Pompe Disease (Late-onset)
Conditions
Keywords
Pompe, rhGAA
Brief summary
This is a phase 3 double-blind randomized study to study the efficacy and safety of intravenous ATB200 Co-administered with oral AT2221 in adult subjects with Late Onset Pompe Disease compared with Alglucosidase Alfa/placebo.
Detailed description
This is a double-blind, randomized, multicenter, international study of ATB200/AT2221 in adult subjects with late-onset Pompe disease (LOPD) who have received enzyme replacement therapy with alglucosidase alfa (ie, ERT-experienced) or who have never received ERT (ie, ERT naïve) compared with alglucosidase alfa/placebo. The study will consist of a screening period up to 30 days, a 12-month treatment period, and a 30 day safety follow-up period. Subjects who complete this study will have the option to participate in an open label extension study to receive ATB200/AT2221 under a separate protocol. Enzyme replacement therapy-experienced subjects will continue to take alglucosidase alfa during the screening period; treatment with alglucosidase alfa will then be replaced by study drug (ATB200/AT2221 or alglucosidase alfa/placebo) on the same schedule without interruption (ie, every 2 weeks). Infusion visits will be scheduled every 2 weeks throughout the study; assessments (eg, clinical laboratory tests) for initial safety monitoring will be performed at these visits for the first 6 weeks of the study. Study visits that include efficacy, safety, and other assessments will be scheduled approximately every 3 months and may occur over 2 days, provided all study assessments and procedures (with the exception of pharmacokinetic \[PK\] sample collection) are performed before administration of study drug. Efficacy assessments (ie, functional assessments) include evaluation of ambulatory function (6MWT), motor function tests (Gait, Stair, Gowers' maneuver, and Chair \[GSGC\] test and Timed Up and Go \[TUG\] test), muscle strength (manual muscle testing and quantitative muscle testing), and pulmonary function tests (forced vital capacity \[FVC\], slow vital capacity \[SVC\], maximal inspiratory pressure \[MIP\], maximal expiratory pressure \[MEP\], and sniff nasal inspiratory pressure \[SNIP\]). Patient reported outcomes (Rasch-built Pompe-specific Activity \[R PAct\] Scale, EuroQol 5 Dimensions 5 Levels Instrument \[EQ-5D-5L\], Patient-Reported Outcomes Measurement Information System \[PROMIS®\] instruments for physical function, fatigue, dyspnea, and upper extremity, and Subject's Global Impression of Change). The Physician's Global Impression of Change will also be performed. Pharmacodynamic assessments include measurement of biomarkers of muscle injury (creatine kinase \[CK\]) and disease substrate (urinary hexose tetrasaccharide \[Hex4\]). Blood samples will be collected for determination of total GAA protein levels and AT2221 concentrations in plasma for a population PK analysis. Safety assessments include monitoring of adverse events (AEs), including infusion associated reactions (IARs), clinical laboratory tests (chemistry, hematology, and urinalysis), vital signs, physical examinations including weight, electrocardiograms (ECGs), and immunogenicity. Concomitant medications and nondrug therapies will also be recorded.
Interventions
BIOLOGICALCipaglucosidase Alfa
Participants received an intravenous (IV) infusion dose over a 4-hour duration every 2 weeks (Q2W).
DRUGMiglustat
Participants received weight-based doses 1 hour prior to cipaglucosidase alfa infusion Q2W.
BIOLOGICALAlglucosidase Alfa
Participants received an IV infusion dose over a 4-hour duration Q2W.
DRUGPlacebo
Miglustat matching placebo was administered orally 1 hour prior to alglucosidase alfa infusion Q2W.
Sponsors
Amicus Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject must provide signed informed consent prior to any study-related procedures being performed. 2. Male and female subjects are ≥ 18 years old and weigh ≥ 40 kg at screening. 3. Female subjects of childbearing potential and male subjects must agree to use medically accepted methods of contraception during the study and for 90 days after the last dose of study drug. 4. Subject must have a diagnosis of LOPD based on documentation of one of the following: 1. deficiency of GAA enzyme 2. GAA genotyping 5. Subject is classified as one of the following with respect to ERT status: 1. ERT-experienced, defined as currently receiving standard of care ERT (alglucosidase alfa) at the recommended dose and regimen (ie, 20 mg/kg dose every 2 weeks) for ≥ 24 months 2. ERT-naïve, defined as never having received investigational or commercially available ERT 6. Subject has a sitting FVC ≥ 30% of the predicted value for healthy adults (National Health and Nutrition Examination Survey III) at screening. 7. Subject performs two 6MWTs at screening that are valid, as determined by the clinical evaluator, and that meet all of the following criteria: 1. both screening values of 6MWD are ≥ 75 meters 2. both screening values of 6MWD are ≤ 90% of the predicted value for healthy adults 3. the lower value of 6MWD is within 20% of the higher value of 6MWD
Exclusion criteria
1. Subject has received any investigational therapy or pharmacological treatment for Pompe disease, other than alglucosidase alfa, within 30 days or 5 half-lives of the therapy or treatment, whichever is longer, before Day 1 or is anticipated to do so during the study. 2. Subject has received gene therapy for Pompe disease 3. Subject is taking any of the following prohibited medications within 30 days before Day 1: * miglitol (eg, Glyset) * miglustat (eg, Zavesca) * acarbose (eg, Precose or Glucobay) * voglibose (eg, Volix, Vocarb, or Volibo) Note: None of these medications have a half-life that, when multiplied by 5, is longer than 30 days. 4. Subject requires the use of invasive or noninvasive ventilation support for \> 6 hours per day while awake. 5. Subject has a hypersensitivity to any of the excipients in ATB200, alglucosidase alfa, or AT2221. 6. Subject has a medical condition or any other extenuating circumstance that may, in the opinion of the investigator or medical monitor, pose an undue safety risk to the subject or may compromise his/her ability to comply with or adversely impact protocol requirements. This includes clinical depression (as diagnosed by a psychiatrist or other mental health professional) with uncontrolled or poorly controlled symptoms. 7. Subject, if female, is pregnant or breastfeeding at screening. 8. Subject, whether male or female, is planning to conceive a child during the study. 9. Subject does not have documentation of diagnosis of Pompe disease and refuses to undergo genetic testing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 52 in 6 Minute Walk Distance (6MWD) | Baseline, Week 52 | The efficacy of cipaglucosidase alfa/miglustat co-administration on ambulatory function was measured by the 6MWT. The 6MWD, measured in meters, is the distance walked on the 6MWT. A greater distance indicated greater endurance. An increase from baseline indicated improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 52 in the Manual Muscle Test (MMT) Score for the Lower Extremities | Baseline, Week 52 | The total score for the MMT lower extremity strength included the following 8 body parts: right/left hip flexion, right/left hip abduction, right/left knee flexion and right/left knee extension. The MMT lower extremity score ranged from 0 to 40, with lower scores indicating weaker muscle strength. An increase from baseline indicated increased muscle strength. |
| Change From Baseline to Week 26 in 6MWD | Baseline, Week 26 | The 6MWD, measured in meters, is the distance walked on the 6MWT. |
| Change From Baseline to Week 52 in the Total Score for the Patient- Reported Outcomes Measurement Information System (PROMIS®) - Physical Function | Baseline, Week 52 | Physical Function Short Form 20a (v2.0) consisted of 20 questions. The first 14 questions were each scored on a scale from 1 to 5 as follows: 1 = unable to do; 2 = with much difficulty; 3 = with some difficulty; 4 = with a little difficulty; 5 = without any difficulty; the next 6 questions were each scored on a scale from 1 to 5 as follows: 1 = cannot do; 2 = quite a lot; 3 = somewhat; 4 = very little; 5 = not at all. The total score was calculated by summing up scores (1 to 5) across all items. Total scores range from 20 to 100. A higher score represented a better outcome. |
| Change From Baseline to Week 52 in the Total Score for the PROMIS® - Fatigue | Baseline, Week 52 | Fatigue Short Form 8a consisted of 6 questions, each scored on a scale from 1 to 5 as follows: 1 = not at all; 2 = a little bit; 3 = somewhat; 4 = quite a bit; 5 = very much; and 2 questions, each scored on a scale from 1 to 5 as follows: 1 = never; 2 = rarely; 3 = sometimes; 4 = often; 5 = always. The total score was calculated by summing up scores (1 to 5) across all items. A lower score represented lower fatigue symptoms. |
| Change From Baseline to Week 52 in the Total Score for the Gait, Stairs, Gowers' Maneuver, and Chair (GSGC) | Baseline, Week 52 | The GSGC consisted of a 10-meter walk for evaluation of gait, a 4-stair climb, Gowers' maneuver, and arising from a chair. Results of the GSGC included the time required to complete the individual tests, individual scores for each of the tests (1 to 7 points for each of gait, 4-stair climb, and Gowers' maneuver, and 1 to 6 points for arising from a chair), and a total score. GSGC total score was the sum of the component scores from the 4 functional tests. The total score ranged from a minimum of 4 points (normal performance) to a maximum of 27 points (worst performance). |
| Change From Baseline to Week 52 in Rasch-Built Pompe-Specific Activity (R-PAct) Total Score | Baseline, Week 52 | The R-PAct scale was an 18-item questionnaire to measure limitations in activities and restriction in social participation. Possible responses to questions were as follows: unable to perform, able to perform, but with difficulty, and able to perform without difficulty. The total score was calculated by summing up the observed scores across the 18 items and it ranged from 0 to 36, with higher values representing lower level of disease impact on the muscles. |
| Change From Baseline to Week 52 in European Quality of Life-5 Dimensions 5 Response Levels (EQ-5D-5L) Based on the EuroQol Visual Analogue Scale (EQ VAS) Quantitative Score | Baseline, Week 52 | The EuroQol Visual Analogue Scale (EQ VAS) is a vertical visual analogue scale that records the respondent's own assessment of his or her overall health status at the time of completion. Scores range from 0 (the worst health you can imagine) to 100 (the best health you can imagine). Higher EQ VAS scores represent an improved sense of overall health while lower scores represent a worsening of overall health. |
| Change From Baseline to Week 52 in Sitting Slow Vital Capacity (SVC) % Predicted | Baseline, Week 52 | SVC is a standard pulmonary function test used to quantify respiratory muscle weakness. |
| Change From Baseline to Week 52 in Maximal Inspiratory Pressure (MIP) % Predicted | Baseline, Week 52 | The percent predicted values of MIP were calculated as: % predicted = (actual result / predicted result)\* 100, where the predicted results were obtained using the reference equations from Uldry and Fitting (1995). |
| Change From Baseline to Week 52 in Maximal Expiratory Pressure (MEP) % Predicted | Baseline, Week 52 | The percent predicted values of MEP were calculated as: % predicted = (actual result / predicted result) \* 100, where the predicted results were obtained using the reference equations from Uldry and Fitting (1995). |
| Change From Baseline to Week 52 in Sniff Nasal Inspiratory Pressure (SNIP) % Predicted | Baseline, Week 52 | The percent predicted values of SNIP were calculated as: % predicted = (actual result / predicted result) \* 100, where the predicted results were obtained using the reference equations from Evans and Whitelaw (2009). |
| Change From Baseline to Week 52 in % Predicted 6MWD | Baseline, Week 52 | The % predicted 6MWD = (actual 6MWD / predicted 6MWD) \* 100. The predicted values were calculated using Enright And Sherrill 1998 Reference Equations. |
| Change From Baseline to Week 52 in the Quantitative Muscle Test (QMT) Values | Baseline, Week 52 | QMT was measured using the hand-held dynamometer. Larger values (in kg) indicated greater muscle strength. |
| Change From Baseline to Week 52 in Other MMT Scores | Baseline, Week 52 | Each manual muscle test was evaluated on a scoring scale from 0 to 5, as follows: 0 = no muscle movement; 1 = visible muscle movement, but no movement at the joint; 2 = movement at the joint, but not against gravity; 3 = movement against gravity, but not against added resistance; 4 = movement against resistance, but less than normal; 5 = normal strength. Upper extremity score was the sum of scores for right/left shoulder abduction, right/left shoulder adduction, right/left elbow extension, and right/left elbow flexion, with the total score ranging from 0 to 40. Proximal muscle group score, the sum of scores for right/left hip flexion, right/left hip abduction, right/left shoulder abduction, and right/left shoulder adduction, with the total score ranging from 0 to 40. MMT total score was the sum of the lower and upper extremity scores and ranged from 0 to 80. Lower scores indicated lower overall muscle strength. An increase from baseline indicated improvement in muscle strength. |
| Change From Baseline to Week 52 in Maximum Vital Capacity (Maximum VC) % Predicted | Baseline, Week 52 | Maximum VC is the greater of the two VC values (FVC or SVC). |
| Change From Baseline to Week 52 in Sitting Forced Vital Capacity (FVC; % Predicted) | Baseline, Week 52 | The efficacy of cipaglucosidase alfa/miglustat co-administration on pulmonary function was measured by sitting FVC (% predicted). FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. |
| Change From Baseline in the Time to Complete Individual GSGC Component Tests and Timed Up and Go (TUG) Test at Week 52 | Baseline, Week 52 | Motor function test assessed the time to complete individual GSGC component tests (10-meter walk, 4- stair climb, Gowers' maneuver, and arise from a chair) and the TUG test. The TUG test assessed the time a subject needed to rise from a chair, walk 3 meters, turn around, walk back to the chair, and sit down. |
| Physician's Global Impression of Change (PGIC) Overall Status at Week 52 | Week 52 | Physician's Global Impression of Change is based on a single item that is scored on a 7-point rating scale ranging from 1 very much worse to 7 very much improved. A tertiary response variable (improving, declining, stable) was defined as follows: Improving, which consisted of improved, moderately improved, and very much improved; Declining, which consisted of worse, moderately worse, and very much worse; and Stable, which equaled to no change. |
| Subject's Global Impression of Change (SGIC) at Week 52 | Week 52 | The SGIC is designed to record the participants' impression of their functional status since starting study drug using a 7-point scale ranging from 1 very much worse to 7 very much improved. A tertiary response variable (improving, declining, stable) was defined as follows: Improving, which consisted of improved, moderately improved, and very much improved; Declining, which consisted of worse, moderately worse, and very much worse; and Stable, which equaled to no change. |
| Number of Participants Improving on Both 6MWD and % Predicted FVC at Week 52 | Week 52 | A composite subject-level response of the 2 relevant clinical outcomes, 6MWD and FVC (% predicted), was assessed. Prespecified thresholds were used for assessment of improvement consistent with published minimal clinically important difference values for comparable instruments in similar disease. |
| Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) | Baseline up to Week 52 | Treatment-emergent ADAs were defined as participants who had seroconverted or boosted their preexisting ADA during the study period. |
| Change From Baseline to Week 52 in Urinary Hexose Tetrasaccharide (Hex4) Level | Baseline, Week 52 | Levels of urinary Hex4, a biomarker of disease substrate, were measured. The assay specifically targets Hex4, the glucose tetrasaccharide (Glc4), which is a biomarker of glycogen storage. |
| Change From Baseline to Week 52 in Serum Creatine Kinase (CK) Level | Baseline, Week 52 | Change from baseline to Week 52 in serum CK level. CK levels were measured as part of the serum chemistry panel. |
| Population Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Experienced Participants Using Plasma Total GAA Protein Level by Signature Peptide Assay and Plasma Miglustat Concentration | Days 1 and 364 (Week 52) | On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-experienced participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional. |
| Population PK: Area Under the Concentration-Time Curve (AUC) of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Experienced Participants Using Plasma Total GAA Protein Level by Signature Peptide Assay and Plasma Miglustat Concentration | Days 1 and 364 (Week 52) | On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-experienced participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional. |
| Population PK: Cmax of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Participants | Days 1 and 364 (Week 52) | On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-naïve participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional. |
| Population PK: AUC of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Subjects | Days 1 and 364 (Week 52) | On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-naïve participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional. |
| Noncompartmental Analysis: Cmax of Plasma Total GAA Protein by Signature Peptide T09 in ERT-Naïve Subjects | Day 1 | A noncompartmental analysis was performed on ERT-naïve subjects, who underwent serial PK sampling during the study. On Day 1, serial blood samples were collected for ERT-naïve participants just prior to initiation of cipaglucosidase alfa/alglucosidase alfa infusion (time 0) and at 1, 2, 3, 3.5, 4, 4.5, 6, 8, 10, and 24 hours after the start of cipaglucosidase alfa/alglucosidase alfa infusion for plasma total human acid α-glucosidase (GAA) protein signature peptide T09 and plasma miglustat determinations. |
| Noncompartmental Analysis: AUC From Time 0 (Predose) to the Time of Last Quantifiable Concentration of Plasma Total GAA Protein by Signature Peptide T09 in ERT-Naïve Subjects | Day 1 | A noncompartmental analysis was performed on ERT-naïve subjects, who underwent serial PK sampling during the study. On Day 1, serial blood samples were collected for ERT-naïve participants just prior to initiation of cipaglucosidase alfa/alglucosidase alfa infusion (time 0) and at 1, 2, 3, 3.5, 4, 4.5, 6, 8, 10, and 24 hours after the start of cipaglucosidase alfa/alglucosidase alfa infusion for plasma total GAA protein signature peptide T09 and plasma miglustat determinations. |
| Comparison of Cmax of Cipaglucosidase Alfa in ERT-Experienced and ERT-Naïve Populations | Days 1 and 364 (Week 52) | On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional. |
| Comparison of AUC of Cipaglucosidase Alfa in ERT- Experienced and ERT-Naïve Populations | Days 1 and 364 (Week 52) | On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional. |
| Change From Baseline to Week 52 in PROMIS-Dyspnea and Upper Extremities Total Scores | Baseline, Week 52 | The Upper Extremities Short Form 7a consisted of 7 items each scored on a decreasing scale from 1 to 5 as follows: 1 = unable to do; 2 = with much difficulty; 3 = with some difficulty; 4 = with a little difficulty; 5 = without any difficulty. Dyspnea Severity Short Form 10a consisted of 10 items each scored on a scale from 0 to 3 as follows: 0 = no shortness of breath; 1 = mildly short of breath; 2 = moderately short of breath; 3 = severely short of breath. A total score was generated for each instrument by adding up each item. Total scores for upper extremities range from 7 to 35. Total scores for dyspnea range from 0 to 30. A higher score for upper extremities represented improvement in symptoms. A lower score for dyspnea severity represented improvement in symptoms. |
Countries
Argentina, Australia, Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Canada, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Netherlands, New Zealand, Poland, Slovenia, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States
Participant flow
Pre-assignment details
A total of 125 participants were randomized in the study at 62 clinical sites across 24 countries; 123 participants received at least 1 dose of study drug. Two participants randomized to the alglucosidase alfa/placebo group were never dosed because genotyping did not confirm the diagnosis of Pompe disease.
Participants by arm
| Arm | Count |
|---|---|
| Cipaglucosidase Alfa/Miglustat Cipaglucosidase alfa co-administered with miglustat Q2W. | 85 |
| Alglucosidase Alfa/Placebo Alglucosidase alfa co-administered with placebo Q2W. | 38 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | COVID-19 Pandemic | 1 | 0 |
| Overall Study | Discontinued due to COVID-19 related pneumonia | 1 | 0 |
| Overall Study | Genotyping did not confirm diagnosis of Pompe disease | 0 | 2 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Cipaglucosidase Alfa/Miglustat | Alglucosidase Alfa/Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 3 Participants | 14 Participants |
| Age, Categorical Between 18 and 65 years | 74 Participants | 35 Participants | 109 Participants |
| Age, Continuous | 47.6 years STANDARD_DEVIATION 13.25 | 45.1 years STANDARD_DEVIATION 13.3 | 46.8 years STANDARD_DEVIATION 13.27 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) White | 74 Participants | 30 Participants | 104 Participants |
| Sex: Female, Male Female | 49 Participants | 18 Participants | 67 Participants |
| Sex: Female, Male Male | 36 Participants | 20 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 85 | 0 / 38 |
| other Total, other adverse events | 69 / 85 | 32 / 38 |
| serious Total, serious adverse events | 8 / 85 | 1 / 38 |
Outcome results
Primary
Change From Baseline to Week 52 in 6 Minute Walk Distance (6MWD)
The efficacy of cipaglucosidase alfa/miglustat co-administration on ambulatory function was measured by the 6MWT. The 6MWD, measured in meters, is the distance walked on the 6MWT. A greater distance indicated greater endurance. An increase from baseline indicated improvement.
Time frame: Baseline, Week 52
Population: Analysis was performed on Intent-to-treat (ITT)-observed (OBS) population. Number of participants analyzed are based on those who had 6MWD result at Week 52. In addition, 1 outlier subject in the alglucosidase alfa/placebo group was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in 6 Minute Walk Distance (6MWD) | 21.31 meter | Standard Error 11.56 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in 6 Minute Walk Distance (6MWD) | 7.10 meter | Standard Error 7.043 |
Comparison: The primary and key secondary endpoints were tested in hierarchical order as follows:~The test for the primary endpoint was conducted first at the 1-sided 0.025 significance level, and if significant, the ordered key secondary endpoints were similarly tested. If at any point the null hypothesis for superiority failed to be rejected, then that comparison and any other comparison below it could not be claimed as successful and would be considered nominal.p-value: 0.04895% CI: [-2.6, 31.02]MMRM
Secondary
Change From Baseline in the Time to Complete Individual GSGC Component Tests and Timed Up and Go (TUG) Test at Week 52
Motor function test assessed the time to complete individual GSGC component tests (10-meter walk, 4- stair climb, Gowers' maneuver, and arise from a chair) and the TUG test. The TUG test assessed the time a subject needed to rise from a chair, walk 3 meters, turn around, walk back to the chair, and sit down.
Time frame: Baseline, Week 52
Population: Analyses were performed on ITT-LOCF population. Number of participants analyzed for each of the GSGC components and the TUG test displayed are based upon the number of participants who had both baseline and post-baseline values for each respective GSGC component and the TUG test. In addition, the outlier subject in the alglucosidase alfa/placebo group was not included in the analyses.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline in the Time to Complete Individual GSGC Component Tests and Timed Up and Go (TUG) Test at Week 52 | Time to complete the 4-stair climb | -6.75 seconds | Standard Error 0.851 |
| Cipaglucosidase Alfa/Miglustat | Change From Baseline in the Time to Complete Individual GSGC Component Tests and Timed Up and Go (TUG) Test at Week 52 | Time to arise from a chair | -7.57 seconds | Standard Error 0.409 |
| Cipaglucosidase Alfa/Miglustat | Change From Baseline in the Time to Complete Individual GSGC Component Tests and Timed Up and Go (TUG) Test at Week 52 | Time to complete the Gowers' maneuver | -0.36 seconds | Standard Error 0.799 |
| Cipaglucosidase Alfa/Miglustat | Change From Baseline in the Time to Complete Individual GSGC Component Tests and Timed Up and Go (TUG) Test at Week 52 | Time to complete the timed up and go test | -0.39 seconds | Standard Error 0.768 |
| Cipaglucosidase Alfa/Miglustat | Change From Baseline in the Time to Complete Individual GSGC Component Tests and Timed Up and Go (TUG) Test at Week 52 | Time to complete the 10-meter walk | -0.60 seconds | Standard Error 0.631 |
| Alglucosidase Alfa/Placebo | Change From Baseline in the Time to Complete Individual GSGC Component Tests and Timed Up and Go (TUG) Test at Week 52 | Time to complete the timed up and go test | 0.09 seconds | Standard Error 1.217 |
| Alglucosidase Alfa/Placebo | Change From Baseline in the Time to Complete Individual GSGC Component Tests and Timed Up and Go (TUG) Test at Week 52 | Time to complete the 10-meter walk | 2.06 seconds | Standard Error 0.967 |
| Alglucosidase Alfa/Placebo | Change From Baseline in the Time to Complete Individual GSGC Component Tests and Timed Up and Go (TUG) Test at Week 52 | Time to complete the 4-stair climb | -3.61 seconds | Standard Error 1.308 |
| Alglucosidase Alfa/Placebo | Change From Baseline in the Time to Complete Individual GSGC Component Tests and Timed Up and Go (TUG) Test at Week 52 | Time to complete the Gowers' maneuver | -1.95 seconds | Standard Error 1.281 |
| Alglucosidase Alfa/Placebo | Change From Baseline in the Time to Complete Individual GSGC Component Tests and Timed Up and Go (TUG) Test at Week 52 | Time to arise from a chair | -6.75 seconds | Standard Error 0.643 |
Secondary
Change From Baseline to Week 26 in 6MWD
The 6MWD, measured in meters, is the distance walked on the 6MWT.
Time frame: Baseline, Week 26
Population: Analysis was performed on ITT-LOCF population. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 26 in 6MWD | 16.45 meter | Standard Error 3.36 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 26 in 6MWD | 8.28 meter | Standard Error 5.168 |
Comparison: Change from baseline to Week 26 in 6MWD was the third of 6 key secondary efficacy endpoints, which were analyzed according to a hierarchical order.p-value: 0.09795% CI: [-4.24, 20.57]ANCOVA
Secondary
Change From Baseline to Week 52 in European Quality of Life-5 Dimensions 5 Response Levels (EQ-5D-5L) Based on the EuroQol Visual Analogue Scale (EQ VAS) Quantitative Score
The EuroQol Visual Analogue Scale (EQ VAS) is a vertical visual analogue scale that records the respondent's own assessment of his or her overall health status at the time of completion. Scores range from 0 (the worst health you can imagine) to 100 (the best health you can imagine). Higher EQ VAS scores represent an improved sense of overall health while lower scores represent a worsening of overall health.
Time frame: Baseline, Week 52
Population: Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had neither baseline nor post-baseline values, and was not included in the analysis. In the alglucosidase alfa/placebo group, 1 subject had neither baseline nor post-baseline values, and was not included in the analysis. In addition, the outlier subject was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in European Quality of Life-5 Dimensions 5 Response Levels (EQ-5D-5L) Based on the EuroQol Visual Analogue Scale (EQ VAS) Quantitative Score | 0.03 score on a scale | Standard Error 1.542 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in European Quality of Life-5 Dimensions 5 Response Levels (EQ-5D-5L) Based on the EuroQol Visual Analogue Scale (EQ VAS) Quantitative Score | 3.61 score on a scale | Standard Error 2.4 |
Secondary
Change From Baseline to Week 52 in Maximal Expiratory Pressure (MEP) % Predicted
The percent predicted values of MEP were calculated as: % predicted = (actual result / predicted result) \* 100, where the predicted results were obtained using the reference equations from Uldry and Fitting (1995).
Time frame: Baseline, Week 52
Population: Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had no post-baseline value and was not included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in Maximal Expiratory Pressure (MEP) % Predicted | 0.51 percentage of predicted MEP | Standard Error 1.996 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in Maximal Expiratory Pressure (MEP) % Predicted | -1.35 percentage of predicted MEP | Standard Error 3.052 |
Secondary
Change From Baseline to Week 52 in Maximal Inspiratory Pressure (MIP) % Predicted
The percent predicted values of MIP were calculated as: % predicted = (actual result / predicted result)\* 100, where the predicted results were obtained using the reference equations from Uldry and Fitting (1995).
Time frame: Baseline, Week 52
Population: Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had no post-baseline value and was not included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in Maximal Inspiratory Pressure (MIP) % Predicted | 1.89 percentage of predicted MIP | Standard Error 2.079 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in Maximal Inspiratory Pressure (MIP) % Predicted | -2.31 percentage of predicted MIP | Standard Error 3.178 |
Secondary
Change From Baseline to Week 52 in Maximum Vital Capacity (Maximum VC) % Predicted
Maximum VC is the greater of the two VC values (FVC or SVC).
Time frame: Baseline, Week 52
Population: Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had no post-baseline value and was not included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in Maximum Vital Capacity (Maximum VC) % Predicted | -1.286 percentage of predicted maximum VC | Standard Error 0.613 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in Maximum Vital Capacity (Maximum VC) % Predicted | -3.695 percentage of predicted maximum VC | Standard Error 0.936 |
Secondary
Change From Baseline to Week 52 in Other MMT Scores
Each manual muscle test was evaluated on a scoring scale from 0 to 5, as follows: 0 = no muscle movement; 1 = visible muscle movement, but no movement at the joint; 2 = movement at the joint, but not against gravity; 3 = movement against gravity, but not against added resistance; 4 = movement against resistance, but less than normal; 5 = normal strength. Upper extremity score was the sum of scores for right/left shoulder abduction, right/left shoulder adduction, right/left elbow extension, and right/left elbow flexion, with the total score ranging from 0 to 40. Proximal muscle group score, the sum of scores for right/left hip flexion, right/left hip abduction, right/left shoulder abduction, and right/left shoulder adduction, with the total score ranging from 0 to 40. MMT total score was the sum of the lower and upper extremity scores and ranged from 0 to 80. Lower scores indicated lower overall muscle strength. An increase from baseline indicated improvement in muscle strength.
Time frame: Baseline, Week 52
Population: Analyses were performed on ITT-LOCF population. Number of participants analyzed for each of the MMT parameters displayed are based upon the number of participants who had both baseline and post-baseline values for each respective MMT parameter. In addition, the outlier subject in the alglucosidase alfa/placebo group was not included in the analyses.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in Other MMT Scores | MMT Upper Extremity Score | 1.54 score on a scale | Standard Error 0.323 |
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in Other MMT Scores | MMT Total Score | 3.24 score on a scale | Standard Error 0.622 |
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in Other MMT Scores | MMT Proximal Muscle Group Score | 1.82 score on a scale | Standard Error 0.393 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in Other MMT Scores | MMT Upper Extremity Score | 0.60 score on a scale | Standard Error 0.491 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in Other MMT Scores | MMT Total Score | 1.02 score on a scale | Standard Error 0.966 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in Other MMT Scores | MMT Proximal Muscle Group Score | 0.70 score on a scale | Standard Error 0.599 |
Secondary
Change From Baseline to Week 52 in % Predicted 6MWD
The % predicted 6MWD = (actual 6MWD / predicted 6MWD) \* 100. The predicted values were calculated using Enright And Sherrill 1998 Reference Equations.
Time frame: Baseline, Week 52
Population: Analysis was performed on ITT-LOCF population. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in % Predicted 6MWD | 4.039 percentage of predicted 6MWD | Standard Error 0.716 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in % Predicted 6MWD | 1.655 percentage of predicted 6MWD | Standard Error 1.102 |
Secondary
Change From Baseline to Week 52 in PROMIS-Dyspnea and Upper Extremities Total Scores
The Upper Extremities Short Form 7a consisted of 7 items each scored on a decreasing scale from 1 to 5 as follows: 1 = unable to do; 2 = with much difficulty; 3 = with some difficulty; 4 = with a little difficulty; 5 = without any difficulty. Dyspnea Severity Short Form 10a consisted of 10 items each scored on a scale from 0 to 3 as follows: 0 = no shortness of breath; 1 = mildly short of breath; 2 = moderately short of breath; 3 = severely short of breath. A total score was generated for each instrument by adding up each item. Total scores for upper extremities range from 7 to 35. Total scores for dyspnea range from 0 to 30. A higher score for upper extremities represented improvement in symptoms. A lower score for dyspnea severity represented improvement in symptoms.
Time frame: Baseline, Week 52
Population: Analyses were performed on ITT-LOCF population. Number of participants analyzed for each of the PROMIS total scores displayed are based upon the number of participants who had both baseline and post-baseline values for each respective PROMIS total score (PROMIS-Dyspnea and Upper Extremities Total Scores). In addition, the outlier subject in the alglucosidase alfa/placebo group was not included in the analyses.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in PROMIS-Dyspnea and Upper Extremities Total Scores | PROMIS-Dyspnea Total Score | -0.41 score on a scale | Standard Error 0.426 |
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in PROMIS-Dyspnea and Upper Extremities Total Scores | PROMIS-Upper Extremities Total Score | 0.97 score on a scale | Standard Error 0.545 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in PROMIS-Dyspnea and Upper Extremities Total Scores | PROMIS-Dyspnea Total Score | -1.50 score on a scale | Standard Error 0.652 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in PROMIS-Dyspnea and Upper Extremities Total Scores | PROMIS-Upper Extremities Total Score | 0.87 score on a scale | Standard Error 0.833 |
Secondary
Change From Baseline to Week 52 in Rasch-Built Pompe-Specific Activity (R-PAct) Total Score
The R-PAct scale was an 18-item questionnaire to measure limitations in activities and restriction in social participation. Possible responses to questions were as follows: unable to perform, able to perform, but with difficulty, and able to perform without difficulty. The total score was calculated by summing up the observed scores across the 18 items and it ranged from 0 to 36, with higher values representing lower level of disease impact on the muscles.
Time frame: Baseline, Week 52
Population: Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 16 subjects had neither baseline nor post-baseline values, and were not included in the analysis. In the alglucosidase alfa/placebo group, 4 subjects had neither baseline nor post-baseline values, and were not included in the analysis. In addition, the outlier subject was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in Rasch-Built Pompe-Specific Activity (R-PAct) Total Score | 0.04 score on a scale | Standard Error 0.387 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in Rasch-Built Pompe-Specific Activity (R-PAct) Total Score | 0.51 score on a scale | Standard Error 0.567 |
Secondary
Change From Baseline to Week 52 in Serum Creatine Kinase (CK) Level
Change from baseline to Week 52 in serum CK level. CK levels were measured as part of the serum chemistry panel.
Time frame: Baseline, Week 52
Population: Analysis was performed on ITT-LOCF population. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in Serum Creatine Kinase (CK) Level | -130.5 U/L | Standard Deviation 231.18 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in Serum Creatine Kinase (CK) Level | 60.2 U/L | Standard Deviation 159.49 |
Secondary
Change From Baseline to Week 52 in Sitting Forced Vital Capacity (FVC; % Predicted)
The efficacy of cipaglucosidase alfa/miglustat co-administration on pulmonary function was measured by sitting FVC (% predicted). FVC is a standard pulmonary function test used to quantify respiratory muscle weakness.
Time frame: Baseline, Week 52
Population: Analysis was performed on ITT-Last Observation Carried Forward (LOCF) population. In the cipaglucosidase alfa/miglustat group, 1 subject had no post-baseline values and was not included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in Sitting Forced Vital Capacity (FVC; % Predicted) | -1.04 percentage of predicted FVC | Standard Error 0.624 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in Sitting Forced Vital Capacity (FVC; % Predicted) | -3.70 percentage of predicted FVC | Standard Error 0.953 |
Comparison: Change from baseline to Week 52 in sitting FVC was the first of 6 key secondary efficacy endpoints, which were analyzed according to a hierarchical order.p-value: 0.01295% CI: [0.37, 4.95]ANCOVA
Secondary
Change From Baseline to Week 52 in Sitting Slow Vital Capacity (SVC) % Predicted
SVC is a standard pulmonary function test used to quantify respiratory muscle weakness.
Time frame: Baseline, Week 52
Population: Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 2 subjects had no post-baseline values and were not included in the analysis. In the alglucosidase alfa/placebo group, 1 subject had no baseline value, 1 subject had no post-baseline values, and they were not included in the analysis. In addition, the outlier subject was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in Sitting Slow Vital Capacity (SVC) % Predicted | -2.527 percentage of predicted SVC | Standard Error 0.977 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in Sitting Slow Vital Capacity (SVC) % Predicted | -5.368 percentage of predicted SVC | Standard Error 1.527 |
Secondary
Change From Baseline to Week 52 in Sniff Nasal Inspiratory Pressure (SNIP) % Predicted
The percent predicted values of SNIP were calculated as: % predicted = (actual result / predicted result) \* 100, where the predicted results were obtained using the reference equations from Evans and Whitelaw (2009).
Time frame: Baseline, Week 52
Population: Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had no post-baseline value and was not included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in Sniff Nasal Inspiratory Pressure (SNIP) % Predicted | 1.40 percentage of predicted SNIP | Standard Error 1.918 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in Sniff Nasal Inspiratory Pressure (SNIP) % Predicted | 4.53 percentage of predicted SNIP | Standard Error 2.929 |
Secondary
Change From Baseline to Week 52 in the Manual Muscle Test (MMT) Score for the Lower Extremities
The total score for the MMT lower extremity strength included the following 8 body parts: right/left hip flexion, right/left hip abduction, right/left knee flexion and right/left knee extension. The MMT lower extremity score ranged from 0 to 40, with lower scores indicating weaker muscle strength. An increase from baseline indicated increased muscle strength.
Time frame: Baseline, Week 52
Population: Analysis was performed on the ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had neither baseline nor post-baseline values and 4 subjects had no post-baseline values; these subjects were not included in the analysis. In the alglucosidase alfa/placebo group, 3 subjects had neither baseline nor post-baseline values, and were not included in the analysis. In addition, the outlier subject was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in the Manual Muscle Test (MMT) Score for the Lower Extremities | 1.64 score on a scale | Standard Error 0.388 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in the Manual Muscle Test (MMT) Score for the Lower Extremities | 0.68 score on a scale | Standard Error 0.603 |
Comparison: Change from baseline to Week 52 in the MMT score for the lower extremities was the second of 6 key secondary efficacy endpoints, which were analyzed according to a hierarchical order.p-value: 0.09595% CI: [-0.48, 2.4]ANCOVA
Secondary
Change From Baseline to Week 52 in the Quantitative Muscle Test (QMT) Values
QMT was measured using the hand-held dynamometer. Larger values (in kg) indicated greater muscle strength.
Time frame: Baseline, Week 52
Population: Analyses were performed on ITT-LOCF population. Number of participants analyzed for each of the QMT parameters displayed are based upon the number of participants who had both baseline and post-baseline values for each respective QMT parameter. In addition, the outlier subject in the alglucosidase alfa/placebo group was not included in the analyses.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in the Quantitative Muscle Test (QMT) Values | QMT Value for the Upper Extremities | 1.839 kilogram | Standard Error 2.098 |
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in the Quantitative Muscle Test (QMT) Values | QMT Total Value | 8.195 kilogram | Standard Error 5.079 |
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in the Quantitative Muscle Test (QMT) Values | QMT Value for the Lower Extremities | 6.496 kilogram | Standard Error 3.185 |
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in the Quantitative Muscle Test (QMT) Values | QMT Value for the Proximal Muscle Group | 3.401 kilogram | Standard Error 2.92 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in the Quantitative Muscle Test (QMT) Values | QMT Value for the Lower Extremities | 5.265 kilogram | Standard Error 4.854 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in the Quantitative Muscle Test (QMT) Values | QMT Value for the Upper Extremities | -0.553 kilogram | Standard Error 3.195 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in the Quantitative Muscle Test (QMT) Values | QMT Value for the Proximal Muscle Group | 0.945 kilogram | Standard Error 4.477 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in the Quantitative Muscle Test (QMT) Values | QMT Total Value | 5.198 kilogram | Standard Error 7.746 |
Secondary
Change From Baseline to Week 52 in the Total Score for the Gait, Stairs, Gowers' Maneuver, and Chair (GSGC)
The GSGC consisted of a 10-meter walk for evaluation of gait, a 4-stair climb, Gowers' maneuver, and arising from a chair. Results of the GSGC included the time required to complete the individual tests, individual scores for each of the tests (1 to 7 points for each of gait, 4-stair climb, and Gowers' maneuver, and 1 to 6 points for arising from a chair), and a total score. GSGC total score was the sum of the component scores from the 4 functional tests. The total score ranged from a minimum of 4 points (normal performance) to a maximum of 27 points (worst performance).
Time frame: Baseline, Week 52
Population: Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 11 subjects had neither baseline nor post-baseline values, and 2 had no post-baseline values; these subjects were not included in the analysis. In the alglucosidase alfa/placebo group, 5 subjects had neither baseline nor post-baseline values, and 2 had no post-baseline values; these subjects were not included in the analysis. In addition, the outlier subject was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in the Total Score for the Gait, Stairs, Gowers' Maneuver, and Chair (GSGC) | -0.567 score on a scale | Standard Error 0.28 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in the Total Score for the Gait, Stairs, Gowers' Maneuver, and Chair (GSGC) | 0.847 score on a scale | Standard Error 0.44 |
Comparison: Change from baseline to Week 52 in the total score for the GSGC was the sixth of 6 key secondary efficacy endpoints, which were analyzed according to a hierarchical order.p-value: 0.00495% CI: [-2.463, -0.364]ANCOVA
Secondary
Change From Baseline to Week 52 in the Total Score for the Patient- Reported Outcomes Measurement Information System (PROMIS®) - Physical Function
Physical Function Short Form 20a (v2.0) consisted of 20 questions. The first 14 questions were each scored on a scale from 1 to 5 as follows: 1 = unable to do; 2 = with much difficulty; 3 = with some difficulty; 4 = with a little difficulty; 5 = without any difficulty; the next 6 questions were each scored on a scale from 1 to 5 as follows: 1 = cannot do; 2 = quite a lot; 3 = somewhat; 4 = very little; 5 = not at all. The total score was calculated by summing up scores (1 to 5) across all items. Total scores range from 20 to 100. A higher score represented a better outcome.
Time frame: Baseline, Week 52
Population: Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had neither baseline nor post-baseline values, and was not included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in the Total Score for the Patient- Reported Outcomes Measurement Information System (PROMIS®) - Physical Function | 1.98 score on a scale | Standard Error 0.921 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in the Total Score for the Patient- Reported Outcomes Measurement Information System (PROMIS®) - Physical Function | 0.11 score on a scale | Standard Error 1.406 |
Comparison: Change from baseline to Week 52 in the total score for the PROMIS® - Physical Function was the fourth of 6 key secondary efficacy endpoints, which were analyzed according to a hierarchical order.p-value: 0.13895% CI: [-1.51, 5.25]ANCOVA
Secondary
Change From Baseline to Week 52 in the Total Score for the PROMIS® - Fatigue
Fatigue Short Form 8a consisted of 6 questions, each scored on a scale from 1 to 5 as follows: 1 = not at all; 2 = a little bit; 3 = somewhat; 4 = quite a bit; 5 = very much; and 2 questions, each scored on a scale from 1 to 5 as follows: 1 = never; 2 = rarely; 3 = sometimes; 4 = often; 5 = always. The total score was calculated by summing up scores (1 to 5) across all items. A lower score represented lower fatigue symptoms.
Time frame: Baseline, Week 52
Population: Analysis was performed on ITT-LOCF population. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in the Total Score for the PROMIS® - Fatigue | -1.90 score on a scale | Standard Error 0.585 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in the Total Score for the PROMIS® - Fatigue | -1.94 score on a scale | Standard Error 0.901 |
Comparison: Change from baseline to Week 52 in the total score for the PROMIS® - Fatigue was the fifth of 6 key secondary efficacy endpoints, which were analyzed according to a hierarchical order.p-value: 0.51595% CI: [-2.12, 2.2]ANCOVA
Secondary
Change From Baseline to Week 52 in Urinary Hexose Tetrasaccharide (Hex4) Level
Levels of urinary Hex4, a biomarker of disease substrate, were measured. The assay specifically targets Hex4, the glucose tetrasaccharide (Glc4), which is a biomarker of glycogen storage.
Time frame: Baseline, Week 52
Population: Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject had no post-baseline value and was not included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Change From Baseline to Week 52 in Urinary Hexose Tetrasaccharide (Hex4) Level | -1.88 mmol/mol creatinine | Standard Deviation 2.38 |
| Alglucosidase Alfa/Placebo | Change From Baseline to Week 52 in Urinary Hexose Tetrasaccharide (Hex4) Level | 1.22 mmol/mol creatinine | Standard Deviation 4.432 |
Secondary
Comparison of AUC of Cipaglucosidase Alfa in ERT- Experienced and ERT-Naïve Populations
On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.
Time frame: Days 1 and 364 (Week 52)
Population: Number analyzed based upon number of subjects with evaluable data for population PK analysis at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Comparison of AUC of Cipaglucosidase Alfa in ERT- Experienced and ERT-Naïve Populations | Day 1 | 1395 μg·h/mL | Geometric Coefficient of Variation 21.5 |
| Cipaglucosidase Alfa/Miglustat | Comparison of AUC of Cipaglucosidase Alfa in ERT- Experienced and ERT-Naïve Populations | Day 364 | 1476 μg·h/mL | Geometric Coefficient of Variation 21.8 |
| Alglucosidase Alfa/Placebo | Comparison of AUC of Cipaglucosidase Alfa in ERT- Experienced and ERT-Naïve Populations | Day 1 | 1343 μg·h/mL | Geometric Coefficient of Variation 25.7 |
| Alglucosidase Alfa/Placebo | Comparison of AUC of Cipaglucosidase Alfa in ERT- Experienced and ERT-Naïve Populations | Day 364 | 1457 μg·h/mL | Geometric Coefficient of Variation 19.2 |
Secondary
Comparison of Cmax of Cipaglucosidase Alfa in ERT-Experienced and ERT-Naïve Populations
On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.
Time frame: Days 1 and 364 (Week 52)
Population: Number analyzed based upon number of subjects with evaluable data for population PK analysis at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Comparison of Cmax of Cipaglucosidase Alfa in ERT-Experienced and ERT-Naïve Populations | Day 1 | 280 μg/mL | Geometric Coefficient of Variation 18.5 |
| Cipaglucosidase Alfa/Miglustat | Comparison of Cmax of Cipaglucosidase Alfa in ERT-Experienced and ERT-Naïve Populations | Day 364 | 296 μg/mL | Geometric Coefficient of Variation 19.9 |
| Alglucosidase Alfa/Placebo | Comparison of Cmax of Cipaglucosidase Alfa in ERT-Experienced and ERT-Naïve Populations | Day 1 | 273 μg/mL | Geometric Coefficient of Variation 18.1 |
| Alglucosidase Alfa/Placebo | Comparison of Cmax of Cipaglucosidase Alfa in ERT-Experienced and ERT-Naïve Populations | Day 364 | 290 μg/mL | Geometric Coefficient of Variation 17.4 |
Secondary
Noncompartmental Analysis: AUC From Time 0 (Predose) to the Time of Last Quantifiable Concentration of Plasma Total GAA Protein by Signature Peptide T09 in ERT-Naïve Subjects
A noncompartmental analysis was performed on ERT-naïve subjects, who underwent serial PK sampling during the study. On Day 1, serial blood samples were collected for ERT-naïve participants just prior to initiation of cipaglucosidase alfa/alglucosidase alfa infusion (time 0) and at 1, 2, 3, 3.5, 4, 4.5, 6, 8, 10, and 24 hours after the start of cipaglucosidase alfa/alglucosidase alfa infusion for plasma total GAA protein signature peptide T09 and plasma miglustat determinations.
Time frame: Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Noncompartmental Analysis: AUC From Time 0 (Predose) to the Time of Last Quantifiable Concentration of Plasma Total GAA Protein by Signature Peptide T09 in ERT-Naïve Subjects | 1264 μg·h/mL | Geometric Coefficient of Variation 28.9 |
| Alglucosidase Alfa/Placebo | Noncompartmental Analysis: AUC From Time 0 (Predose) to the Time of Last Quantifiable Concentration of Plasma Total GAA Protein by Signature Peptide T09 in ERT-Naïve Subjects | 1656 μg·h/mL | Geometric Coefficient of Variation 28.9 |
| Miglustat | Noncompartmental Analysis: AUC From Time 0 (Predose) to the Time of Last Quantifiable Concentration of Plasma Total GAA Protein by Signature Peptide T09 in ERT-Naïve Subjects | 20588 μg·h/mL | Geometric Coefficient of Variation 36.8 |
Secondary
Noncompartmental Analysis: Cmax of Plasma Total GAA Protein by Signature Peptide T09 in ERT-Naïve Subjects
A noncompartmental analysis was performed on ERT-naïve subjects, who underwent serial PK sampling during the study. On Day 1, serial blood samples were collected for ERT-naïve participants just prior to initiation of cipaglucosidase alfa/alglucosidase alfa infusion (time 0) and at 1, 2, 3, 3.5, 4, 4.5, 6, 8, 10, and 24 hours after the start of cipaglucosidase alfa/alglucosidase alfa infusion for plasma total human acid α-glucosidase (GAA) protein signature peptide T09 and plasma miglustat determinations.
Time frame: Day 1
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Noncompartmental Analysis: Cmax of Plasma Total GAA Protein by Signature Peptide T09 in ERT-Naïve Subjects | 260 μg/mL | Geometric Coefficient of Variation 18.4 |
| Alglucosidase Alfa/Placebo | Noncompartmental Analysis: Cmax of Plasma Total GAA Protein by Signature Peptide T09 in ERT-Naïve Subjects | 364 μg/mL | Geometric Coefficient of Variation 66.7 |
| Miglustat | Noncompartmental Analysis: Cmax of Plasma Total GAA Protein by Signature Peptide T09 in ERT-Naïve Subjects | 2768 μg/mL | Geometric Coefficient of Variation 30.8 |
Secondary
Number of Participants Improving on Both 6MWD and % Predicted FVC at Week 52
A composite subject-level response of the 2 relevant clinical outcomes, 6MWD and FVC (% predicted), was assessed. Prespecified thresholds were used for assessment of improvement consistent with published minimal clinically important difference values for comparable instruments in similar disease.
Time frame: Week 52
Population: Analysis was performed on ITT-LOCF population. In the cipaglucosidase alfa/miglustat group, 1 subject who had no post-baseline FVC value was counted as not improved and included in the analysis. In the alglucosidase alfa/placebo group, the outlier subject was not included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Number of Participants Improving on Both 6MWD and % Predicted FVC at Week 52 | 14 Participants |
| Alglucosidase Alfa/Placebo | Number of Participants Improving on Both 6MWD and % Predicted FVC at Week 52 | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs)
Treatment-emergent ADAs were defined as participants who had seroconverted or boosted their preexisting ADA during the study period.
Time frame: Baseline up to Week 52
Population: Analysis was performed on safety population which included subjects who had received at least 1 dose of study drug. Number analyzed equals participants evaluable at specified treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) | ERT-naïve: Treatment-emergent ADAs | 19 participants |
| Cipaglucosidase Alfa/Miglustat | Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) | ERT-experienced: Treatment-emergent ADAs | 31 participants |
| Alglucosidase Alfa/Placebo | Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) | ERT-naïve: Treatment-emergent ADAs | 8 participants |
| Alglucosidase Alfa/Placebo | Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs) | ERT-experienced: Treatment-emergent ADAs | 5 participants |
Secondary
Physician's Global Impression of Change (PGIC) Overall Status at Week 52
Physician's Global Impression of Change is based on a single item that is scored on a 7-point rating scale ranging from 1 very much worse to 7 very much improved. A tertiary response variable (improving, declining, stable) was defined as follows: Improving, which consisted of improved, moderately improved, and very much improved; Declining, which consisted of worse, moderately worse, and very much worse; and Stable, which equaled to no change.
Time frame: Week 52
Population: Analysis was performed on ITT-OBS population. Number of participants analyzed are based on those who had PGIC data at Week 52. In addition, the outlier subject in the alglucosidase alfa/placebo group was not included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Physician's Global Impression of Change (PGIC) Overall Status at Week 52 | Improving | 31 Participants |
| Cipaglucosidase Alfa/Miglustat | Physician's Global Impression of Change (PGIC) Overall Status at Week 52 | Stable | 38 Participants |
| Cipaglucosidase Alfa/Miglustat | Physician's Global Impression of Change (PGIC) Overall Status at Week 52 | Declining | 11 Participants |
| Alglucosidase Alfa/Placebo | Physician's Global Impression of Change (PGIC) Overall Status at Week 52 | Improving | 10 Participants |
| Alglucosidase Alfa/Placebo | Physician's Global Impression of Change (PGIC) Overall Status at Week 52 | Stable | 16 Participants |
| Alglucosidase Alfa/Placebo | Physician's Global Impression of Change (PGIC) Overall Status at Week 52 | Declining | 10 Participants |
Secondary
Population Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Experienced Participants Using Plasma Total GAA Protein Level by Signature Peptide Assay and Plasma Miglustat Concentration
On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-experienced participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.
Time frame: Days 1 and 364 (Week 52)
Population: Number analyzed equals participants evaluable at specified time points.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Population Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Experienced Participants Using Plasma Total GAA Protein Level by Signature Peptide Assay and Plasma Miglustat Concentration | Day 1 | 280 μg/mL | Geometric Coefficient of Variation 18.5 |
| Cipaglucosidase Alfa/Miglustat | Population Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Experienced Participants Using Plasma Total GAA Protein Level by Signature Peptide Assay and Plasma Miglustat Concentration | Day 364 | 293 μg/mL | Geometric Coefficient of Variation 19.9 |
| Alglucosidase Alfa/Placebo | Population Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Experienced Participants Using Plasma Total GAA Protein Level by Signature Peptide Assay and Plasma Miglustat Concentration | Day 1 | 289 μg/mL | Geometric Coefficient of Variation 13.2 |
| Alglucosidase Alfa/Placebo | Population Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Experienced Participants Using Plasma Total GAA Protein Level by Signature Peptide Assay and Plasma Miglustat Concentration | Day 364 | 283 μg/mL | Geometric Coefficient of Variation 17.6 |
Secondary
Population PK: Area Under the Concentration-Time Curve (AUC) of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Experienced Participants Using Plasma Total GAA Protein Level by Signature Peptide Assay and Plasma Miglustat Concentration
On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-experienced participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.
Time frame: Days 1 and 364 (Week 52)
Population: Number analyzed equals participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Population PK: Area Under the Concentration-Time Curve (AUC) of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Experienced Participants Using Plasma Total GAA Protein Level by Signature Peptide Assay and Plasma Miglustat Concentration | Day 1 | 1395 μg·h/mL | Geometric Coefficient of Variation 21.5 |
| Cipaglucosidase Alfa/Miglustat | Population PK: Area Under the Concentration-Time Curve (AUC) of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Experienced Participants Using Plasma Total GAA Protein Level by Signature Peptide Assay and Plasma Miglustat Concentration | Day 364 | 1476 μg·h/mL | Geometric Coefficient of Variation 21.8 |
| Alglucosidase Alfa/Placebo | Population PK: Area Under the Concentration-Time Curve (AUC) of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Experienced Participants Using Plasma Total GAA Protein Level by Signature Peptide Assay and Plasma Miglustat Concentration | Day 1 | 1700 μg·h/mL | Geometric Coefficient of Variation 17.6 |
| Alglucosidase Alfa/Placebo | Population PK: Area Under the Concentration-Time Curve (AUC) of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Experienced Participants Using Plasma Total GAA Protein Level by Signature Peptide Assay and Plasma Miglustat Concentration | Day 364 | 1688 μg·h/mL | Geometric Coefficient of Variation 23.9 |
Secondary
Population PK: AUC of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Subjects
On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-naïve participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.
Time frame: Days 1 and 364 (Week 52)
Population: Number analyzed equals participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Population PK: AUC of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Subjects | Day 364 | 1457 μg·h/mL | Geometric Coefficient of Variation 19.2 |
| Cipaglucosidase Alfa/Miglustat | Population PK: AUC of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Subjects | Day 1 | 1343 μg·h/mL | Geometric Coefficient of Variation 25.7 |
| Alglucosidase Alfa/Placebo | Population PK: AUC of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Subjects | Day 1 | 1859 μg·h/mL | Geometric Coefficient of Variation 22.4 |
| Alglucosidase Alfa/Placebo | Population PK: AUC of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Subjects | Day 364 | 1964 μg·h/mL | Geometric Coefficient of Variation 26.8 |
Secondary
Population PK: Cmax of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Participants
On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-naïve participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.
Time frame: Days 1 and 364 (Week 52)
Population: Number analyzed equals participants evaluable at specified timepoints.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Population PK: Cmax of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Participants | Day 1 | 273 μg/mL | Geometric Coefficient of Variation 18.1 |
| Cipaglucosidase Alfa/Miglustat | Population PK: Cmax of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Participants | Day 364 | 290 μg/mL | Geometric Coefficient of Variation 17.4 |
| Alglucosidase Alfa/Placebo | Population PK: Cmax of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Participants | Day 1 | 342 μg/mL | Geometric Coefficient of Variation 31 |
| Alglucosidase Alfa/Placebo | Population PK: Cmax of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Participants | Day 364 | 359 μg/mL | Geometric Coefficient of Variation 28.1 |
Secondary
Subject's Global Impression of Change (SGIC) at Week 52
The SGIC is designed to record the participants' impression of their functional status since starting study drug using a 7-point scale ranging from 1 very much worse to 7 very much improved. A tertiary response variable (improving, declining, stable) was defined as follows: Improving, which consisted of improved, moderately improved, and very much improved; Declining, which consisted of worse, moderately worse, and very much worse; and Stable, which equaled to no change.
Time frame: Week 52
Population: Analysis was performed on ITT-OBS population. Number of participants analyzed are based on those who had SGIC data at Week 52. In addition, the outlier subject in the alglucosidase alfa/placebo group was not included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cipaglucosidase Alfa/Miglustat | Subject's Global Impression of Change (SGIC) at Week 52 | Improving | 36 Participants |
| Cipaglucosidase Alfa/Miglustat | Subject's Global Impression of Change (SGIC) at Week 52 | Stable | 33 Participants |
| Cipaglucosidase Alfa/Miglustat | Subject's Global Impression of Change (SGIC) at Week 52 | Declining | 12 Participants |
| Alglucosidase Alfa/Placebo | Subject's Global Impression of Change (SGIC) at Week 52 | Improving | 13 Participants |
| Alglucosidase Alfa/Placebo | Subject's Global Impression of Change (SGIC) at Week 52 | Stable | 12 Participants |
| Alglucosidase Alfa/Placebo | Subject's Global Impression of Change (SGIC) at Week 52 | Declining | 11 Participants |