25
Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this OM.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Change From Baseline in Pompe Pediatric Evaluation of Disability Inventory (Pompe-PEDI) Functional Skills Scale: Mobility Domain Test Score-Scaled Score at Week 25 | 6.19 score on a scale | Standard Deviation 10.55 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Pompe Pediatric Evaluation of Disability Inventory (Pompe-PEDI) Functional Skills Scale: Mobility Domain Test Score-Scaled Score at Week 25 | 2.12 score on a scale | Standard Deviation 4.04 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Pompe Pediatric Evaluation of Disability Inventory (Pompe-PEDI) Functional Skills Scale: Mobility Domain Test Score-Scaled Score at Week 25 | 2.60 score on a scale | Standard Deviation 1.72 |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Change From Baseline in Pompe Pediatric Evaluation of Disability Inventory (Pompe-PEDI) Functional Skills Scale: Mobility Domain Test Score-Scaled Score at Week 25 | 5.20 score on a scale | Standard Deviation 5.95 |
Secondary
PAP: Change From Baseline in Quick Motor Function Test (QMFT) Scores at Week 25
QMFT was observer administered test comprised of 16 items specifically difficult for participants with Pompe disease. Each item was scored on 5-point ordinal scale ranged from 0 to 4 (higher score indicated better outcome). Total QMFT score was obtained by adding the scores of all items and ranged from 0 (unable to perform motor function tests) to 64 (normal muscle function), where higher score indicated better outcome/greater motor function.
Time frame: Baseline, Week 25
Population: Analysis was performed on safety population. Here, 'overall number of participants analyzed' = participants with available data for this OM.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Change From Baseline in Quick Motor Function Test (QMFT) Scores at Week 25 | -0.17 score on a scale | Standard Deviation 4.45 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Quick Motor Function Test (QMFT) Scores at Week 25 | 3.20 score on a scale | Standard Deviation 4.55 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Change From Baseline in Quick Motor Function Test (QMFT) Scores at Week 25 | 4.25 score on a scale | Standard Deviation 3.3 |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Change From Baseline in Quick Motor Function Test (QMFT) Scores at Week 25 | 5.17 score on a scale | Standard Deviation 4.54 |
Secondary
PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25
Cardiac function was evaluated using LVM Z-score as assessed by echocardiogram in M-mode. Z-Scores indicated the number of standard deviations (SD) from the mean in a normal distribution. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in LVM Z-score. In this OM, absolute scores at Baseline and Week 25 along with Change from Baseline at Week 25 in LVM Z-score were reported.
Time frame: Baseline, Week 25
Population: Analysis was performed on safety population. Here, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25 | Baseline | -1.10 Z-score | Standard Deviation 1.07 |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25 | Change from Baseline at Week 25 | -0.60 Z-score | Standard Deviation 2.16 |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25 | Week 25 | -1.74 Z-score | Standard Deviation 2.01 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25 | Baseline | 0.13 Z-score | Standard Deviation 2.39 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25 | Change from Baseline at Week 25 | -0.60 Z-score | Standard Deviation 0.71 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25 | Week 25 | -1.05 Z-score | Standard Deviation 2.61 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25 | Week 25 | -1.36 Z-score | Standard Deviation 0.99 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25 | Baseline | -0.78 Z-score | Standard Deviation 0.7 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25 | Change from Baseline at Week 25 | -0.58 Z-score | Standard Deviation 0.76 |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25 | Baseline | -0.43 Z-score | Standard Deviation 0.92 |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25 | Change from Baseline at Week 25 | 0.47 Z-score | Standard Deviation 1.76 |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25 | Week 25 | 0.15 Z-score | Standard Deviation 1.07 |
Secondary
PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25
GMFCS-E&R was a 5 level classification system for specific age ranges; observations were performed on 5 levels based on self-initiated movement, with emphasis on sitting, transfers, and mobility: Level I (walks without limitations), Level II (walks with limitations), Level III (walks using a hand-held mobility device), Level IV (self-mobility with limitations; may use powered mobility) and level V (transported in a manual wheel chair) (I to V). The distinctions between levels were based on functional limitations, the need for assistive mobility devices, and to a much lesser extent, quality of movement, and were designed to be meaningful in daily life. The lower level represented good motor functioning and higher level represented low motor functioning. Number of participants in each level of classification at Baseline and Week 25 were reported.
Time frame: Baseline, Week 25
Population: Analysis was performed on safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level I | 1 Participants |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level III | 1 Participants |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level IV | 2 Participants |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level II | 1 Participants |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level II | 1 Participants |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level III | 2 Participants |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level IV | 1 Participants |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level V | 1 Participants |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level V | 1 Participants |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level I | 1 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level IV | 2 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level III | 1 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level I | 1 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level II | 2 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level V | 0 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level IV | 1 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level I | 1 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level II | 2 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level III | 0 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level V | 0 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level II | 1 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level I | 2 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level II | 1 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level III | 1 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level I | 2 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level IV | 0 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level V | 1 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level III | 0 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level IV | 1 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level V | 1 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level I | 3 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level II | 0 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level III | 1 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level IV | 1 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level II | 0 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Baseline: Level V | 1 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level III | 1 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level IV | 1 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level V | 1 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 | Week 25: Level I | 3 Participants |
Secondary
PAP: Number of Participants With Anti-drug Antibody (ADA) Response
Anti-drug antibody response was categorized as: Treatment induced ADAs: ADAs developed de novo (seroconversion) following administration of study drug. Treatment boosted ADAs: pre-existing ADAs that were boosted at least two titer steps from Baseline (i.e., 4-fold increase in titers) followed by administration of study drug.
Time frame: From Baseline to Week 25
Population: Analysis was performed on the ADA evaluable population which included participants who had received at least 1 infusion (partial or total) and had at least one ADA sample taken post-baseline after drug administration that was appropriate for ADA testing with a reportable result.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants With Anti-drug Antibody (ADA) Response | Treatment boosted ADA response | 0 Participants |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Number of Participants With Anti-drug Antibody (ADA) Response | Treatment induced ADA response | 0 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants With Anti-drug Antibody (ADA) Response | Treatment induced ADA response | 1 Participants |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants With Anti-drug Antibody (ADA) Response | Treatment boosted ADA response | 0 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants With Anti-drug Antibody (ADA) Response | Treatment boosted ADA response | 1 Participants |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Number of Participants With Anti-drug Antibody (ADA) Response | Treatment induced ADA response | 3 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants With Anti-drug Antibody (ADA) Response | Treatment boosted ADA response | 2 Participants |
| PAP: Cohort 3b: Alglucosidase Alfa | PAP: Number of Participants With Anti-drug Antibody (ADA) Response | Treatment induced ADA response | 1 Participants |
Secondary
PAP: Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-last) of Avalglucosidase Alfa
AUC0-last is the area under the plasma concentration versus time curve from time 0 to the time of last quantifiable concentration.
Time frame: Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 & 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25
Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data for each specified category. Data for this OM was not planned to be collected and analyzed for PAP: Cohort 3b: Alglucosidase Alfa arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-last) of Avalglucosidase Alfa | Week 1 | 923000 nanograms*hours per milliliter | Standard Deviation 352000 |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-last) of Avalglucosidase Alfa | Week 25 | 805000 nanograms*hours per milliliter | Standard Deviation 295000 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-last) of Avalglucosidase Alfa | Week 1 | 2630000 nanograms*hours per milliliter | Standard Deviation 972000 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-last) of Avalglucosidase Alfa | Week 25 | 1930000 nanograms*hours per milliliter | Standard Deviation 348000 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-last) of Avalglucosidase Alfa | Week 25 | 2200000 nanograms*hours per milliliter | Standard Deviation 533000 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-last) of Avalglucosidase Alfa | Week 1 | 1720000 nanograms*hours per milliliter | Standard Deviation 255000 |
Secondary
PAP: Pharmacokinetic Parameter: Clearance (CL) of Avalglucosidase Alfa
CL is defined as a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 and 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25
Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data for each specified category. Data for this OM was not planned to be collected and analyzed for PAP: Cohort 3b: Alglucosidase Alfa arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Pharmacokinetic Parameter: Clearance (CL) of Avalglucosidase Alfa | Week 25 | 696 milliliters per hours | Standard Deviation 203 |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Pharmacokinetic Parameter: Clearance (CL) of Avalglucosidase Alfa | Week 1 | 673 milliliters per hours | Standard Deviation 222 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Clearance (CL) of Avalglucosidase Alfa | Week 25 | 683 milliliters per hours | Standard Deviation 345 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Clearance (CL) of Avalglucosidase Alfa | Week 1 | 562 milliliters per hours | Standard Deviation 152 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Clearance (CL) of Avalglucosidase Alfa | Week 1 | 529 milliliters per hours | Standard Deviation 150 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Clearance (CL) of Avalglucosidase Alfa | Week 25 | 526 milliliters per hours | Standard Deviation 125 |
Secondary
PAP: Pharmacokinetic Parameter: Terminal Half-life (t1/2) of Avalglucosidase Alfa
t1/2 is the time required for the plasma concentration of a drug to decrease by half of its initial concentration.
Time frame: Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 & 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25
Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data for each specified category. Data for this OM was not planned to be collected and analyzed for PAP: Cohort 3b: Alglucosidase Alfa arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Pharmacokinetic Parameter: Terminal Half-life (t1/2) of Avalglucosidase Alfa | Week 1 | 0.703 hours | Standard Deviation 0.291 |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Pharmacokinetic Parameter: Terminal Half-life (t1/2) of Avalglucosidase Alfa | Week 25 | 0.601 hours | Standard Deviation 0.256 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Terminal Half-life (t1/2) of Avalglucosidase Alfa | Week 1 | 1.15 hours | Standard Deviation 0.523 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Terminal Half-life (t1/2) of Avalglucosidase Alfa | Week 25 | 1.04 hours | Standard Deviation 0.248 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Terminal Half-life (t1/2) of Avalglucosidase Alfa | Week 1 | 0.806 hours | Standard Deviation 0.248 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Terminal Half-life (t1/2) of Avalglucosidase Alfa | Week 25 | 1.19 hours | Standard Deviation 0.472 |
Secondary
PAP: Pharmacokinetic Parameter: Time to Achieve Maximum Observed Plasma Concentration (Tmax) of Avalglucosidase Alfa
Tmax is the time to achieve maximum plasma concentration.
Time frame: Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 and 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25
Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data for each specified category. Data for this OM was not planned to be collected and analyzed for PAP: Cohort 3b: Alglucosidase Alfa arm.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Pharmacokinetic Parameter: Time to Achieve Maximum Observed Plasma Concentration (Tmax) of Avalglucosidase Alfa | Week 1 | 4.43 hours |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Pharmacokinetic Parameter: Time to Achieve Maximum Observed Plasma Concentration (Tmax) of Avalglucosidase Alfa | Week 25 | 3.97 hours |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Time to Achieve Maximum Observed Plasma Concentration (Tmax) of Avalglucosidase Alfa | Week 1 | 7.00 hours |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Time to Achieve Maximum Observed Plasma Concentration (Tmax) of Avalglucosidase Alfa | Week 25 | 7.13 hours |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Time to Achieve Maximum Observed Plasma Concentration (Tmax) of Avalglucosidase Alfa | Week 1 | 6.83 hours |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Time to Achieve Maximum Observed Plasma Concentration (Tmax) of Avalglucosidase Alfa | Week 25 | 6.87 hours |
Secondary
PAP: Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Avalglucosidase Alfa
Steady state volume of distribution (Vss) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time frame: Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 & 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25
Population: Analysis was performed on PK population. Here, 'number analyzed' = participants with available data for each specified category. Data for this OM was not planned to be collected and analyzed for PAP: Cohort 3b: Alglucosidase Alfa arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Avalglucosidase Alfa | Week 1 | 3550 milliliters | Standard Deviation 927 |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Avalglucosidase Alfa | Week 25 | 3520 milliliters | Standard Deviation 1180 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Avalglucosidase Alfa | Week 25 | 5350 milliliters | Standard Deviation 2270 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Avalglucosidase Alfa | Week 1 | 4500 milliliters | Standard Deviation 882 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Avalglucosidase Alfa | Week 1 | 4300 milliliters | Standard Deviation 1420 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Avalglucosidase Alfa | Week 25 | 4020 milliliters | Standard Deviation 1390 |
Secondary
PAP: Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa
Cmax is the maximum observed plasma concentration.
Time frame: Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 and 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25
Population: Analysis was performed on PK population which included PAP participants who had received at least 1 infusion (partial or total) and had evaluable drug concentration data. Here, 'number analyzed' = participants with available data for each specified category. Data for this OM was not planned to be collected and analyzed for PAP: Cohort 3b: Alglucosidase Alfa arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa | Week 1 | 189000 nanograms per milliliter | Standard Deviation 56700 |
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa | Week 25 | 175000 nanograms per milliliter | Standard Deviation 65900 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa | Week 1 | 403000 nanograms per milliliter | Standard Deviation 171000 |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa | Week 25 | 297000 nanograms per milliliter | Standard Deviation 60100 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa | Week 1 | 250000 nanograms per milliliter | Standard Deviation 45100 |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa | Week 25 | 356000 nanograms per milliliter | Standard Deviation 84700 |