COMET: Study to Compare the Efficacy and Safety of Enzyme Replacement Therapies Avalglucosidase Alfa and Alglucosidase Alfa Administered Every Other Week in Patients With Late-onset Pompe Disease Who Have Not Been Previously Treated for Pompe Disease

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02782741
• Collaborator: (none)
• Enrollment: 100
• Locations: 69
• Arms: 2
• Anticipated Duration (Months): 77.9
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Primary Objective:

To determine the effect of avalglucosidase alfa treatment on respiratory muscle strength measured by percent (%) predicted forced vital capacity (FVC) in the upright position, as compared to alglucosidase alfa.

Secondary Objective:

To determine the safety and effect of avalglucosidase alfa treatment on functional endurance (6-minute walk test, inspiratory muscle strength (maximum inspiratory pressure), expiratory muscle strength (maximum expiratory pressure), lower extremity muscle strength (hand-held dynamometry), motor function (Quick Motor Function Test), and health-related quality of life (Short Form-12).

Condition or Disease	Intervention/Treatment	Phase
Glycogen Storage Disease Type II;Pompe's Disease	Drug: Avalglucosidase alfa (GZ402666); Drug: Alglucosidase alfa (GZ419829)	Phase 3

Detailed Description

The duration of the study per participant will be up to approximately 6 years that will consist of a 14-day screening period (may be extended up to 8 weeks in pre-specified situations), a 49-week blinded treatment period (except for the subgroup of pediatric patients aged 3 to less than (<) 18 years enrolling directly in the open-label long-term follow-up phase), a 240-week open-label treatment period, and a 4-week post-treatment observation period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Multicenter, Multinational, Double-blinded Study Comparing the Efficacy and Safety of Repeated Biweekly Infusions of Avalglucosidase Alfa (neoGAA, GZ402666) and Alglucosidase Alfa in Treatment naïve Patients With Late-onset Pompe Disease
• Actual Study Start Date: Nov 2, 2016
• Actual Primary Completion Date: Mar 19, 2020
• Anticipated Study Completion Date: May 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: avalglucosidase alfa (GZ402666) Administered intravenously every 2 weeks	Drug: Avalglucosidase alfa (GZ402666); Pharmaceutical form: powder for concentrate for solution for infusion Route of administration: intravenous
Active Comparator: alglucosidase alfa (GZ419829) Administered intravenously every 2 weeks	Drug: Alglucosidase alfa (GZ419829); Pharmaceutical form: powder for concentrate for solution for infusion Route of administration: intravenous; Other Names: Myozyme Lumizyme

Outcome Measures

Primary Outcome Measures

1. PAP: Change From Baseline in Percent Predicted Forced Vital Capacity in Upright Position at Week 49 [Baseline, Week 49]

   FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Least square (LS) mean and standard error (SE) were derived from mixed model for repeated measure (MMRM) model with baseline FVC (% predicted, as continuous), sex, age (in years at baseline), treatment group, visit, interaction term between treatment group and visit as fixed effects. Percent of predicted FVC = (actual FVC measurement)/(predicted value of FVC) * 100. After non-inferiority (NI) testing, a test for superiority of avalglucosidase alfa versus alglucosidase alfa was performed with an overall 2-sided 5% level of significance.

Secondary Outcome Measures

1. PAP: Change From Baseline in Total Distance Walked During Six-minute Walk Test (6MWT) at Week 49 [Baseline, Week 49]

   6MWT was a standardized test that measured the distance (in meters) covered by the participant by walking on a flat, hard surface in a period of a 6-minute walk. Mean distance walked gives an indication of functional endurance. The greater the distance (that a participant could walk in 6 minutes), the greater the endurance. LS mean and SE were derived from MMRM model with baseline FVC (% predicted) and baseline 6MWT (distance walked in meter), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

2. PAP: Change From Baseline in Percent Predicted Maximal Inspiratory Pressure (MIP) in Upright Position at Week 49 [Baseline, Week 49]

   MIP is a quick and non-invasive test to measure strength of inspiratory muscles, primarily diaphragm, and allows for assessment of ventilatory failure, restrictive lung disease and respiratory muscle strength. MIP refers to how much air pressure force an individual creates by inhaling through the mouth as hard as possible. LS mean and SE were derived from MMRM model for MIP % predicted adjusted for MIP % predicted at baseline, age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

3. PAP: Change From Baseline in Percent Predicted Maximal Expiratory Pressure (MEP) in Upright Position at Week 49 [Baseline, Week 49]

   MEP is a quick and non-invasive test to measure strength of expiratory muscles, primarily diaphragm, and allows for assessment of ventilatory failure, restrictive lung disease and respiratory muscle strength. MEP is the greater pressure generated during maximal expiration. LS mean and SE were derived from MMRM model for MEP % predicted adjusted for MEP % predicted at baseline, age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

4. PAP: Change From Baseline in Lower Extremity Muscle Strength at Week 49 as Assessed by Hand-held Dynamometry (HHD) [Baseline, Week 49]

   HHD: a portable method for strength quantitation. To complete a make test, participant exerted maximal force against dynamometer with gradual increase in force and completed isometric hold for 4-5 seconds. Muscle strengths were collected in Newton. Every muscle group (hip: flexion, extension, abduction; knee: flexion, extension and ankle dorsiflexion) were measured 2 times and highest value was reported. Summary score was sum of 12 measurements (2 measurements per muscle group) from 6 muscle groups on each side (left and right). An increase from Baseline was reflective of increased muscle strength, whereas a decrease from Baseline was reflective of decreased muscle strength. LS mean and SE were derived from MMRM model for HHD lower extremity muscle strength composite score adjusted for summary HHD lower extremity score at baseline, baseline FVC (% predicted), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

5. PAP: Change From Baseline in Quick Motor Function Test (QMFT) Total Scores at Week 49 [Baseline, Week 49]

   The QMFT was an observer administered test to evaluate changes in motor function. QMFT comprised of 16 items specifically difficult for participants with Pompe disease. Each item was scored separately on a 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), higher score represented better outcome. LS mean and SE were derived from MMRM models adjusted for total QMFT score at baseline, baseline FVC (% predicted), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

6. PAP: Change From Baseline in 12-item Short-form Health Survey (SF-12): Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 49 [Baseline, Week 49]

   SF-12, a 12 item-questionnaire, used to assess health-related quality of life in participants aged >=18 years at screening/baseline. SF-12 consisted of 12 items, which were categorized into eight domains (subscales) of functioning and well-being: physical functioning, role-physical, role emotional, mental health, bodily pain, general health, vitality and social functioning, with each domain score ranged from 0 (poor health) to 100 (better health), higher scores indicated good health condition. These eight domains were further summarized into 2 summary scores, PCS and MCS. The score range for each of these 2 summary scores was from 0 (poor health) to 100 (better health), higher scores indicated a better health-related quality of life. LS mean and SE were derived from MMRM models adjusted for baseline score (PCS or MCS), baseline FVC (% predicted), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

7. PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Infusion-associated Reactions (IARs) [From Baseline up to Week 49]

   AE: any untoward medical occurrence in participant who took study drug and not necessarily have to had causal relationship with treatment. TEAEs: AEs that developed/worsened in grade/became serious during TEAE period in PAP (from time of 1st treatment date to last treatment date+4 weeks for participants who didn't receive any treatment in open-label or to time just prior to 1st treatment in open-label for participants who received treatment in open-label). Protocol-defined IARs: AE of special interest (AESIs) that occurred during either infusion/observation period following infusion which were deemed to be related/possibly related to study drug. Algorithm-defined IARs: any TEAE meeting either 1 of 2 criteria: 1) event occurred from start to end of infusion + 24 hours, considered related to study drug, 2) If AE time component missed, compare AE start date with infusion start and end date. If AE start date was between infusion start and end date + 1 day and it was related to study drug.

8. Open-label Period: Number of Participants With Treatment-emergent Adverse Events and Infusion-associated Reactions [Week 50 to 145 in open-label long-term period]

   AE: any untoward medical occurrence in a participant who received study drug and did not necessarily have to had a causal relationship with treatment. TEAEs in open-label: AEs that developed/worsened in grade/became serious during TEAE period in open-label (from time of 1st open-label treatment to last treatment date + 4 weeks). Protocol-defined IARs: defined as AESIs that occurred during either infusion/observation period following infusion which were deemed to be related/possibly related to study drug. Algorithm-defined IARs: any TEAE meeting either 1 of 2 criteria: 1) event occurred from start to end of infusion plus 24 hours, considered related to study drug, 2) If AE time component missed, compare AE start date with infusion start and end date. If AE start date was between infusion start and end date plus 1 day and it was related to study drug.

9. PAP: Percentage of Participants With Treatment-emergent Antidrug Antibodies (ADA) Response [From Baseline up to Week 49]

   ADA response categories: 1) Treatment-induced: ADAs developed following administration of the study drug. If the baseline ADA sample was missing or non-reportable and at least one reportable on-treatment ADA sample was available, the baseline sample was considered as "negative". 2) Treatment-boosted: Pre-existing ADAs that were boosted at least two titer steps from baseline (i.e., 4 fold increase in titers) following administration of the study drug (any time after the first drug administration). 3) Treatment emergent: combination of treatment induced and treatment boosted.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 3 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria :

• The participant has confirmed acid alpha-glucosidase (GAA) enzyme deficiency from any tissue source and/or 2 confirmed GAA gene mutations.

• The participant must provide signed, informed consent prior to performing any study related procedures. Consent of a legally authorized guardian(s) is (are) required for legally minor participant as defined by local regulation. If the participant is legally minor, signed written consent shall be obtained from parent(s)/legal guardian and assent obtained from participants, if applicable.

Exclusion criteria:

• The participant is <3 years of age.

• The participant has known Pompe specific cardiac hypertrophy.

• The participant is wheelchair dependent.

• The participant is not able to ambulate 40 meters (approximately 130 feet) without stopping and without an assistive device.

• The participant requires invasive-ventilation (non-invasive ventilation is allowed).

• The participant is not able to successfully perform repeated forced vital capacity (FVC) measurements in upright position of greater than or equal to 30% predicted and less than or equal to 85% predicted.

• The participant (and participant's legal guardian if participant is legally minor as defined by local regulation) is (are) not able to comply with the clinical protocol.

• The participant has had previous treatment with alglucosidase alfa or any investigational therapy for Pompe disease.

• The participant has prior or current use of immune tolerance induction therapy.

• The participant, if female and of childbearing potential, has a positive pregnancy test (beta-human chorionic gonadotropin) at baseline.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 8400015	Phoenix	Arizona	United States	85013
2	Investigational Site Number 8400020	Los Angeles	California	United States	90095
3	Investigational Site Number 8400011	Orange	California	United States	92868
4	Investigational Site Number 8400017	Stanford	California	United States	94305
5	Investigational Site Number 8400016	Gainesville	Florida	United States	32610
6	Investigational Site Number 8400007	Decatur	Georgia	United States	30033
7	Investigational Site Number 8400023	Chicago	Illinois	United States	60611
8	Investigational Site Number 8400002	Iowa City	Iowa	United States	52242
9	Investigational Site Number 8400012	Kansas City	Kansas	United States	66160-7321
10	Investigational Site Number 8400010	Boston	Massachusetts	United States	02114
11	Investigational Site Number 8400001	Detroit	Michigan	United States	48201
12	Investigational Site Number 8400019	Minneapolis	Minnesota	United States	55455
13	Investigational Site Number 8400026	Great Neck	New York	United States	11020
14	Investigational Site Number 8400008	Valhalla	New York	United States	10595
15	Investigational Site Number 8400006	Durham	North Carolina	United States	27710
16	Investigational Site Number 8400009	Cincinnati	Ohio	United States	45267-0542
17	Investigational Site Number 8400014	Portland	Oregon	United States	97239
18	Investigational Site Number 8400025	Pittsburgh	Pennsylvania	United States	15213
19	Investigational Site Number 8400018	Salt Lake City	Utah	United States	84132
20	Investigational Site Number 8400005	Fairfax	Virginia	United States	22030
21	Investigational Site Number 8400024	Morgantown	West Virginia	United States	26506
22	Investigational Site Number 0320001	Caba		Argentina	C1181ACH
23	Investigational Site Number 0360001	Auchenflower		Australia	4066
24	Investigational Site Number 0400001	Wien		Austria	1090
25	Investigational Site Number 0560003	Bruxelles		Belgium	1070
26	Investigational Site Number 0560001	Leuven		Belgium	3000
27	Investigational Site Number 0760004	Brasilia		Brazil	71625-009
28	Investigational Site Number 0760001	Sao Paulo		Brazil	04037-002
29	Investigational Site Number 1240003	Hamilton		Canada	L8N 3Z5
30	Investigational Site Number 1240002	Montreal		Canada	H3A 2B4
31	Investigational Site Number 2030001	Praha 2		Czechia	12808
32	Investigational Site Number 2080003	København Ø		Denmark	2100
33	Investigational Site Number 2500008	Angers		France	49933
34	Investigational Site Number 2500007	Bordeaux		France
35	Investigational Site Number 2500011	Brest Cedex 2		France	29609
36	Investigational Site Number 2500004	Bron		France	69677
37	Investigational Site Number 2500010	Clermont Ferrand		France	63003
38	Investigational Site Number 2500005	Lille		France	59037
39	Investigational Site Number 2500006	Marseille Cedex 5		France	13385
40	Investigational Site Number 2500001	Paris		France	75013
41	Investigational Site Number 2760006	Bochum		Germany	44789
42	Investigational Site Number 2760001	Mainz		Germany	55131
43	Investigational Site Number 2760003	München		Germany	80336
44	Investigational Site Number 2760002	Münster		Germany	48149
45	Investigational Site Number 3480001	Budapest		Hungary	1083
46	Investigational Site Number 3800006	Brescia		Italy	25123
47	Investigational Site Number 3800001	Messina		Italy	98125
48	Investigational Site Number 3800002	Milano		Italy	20122
49	Investigational Site Number 3800007	Napoli		Italy	80131
50	Investigational Site Number 3800003	Torino		Italy	10126
51	Investigational Site Number 3920002	Kodaira-Shi		Japan
52	Investigational Site Number 4100001	Seoul		Korea, Republic of	03080
53	Investigational Site Number 4100002	Seoul		Korea, Republic of	06273
54	Investigational Site Number 4840001	Mexico		Mexico
55	Investigational Site Number 5280001	Rotterdam		Netherlands	3015 GE
56	Investigational Site Number 6160001	Warszawa		Poland	02-097
57	Investigational Site Number 6200001	Braga		Portugal	4710-243
58	Investigational Site Number 6430001	Moscow		Russian Federation	125367
59	Investigational Site Number 7240002	Barcelona		Spain	08025
60	Investigational Site Number 7240003	Barcelona		Spain	08950
61	Investigational Site Number 7560002	Zürich		Switzerland	8091
62	Investigational Site Number 1580001	Taipei		Taiwan	10043
63	Investigational Site Number 7920001	Ankara		Turkey	06100
64	Investigational Site Number 7920002	Istanbul		Turkey	34390
65	Investigational Site Number 8260005	Birmingham		United Kingdom	B15 2GW
66	Investigational Site Number 8260002	Cambridge		United Kingdom	CB2 OQQ
67	Investigational Site Number 8260001	London		United Kingdom	NW3 2QG
68	Investigational Site Number 8260004	Newcastle Upon Tyne		United Kingdom	NE1 4LP
69	Investigational Site Number 8260003	Salford		United Kingdom	M6 8HD

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

• Study Protocol - Dec 21, 2020
• Statistical Analysis Plan - Apr 14, 2020

More Information

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT02782741
• Other Study ID Numbers: EFC14028; 2016-000942-77; U1111-1178-4806
• First Posted: May 25, 2016
• Last Update Posted: May 27, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Glycogen Storage Disease Type II; Glycogen Storage Disease

Study Results

Participant Flow

Recruitment Details

The study was conducted at 69 active centers in 26 countries. A total of 146 participants were screened between 02 November 2016 and 22 March 2019, of which 100 participants were enrolled and randomized in the study by centralized treatment allocation system/interactive response technology (1:1 ratio) to receive avalglucosidase alfa or alglucosidase alfa. A total of 46 participants were screen failure mainly due to meeting exclusion criteria.

Pre-assignment Detail

Randomization was stratified by baseline percent (%) predicted forced vital capacity (FVC): less than (<) 55% or greater than or equal to (>=) 55%, gender, age (<18 years and >=18 years), and country (Japan or ex-Japan). Data reported based on primary completion date, i.e. 19 March 2020.

Arm/Group Title	Avalglucosidase Alfa	Alglucosidase Alfa in PAP Then Avalglucosidase Alfa in Open-label
Arm/Group Description	Avalglucosidase alfa, 20 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks (q2w) up to Week 49 in blinded treatment period (also known as primary analysis period [PAP]); followed by same treatment from Week 50 to 145 in an open-label avalglucosidase alfa long-term follow-up phase.	Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP); followed by avalglucosidase alfa 20 mg/kg IV infusion q2w treatment from Week 50 to 145 in an open-label avalglucosidase alfa long-term follow-up phase.
Period Title: Blinded Treatment Period: up to Week 49
STARTED	51	49
Safety Population	51	49
COMPLETED	51	44
NOT COMPLETED	0	5
Period Title: Blinded Treatment Period: up to Week 49
STARTED	51	44
Safety Population	51	44
COMPLETED	0	0
NOT COMPLETED	51	44

Baseline Characteristics

Arm/Group Title	Avalglucosidase Alfa	Alglucosidase Alfa in PAP Then Avalglucosidase Alfa in Open-label	Total
Arm/Group Description	Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP); followed by same treatment from Week 50 to 145 in an open-label avalglucosidase alfa long-term follow-up phase.	Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP); followed by avalglucosidase alfa 20 mg/kg IV infusion q2w treatment from Week 50 to 145 in an open-label avalglucosidase alfa long-term follow-up phase.	Total of all reporting groups
Overall Participants	51	49	100
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.0 (14.5)	50.3 (13.7)	48.1 (14.2)
Sex: Female, Male (Count of Participants)
Female	24 47.1%	24 49%	48 48%
Male	27 52.9%	25 51%	52 52%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 5.9%	0 0%	3 3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 2%	2 4.1%	3 3%
White	47 92.2%	47 95.9%	94 94%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Percent Predicted Forced Vital Capacity (FVC) in Upright Position (percent predicted FVC) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percent predicted FVC]	62.5 (14.4)	61.6 (12.4)	62.1 (13.4)

Outcome Measures

1. Primary Outcome

Title	PAP: Change From Baseline in Percent Predicted Forced Vital Capacity in Upright Position at Week 49
Description	FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Least square (LS) mean and standard error (SE) were derived from mixed model for repeated measure (MMRM) model with baseline FVC (% predicted, as continuous), sex, age (in years at baseline), treatment group, visit, interaction term between treatment group and visit as fixed effects. Percent of predicted FVC = (actual FVC measurement)/(predicted value of FVC) * 100. After non-inferiority (NI) testing, a test for superiority of avalglucosidase alfa versus alglucosidase alfa was performed with an overall 2-sided 5% level of significance.
Time Frame	Baseline, Week 49

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population.

Arm/Group Title	PAP: Avalglucosidase Alfa	PAP: Alglucosidase Alfa
Arm/Group Description	Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).
Measure Participants	51	49
Least Squares Mean (Standard Error) [percent predicted FVC]	2.89 (0.88)	0.46 (0.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PAP: Avalglucosidase Alfa, PAP: Alglucosidase Alfa
	Comments	Analysis performed using MMRM model with baseline FVC (% predicted, as continuous), sex, age (in years at baseline), treatment group, visit, interaction term between treatment group and visit as fixed effects.
	Type of Statistical Test	Non-Inferiority
	Comments	NI was demonstrated if the lower bound of the 2-sided 95% confidence interval (CI) for the difference of avalglucosidase alfa minus alglucosidase alfa was greater than (>) -1.1.
Statistical Test of Hypothesis	p-Value	0.0074
	Comments
	Method	mixed model for repeated measures
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	2.43
	Confidence Interval	(2-Sided) 95%; -0.13 to 4.99
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.29
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PAP: Avalglucosidase Alfa, PAP: Alglucosidase Alfa
	Comments	Analysis performed using MMRM model with baseline FVC (% predicted, as continuous), sex, age (in years at baseline), treatment group, visit, interaction term between treatment group and visit as fixed effects.
	Type of Statistical Test	Superiority
	Comments	A test for superiority of avalglucosidase alfa versus alglucosidase alfa was performed with an overall 5% level of significance.
Statistical Test of Hypothesis	p-Value	0.0626
	Comments	Threshold for significance at <0.05 level.
	Method	mixed model for repeated measures
	Comments

2. Secondary Outcome

Title	PAP: Change From Baseline in Total Distance Walked During Six-minute Walk Test (6MWT) at Week 49
Description	6MWT was a standardized test that measured the distance (in meters) covered by the participant by walking on a flat, hard surface in a period of a 6-minute walk. Mean distance walked gives an indication of functional endurance. The greater the distance (that a participant could walk in 6 minutes), the greater the endurance. LS mean and SE were derived from MMRM model with baseline FVC (% predicted) and baseline 6MWT (distance walked in meter), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.
Time Frame	Baseline, Week 49

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population.

Arm/Group Title	PAP: Avalglucosidase Alfa	PAP: Alglucosidase Alfa
Arm/Group Description	Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).
Measure Participants	51	49
Least Squares Mean (Standard Error) [meters]	32.21 (9.93)	2.19 (10.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PAP: Avalglucosidase Alfa, PAP: Alglucosidase Alfa
	Comments	LS mean difference was derived from MMRM model with baseline FVC (% predicted) and baseline 6MWT (distance walked in meter), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.
	Type of Statistical Test	Other
	Comments	Per the protocol-defined statistical test strategy for multiplicity adjustment, and since superiority was narrowly missed for FVC % predicted, superiority testing for the secondary outcome measure couldn't be performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	30.01
	Confidence Interval	(2-Sided) 95%; 1.33 to 58.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 14.43
	Estimation Comments

3. Secondary Outcome

Title	PAP: Change From Baseline in Percent Predicted Maximal Inspiratory Pressure (MIP) in Upright Position at Week 49
Description	MIP is a quick and non-invasive test to measure strength of inspiratory muscles, primarily diaphragm, and allows for assessment of ventilatory failure, restrictive lung disease and respiratory muscle strength. MIP refers to how much air pressure force an individual creates by inhaling through the mouth as hard as possible. LS mean and SE were derived from MMRM model for MIP % predicted adjusted for MIP % predicted at baseline, age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.
Time Frame	Baseline, Week 49

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population.

Arm/Group Title	PAP: Avalglucosidase Alfa	PAP: Alglucosidase Alfa
Arm/Group Description	Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).
Measure Participants	51	49
Least Squares Mean (Standard Error) [percent predicted MIP]	-0.29 (3.84)	-2.87 (4.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PAP: Avalglucosidase Alfa, PAP: Alglucosidase Alfa
	Comments	LS mean difference was derived from MMRM model for MIP % predicted adjusted for MIP % predicted at baseline, age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.
	Type of Statistical Test	Other
	Comments	Per the protocol-defined statistical test strategy for multiplicity adjustment, and since superiority was narrowly missed for FVC % predicted, superiority testing for the secondary outcome measure couldn't be performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	2.58
	Confidence Interval	(2-Sided) 95%; -8.54 to 13.71
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.59
	Estimation Comments

4. Secondary Outcome

Title	PAP: Change From Baseline in Percent Predicted Maximal Expiratory Pressure (MEP) in Upright Position at Week 49
Description	MEP is a quick and non-invasive test to measure strength of expiratory muscles, primarily diaphragm, and allows for assessment of ventilatory failure, restrictive lung disease and respiratory muscle strength. MEP is the greater pressure generated during maximal expiration. LS mean and SE were derived from MMRM model for MEP % predicted adjusted for MEP % predicted at baseline, age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.
Time Frame	Baseline, Week 49

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population.

Arm/Group Title	PAP: Avalglucosidase Alfa	PAP: Alglucosidase Alfa
Arm/Group Description	Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).
Measure Participants	51	49
Least Squares Mean (Standard Error) [percent predicted MEP]	2.39 (4.00)	5.00 (4.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PAP: Avalglucosidase Alfa, PAP: Alglucosidase Alfa
	Comments	LS mean difference was derived from MMRM model for MEP % predicted adjusted for MEP % predicted at baseline, age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.
	Type of Statistical Test	Other
	Comments	Per the protocol-defined statistical test strategy for multiplicity adjustment, and since superiority was narrowly missed for FVC % predicted, superiority testing for the secondary outcome measure couldn't be performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	-2.61
	Confidence Interval	(2-Sided) 95%; -14.22 to 9.00
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.83
	Estimation Comments

5. Secondary Outcome

Title	PAP: Change From Baseline in Lower Extremity Muscle Strength at Week 49 as Assessed by Hand-held Dynamometry (HHD)
Description	HHD: a portable method for strength quantitation. To complete a make test, participant exerted maximal force against dynamometer with gradual increase in force and completed isometric hold for 4-5 seconds. Muscle strengths were collected in Newton. Every muscle group (hip: flexion, extension, abduction; knee: flexion, extension and ankle dorsiflexion) were measured 2 times and highest value was reported. Summary score was sum of 12 measurements (2 measurements per muscle group) from 6 muscle groups on each side (left and right). An increase from Baseline was reflective of increased muscle strength, whereas a decrease from Baseline was reflective of decreased muscle strength. LS mean and SE were derived from MMRM model for HHD lower extremity muscle strength composite score adjusted for summary HHD lower extremity score at baseline, baseline FVC (% predicted), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.
Time Frame	Baseline, Week 49

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population.

Arm/Group Title	PAP: Avalglucosidase Alfa	PAP: Alglucosidase Alfa
Arm/Group Description	Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).
Measure Participants	51	49
Least Squares Mean (Standard Error) [Newton]	260.69 (46.07)	153.72 (48.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PAP: Avalglucosidase Alfa, PAP: Alglucosidase Alfa
	Comments	LS mean difference was derived from MMRM model for HHD lower extremity muscle strength composite score adjusted for summary HHD lower extremity score at baseline, baseline FVC (% predicted), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.
	Type of Statistical Test	Other
	Comments	Per the protocol-defined statistical test strategy for multiplicity adjustment, and since superiority was narrowly missed for FVC % predicted, superiority testing for the secondary outcome measure couldn't be performed.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	LS mean difference
	Estimated Value	106.97
	Confidence Interval	(2-Sided) 95%; -26.56 to 240.50
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 67.17
	Estimation Comments

6. Secondary Outcome

Title	PAP: Change From Baseline in Quick Motor Function Test (QMFT) Total Scores at Week 49
Description	The QMFT was an observer administered test to evaluate changes in motor function. QMFT comprised of 16 items specifically difficult for participants with Pompe disease. Each item was scored separately on a 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), higher score represented better outcome. LS mean and SE were derived from MMRM models adjusted for total QMFT score at baseline, baseline FVC (% predicted), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.
Time Frame	Baseline, Week 49

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population.

Arm/Group Title	PAP: Avalglucosidase Alfa	PAP: Alglucosidase Alfa
Arm/Group Description	Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).
Measure Participants	51	49
Least Squares Mean (Standard Error) [scores on a scale]	3.98 (0.63)	1.89 (0.69)

7. Secondary Outcome

Title	PAP: Change From Baseline in 12-item Short-form Health Survey (SF-12): Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 49
Description	SF-12, a 12 item-questionnaire, used to assess health-related quality of life in participants aged >=18 years at screening/baseline. SF-12 consisted of 12 items, which were categorized into eight domains (subscales) of functioning and well-being: physical functioning, role-physical, role emotional, mental health, bodily pain, general health, vitality and social functioning, with each domain score ranged from 0 (poor health) to 100 (better health), higher scores indicated good health condition. These eight domains were further summarized into 2 summary scores, PCS and MCS. The score range for each of these 2 summary scores was from 0 (poor health) to 100 (better health), higher scores indicated a better health-related quality of life. LS mean and SE were derived from MMRM models adjusted for baseline score (PCS or MCS), baseline FVC (% predicted), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.
Time Frame	Baseline, Week 49

Outcome Measure Data

Analysis Population Description

Analysis was performed on mITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	PAP: Avalglucosidase Alfa	PAP: Alglucosidase Alfa
Arm/Group Description	Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).
Measure Participants	50	49
PCS score	2.37 (0.99)	1.60 (1.07)
MCS score	2.88 (1.22)	0.76 (1.32)

8. Secondary Outcome

Title	PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Infusion-associated Reactions (IARs)
Description	AE: any untoward medical occurrence in participant who took study drug and not necessarily have to had causal relationship with treatment. TEAEs: AEs that developed/worsened in grade/became serious during TEAE period in PAP (from time of 1st treatment date to last treatment date+4 weeks for participants who didn't receive any treatment in open-label or to time just prior to 1st treatment in open-label for participants who received treatment in open-label). Protocol-defined IARs: AE of special interest (AESIs) that occurred during either infusion/observation period following infusion which were deemed to be related/possibly related to study drug. Algorithm-defined IARs: any TEAE meeting either 1 of 2 criteria: 1) event occurred from start to end of infusion + 24 hours, considered related to study drug, 2) If AE time component missed, compare AE start date with infusion start and end date. If AE start date was between infusion start and end date + 1 day and it was related to study drug.
Time Frame	From Baseline up to Week 49

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population which included participants who had received at least 1 infusion (partial or total) and were analyzed according to the treatment received.

Arm/Group Title	PAP: Avalglucosidase Alfa	PAP: Alglucosidase Alfa
Arm/Group Description	Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).
Measure Participants	51	49
Any TEAE	44 86.3%	45 91.8%
Any Protocol-defined IARs	13 25.5%	16 32.7%
Any Algorithm-defined IARs	15 29.4%	20 40.8%

9. Secondary Outcome

Title	Open-label Period: Number of Participants With Treatment-emergent Adverse Events and Infusion-associated Reactions
Description	AE: any untoward medical occurrence in a participant who received study drug and did not necessarily have to had a causal relationship with treatment. TEAEs in open-label: AEs that developed/worsened in grade/became serious during TEAE period in open-label (from time of 1st open-label treatment to last treatment date + 4 weeks). Protocol-defined IARs: defined as AESIs that occurred during either infusion/observation period following infusion which were deemed to be related/possibly related to study drug. Algorithm-defined IARs: any TEAE meeting either 1 of 2 criteria: 1) event occurred from start to end of infusion plus 24 hours, considered related to study drug, 2) If AE time component missed, compare AE start date with infusion start and end date. If AE start date was between infusion start and end date plus 1 day and it was related to study drug.
Time Frame	Week 50 to 145 in open-label long-term period

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population.

Arm/Group Title	Avalglucosidase Alfa	Alglucosidase Alfa in PAP Then Avalglucosidase Alfa in Open-label
Arm/Group Description	Included all participants who received avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in PAP; followed the same treatment from Week 50 to 145 in an open-label avalglucosidase alfa long-term follow-up phase.	Included all participants who received alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in PAP; followed by avalglucosidase alfa 20 mg/kg IV infusion q2w treatment from Week 50 to 145 in an open-label avalglucosidase alfa long-term follow-up phase.
Measure Participants	51	44
Any TEAE	40 78.4%	35 71.4%
Any Protocol-defined IARs	6 11.8%	15 30.6%
Any Algorithm-defined IARs	8 15.7%	17 34.7%

10. Secondary Outcome

Title	PAP: Percentage of Participants With Treatment-emergent Antidrug Antibodies (ADA) Response
Description	ADA response categories: 1) Treatment-induced: ADAs developed following administration of the study drug. If the baseline ADA sample was missing or non-reportable and at least one reportable on-treatment ADA sample was available, the baseline sample was considered as "negative". 2) Treatment-boosted: Pre-existing ADAs that were boosted at least two titer steps from baseline (i.e., 4 fold increase in titers) following administration of the study drug (any time after the first drug administration). 3) Treatment emergent: combination of treatment induced and treatment boosted.
Time Frame	From Baseline up to Week 49

Outcome Measure Data

Analysis Population Description

Analysis was performed on ADA evaluable population which consisted of 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/Group Title	PAP: Avalglucosidase Alfa	PAP: Alglucosidase Alfa
Arm/Group Description	Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).	Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).
Measure Participants	51	48
Treatment-Induced	95.9 188%	95.7 195.3%
Treatment-boosted ADA	100 196.1%	100 204.1%
Treatment emergent ADA	96.1 188.4%	95.8 195.5%

Adverse Events

Time Frame	Up to Week 49 in PAP and from Week 50 to 145 in open-label long-term period
Adverse Event Reporting Description	Reported AEs and deaths were treatment emergent AEs that developed/worsened in grade or became serious during 'TEAE period' (for PAP: from 1st study drug treatment date to the last study treatment date + 4 weeks for participants not exposed to treatment in open-label or to time just prior to 1st dose in open-label for those exposed to open-label) (for open-label: time from 1st study drug treatment in open-label to last study treatment + 4 weeks). Analyzed on safety population.
Arm/Group Title	PAP: Avalglucosidase Alfa		PAP: Alglucosidase Alfa		Open-label Period: Avalglucosidase Alfa		Open-label Period: Alglucosidase Alfa in PAP Then Avalglucosidase Alfa in Open-label
Arm/Group Description	Avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).		Alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in blinded treatment period (also known as PAP).		Included all participants who received avalglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in PAP followed by same treatment from Week 50 to 145 in an open-label avalglucosidase alfa long-term follow-up phase.		Included all participants who received alglucosidase alfa, 20 mg/kg IV infusion q2w up to Week 49 in PAP; followed by avalglucosidase alfa 20 mg/kg IV infusion q2w treatment from Week 50 to 145 in an open-label avalglucosidase alfa long-term follow-up phase.
All Cause Mortality
	PAP: Avalglucosidase Alfa		PAP: Alglucosidase Alfa		Open-label Period: Avalglucosidase Alfa		Open-label Period: Alglucosidase Alfa in PAP Then Avalglucosidase Alfa in Open-label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		1/49 (2%)		0/51 (0%)		0/44 (0%)
Serious Adverse Events
	PAP: Avalglucosidase Alfa		PAP: Alglucosidase Alfa		Open-label Period: Avalglucosidase Alfa		Open-label Period: Alglucosidase Alfa in PAP Then Avalglucosidase Alfa in Open-label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/51 (15.7%)		12/49 (24.5%)		8/51 (15.7%)		5/44 (11.4%)
Cardiac disorders
Acute Myocardial Infarction	0/51 (0%)	0	1/49 (2%)	1	1/51 (2%)	1	0/44 (0%)	0
Angina Pectoris	0/51 (0%)	0	1/49 (2%)	1	0/51 (0%)	0	1/44 (2.3%)	1
Supraventricular Tachycardia	0/51 (0%)	0	1/49 (2%)	1	0/51 (0%)	0	0/44 (0%)	0
Ear and labyrinth disorders
Vertigo	0/51 (0%)	0	0/49 (0%)	0	0/51 (0%)	0	1/44 (2.3%)	1
Endocrine disorders
Inappropriate Antidiuretic Hormone Secretion	0/51 (0%)	0	1/49 (2%)	1	0/51 (0%)	0	0/44 (0%)	0
Eye disorders
Visual Impairment	0/51 (0%)	0	1/49 (2%)	1	0/51 (0%)	0	0/44 (0%)	0
Gastrointestinal disorders
Abdominal Pain Upper	0/51 (0%)	0	1/49 (2%)	1	0/51 (0%)	0	0/44 (0%)	0
Gastrointestinal Haemorrhage	0/51 (0%)	0	1/49 (2%)	1	0/51 (0%)	0	0/44 (0%)	0
Nausea	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	2	0/44 (0%)	0
General disorders
Chills	0/51 (0%)	0	1/49 (2%)	1	1/51 (2%)	1	0/44 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Cholelithiasis	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Infections and infestations
Bacteraemia	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Pneumonia	1/51 (2%)	1	1/49 (2%)	1	1/51 (2%)	1	0/44 (0%)	0
Sepsis	0/51 (0%)	0	1/49 (2%)	1	0/51 (0%)	0	0/44 (0%)	0
Injury, poisoning and procedural complications
Hip Fracture	0/51 (0%)	0	0/49 (0%)	0	0/51 (0%)	0	1/44 (2.3%)	1
Viiith Nerve Injury	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Investigations
Blood Pressure Increased	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Body Temperature Increased	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Haemoglobin Decreased	0/51 (0%)	0	1/49 (2%)	1	0/51 (0%)	0	0/44 (0%)	0
Heart Rate Increased	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Oxygen Saturation Decreased	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Metabolism and nutrition disorders
Hyponatraemia	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma Pancreas	0/51 (0%)	0	0/49 (0%)	0	0/51 (0%)	0	1/44 (2.3%)	1
Renal Oncocytoma	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Nervous system disorders
Brain Stem Stroke	0/51 (0%)	0	1/49 (2%)	1	0/51 (0%)	0	0/44 (0%)	0
Cerebellar Ischaemia	0/51 (0%)	0	1/49 (2%)	1	0/51 (0%)	0	0/44 (0%)	0
Dizziness	0/51 (0%)	0	1/49 (2%)	1	0/51 (0%)	0	0/44 (0%)	0
Headache	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Moyamoya Disease	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Subarachnoid Haemorrhage	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Syncope	1/51 (2%)	1	0/49 (0%)	0	0/51 (0%)	0	0/44 (0%)	0
Psychiatric disorders
Bipolar Disorder	0/51 (0%)	0	0/49 (0%)	0	0/51 (0%)	0	1/44 (2.3%)	2
Renal and urinary disorders
Calculus Urinary	1/51 (2%)	1	0/49 (0%)	0	0/51 (0%)	0	0/44 (0%)	0
Hydronephrosis	1/51 (2%)	1	0/49 (0%)	0	0/51 (0%)	0	0/44 (0%)	0
Nephrolithiasis	0/51 (0%)	0	1/49 (2%)	2	0/51 (0%)	0	0/44 (0%)	0
Pelvi-Ureteric Obstruction	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Renal Colic	1/51 (2%)	1	0/49 (0%)	0	0/51 (0%)	0	0/44 (0%)	0
Reproductive system and breast disorders
Breast Cyst	1/51 (2%)	1	0/49 (0%)	0	0/51 (0%)	0	0/44 (0%)	0
Respiratory, thoracic and mediastinal disorders
Diaphragmatic Paralysis	0/51 (0%)	0	1/49 (2%)	1	0/51 (0%)	0	0/44 (0%)	0
Dyspnoea	1/51 (2%)	1	2/49 (4.1%)	2	0/51 (0%)	0	0/44 (0%)	0
Hypoventilation	1/51 (2%)	1	0/49 (0%)	0	0/51 (0%)	0	0/44 (0%)	0
Pulmonary Embolism	0/51 (0%)	0	1/49 (2%)	1	0/51 (0%)	0	0/44 (0%)	0
Respiratory Acidosis	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Respiratory Failure	1/51 (2%)	2	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Skin and subcutaneous tissue disorders
Cold Sweat	0/51 (0%)	0	1/49 (2%)	1	0/51 (0%)	0	0/44 (0%)	0
Skin Discolouration	0/51 (0%)	0	0/49 (0%)	0	1/51 (2%)	1	0/44 (0%)	0
Vascular disorders
Hypotension	0/51 (0%)	0	1/49 (2%)	1	0/51 (0%)	0	0/44 (0%)	0
Other (Not Including Serious) Adverse Events
	PAP: Avalglucosidase Alfa		PAP: Alglucosidase Alfa		Open-label Period: Avalglucosidase Alfa		Open-label Period: Alglucosidase Alfa in PAP Then Avalglucosidase Alfa in Open-label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	40/51 (78.4%)		44/49 (89.8%)		32/51 (62.7%)		32/44 (72.7%)
Eye disorders
Conjunctival Haemorrhage	0/51 (0%)	0	0/49 (0%)	0	0/51 (0%)	0	3/44 (6.8%)	4
Gastrointestinal disorders
Abdominal Pain	1/51 (2%)	1	1/49 (2%)	1	3/51 (5.9%)	3	1/44 (2.3%)	1
Abdominal Pain Upper	2/51 (3.9%)	4	2/49 (4.1%)	2	3/51 (5.9%)	6	1/44 (2.3%)	2
Diarrhoea	6/51 (11.8%)	9	8/49 (16.3%)	9	6/51 (11.8%)	11	10/44 (22.7%)	13
Dyspepsia	3/51 (5.9%)	9	3/49 (6.1%)	5	1/51 (2%)	1	0/44 (0%)	0
Nausea	6/51 (11.8%)	8	7/49 (14.3%)	15	6/51 (11.8%)	7	5/44 (11.4%)	18
Vomiting	4/51 (7.8%)	5	3/49 (6.1%)	3	3/51 (5.9%)	3	6/44 (13.6%)	7
General disorders
Fatigue	9/51 (17.6%)	11	7/49 (14.3%)	27	2/51 (3.9%)	4	5/44 (11.4%)	9
Influenza Like Illness	3/51 (5.9%)	5	1/49 (2%)	1	3/51 (5.9%)	4	0/44 (0%)	0
Infusion Site Extravasation	0/51 (0%)	0	3/49 (6.1%)	3	0/51 (0%)	0	3/44 (6.8%)	5
Non-Cardiac Chest Pain	3/51 (5.9%)	5	0/49 (0%)	0	0/51 (0%)	0	0/44 (0%)	0
Oedema Peripheral	3/51 (5.9%)	4	3/49 (6.1%)	3	2/51 (3.9%)	4	0/44 (0%)	0
Pain	2/51 (3.9%)	3	5/49 (10.2%)	13	1/51 (2%)	3	6/44 (13.6%)	14
Pyrexia	2/51 (3.9%)	2	4/49 (8.2%)	4	3/51 (5.9%)	3	2/44 (4.5%)	3
Infections and infestations
Bronchitis	0/51 (0%)	0	2/49 (4.1%)	2	0/51 (0%)	0	3/44 (6.8%)	3
Cystitis	3/51 (5.9%)	4	0/49 (0%)	0	0/51 (0%)	0	0/44 (0%)	0
Influenza	9/51 (17.6%)	10	2/49 (4.1%)	3	4/51 (7.8%)	4	3/44 (6.8%)	3
Nasopharyngitis	12/51 (23.5%)	16	12/49 (24.5%)	17	8/51 (15.7%)	10	10/44 (22.7%)	15
Upper Respiratory Tract Infection	4/51 (7.8%)	5	2/49 (4.1%)	2	3/51 (5.9%)	3	6/44 (13.6%)	8
Injury, poisoning and procedural complications
Contusion	5/51 (9.8%)	5	4/49 (8.2%)	4	2/51 (3.9%)	3	1/44 (2.3%)	1
Fall	7/51 (13.7%)	12	10/49 (20.4%)	13	4/51 (7.8%)	11	5/44 (11.4%)	7
Investigations
Alanine Aminotransferase Increased	2/51 (3.9%)	2	3/49 (6.1%)	3	1/51 (2%)	1	2/44 (4.5%)	2
Musculoskeletal and connective tissue disorders
Arthralgia	5/51 (9.8%)	6	8/49 (16.3%)	10	5/51 (9.8%)	5	5/44 (11.4%)	10
Back Pain	12/51 (23.5%)	15	5/49 (10.2%)	7	3/51 (5.9%)	5	6/44 (13.6%)	9
Muscle Spasms	3/51 (5.9%)	3	5/49 (10.2%)	5	3/51 (5.9%)	3	3/44 (6.8%)	4
Muscular Weakness	0/51 (0%)	0	3/49 (6.1%)	6	0/51 (0%)	0	1/44 (2.3%)	3
Musculoskeletal Pain	1/51 (2%)	1	2/49 (4.1%)	2	3/51 (5.9%)	5	5/44 (11.4%)	5
Myalgia	5/51 (9.8%)	15	7/49 (14.3%)	12	4/51 (7.8%)	7	3/44 (6.8%)	4
Pain In Extremity	8/51 (15.7%)	9	7/49 (14.3%)	14	5/51 (9.8%)	6	5/44 (11.4%)	8
Nervous system disorders
Dizziness	5/51 (9.8%)	6	3/49 (6.1%)	14	5/51 (9.8%)	7	2/44 (4.5%)	3
Headache	11/51 (21.6%)	32	16/49 (32.7%)	102	6/51 (11.8%)	23	11/44 (25%)	28
Paraesthesia	3/51 (5.9%)	3	2/49 (4.1%)	2	0/51 (0%)	0	1/44 (2.3%)	1
Respiratory, thoracic and mediastinal disorders
Cough	2/51 (3.9%)	2	4/49 (8.2%)	4	2/51 (3.9%)	3	3/44 (6.8%)	4
Nasal Congestion	1/51 (2%)	1	5/49 (10.2%)	5	1/51 (2%)	1	1/44 (2.3%)	1
Oropharyngeal Pain	2/51 (3.9%)	2	5/49 (10.2%)	8	1/51 (2%)	4	2/44 (4.5%)	3
Skin and subcutaneous tissue disorders
Erythema	3/51 (5.9%)	4	3/49 (6.1%)	7	2/51 (3.9%)	3	0/44 (0%)	0
Pruritus	4/51 (7.8%)	5	4/49 (8.2%)	9	1/51 (2%)	1	7/44 (15.9%)	33
Rash	2/51 (3.9%)	11	4/49 (8.2%)	4	4/51 (7.8%)	7	5/44 (11.4%)	7
Urticaria	3/51 (5.9%)	4	1/49 (2%)	5	2/51 (3.9%)	3	4/44 (9.1%)	5
Vascular disorders
Flushing	0/51 (0%)	0	3/49 (6.1%)	3	0/51 (0%)	0	1/44 (2.3%)	2
Hypertension	1/51 (2%)	2	3/49 (6.1%)	5	1/51 (2%)	1	1/44 (2.3%)	1
Hypotension	0/51 (0%)	0	1/49 (2%)	1	3/51 (5.9%)	4	0/44 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.