An Exploratory Study of the Safety and Efficacy of Prophylactic Immunomodulatory Treatment in Myozyme-naive Cross-Reacting Immunologic Material (CRIM[-]) Patients With Infantile-Onset Pompe Disease

• Sponsor: Genzyme, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Genzyme, a Sanofi Company )

Study Type	Interventional
Study Design	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Pompe Disease; Glycogen Storage Disease Type II
Interventions	Biological: Alglucosidase Alfa; Drug: Methotrexate; Drug: Rituximab
Enrollment	4

Participant Flow

Recruitment Details	The study was conducted at 2 centers in the United States of America between October 01, 2009 and March 27, 2013.
Pre-assignment Details

Arm/Group Title	Alglucosidase Alfa
Arm/Group Description	Alglucosidase alfa (Myozyme®) 20 milligrams per kilogram (mg/kg) intravenous (IV) infusion every other week (qow) (or optionally 20 mg/kg IV infusion every week [qw]) beginning from Day 0 to a minimum of 18 months or if the patient was less than (<) 6 months of age at the time of enrollment, until the patient was 2 years of age, along with methotrexate 0.4 mg/kg subcutaneously for 3 consecutive days qow beginning from Day 0 to Week 6 (9 doses) and rituximab 375 milligrams per square meter (mg/m^2) (or 12.5 mg/kg for patients with body surface area less than or equal to 0.5 m^2) IV infusion qw beginning from Day -1 to Week 4 (4 doses) as per local prescribing information. An additional 4-week cycle of rituximab (up to 4 additional doses) and 6-week cycle of methotrexate (up to 9 additional doses) may have been administered within the first 6 months of the study as per local prescribing information.
Period Title: Overall Study
Started	4
Full Analysis Set (FAS)	4 [1]
Completed	2
Not Completed	2
Reason Not Completed
Death	2
[1] All enrolled patients who signed informed consent, received at least 1 dose of alglucosidase alfa.

Baseline Characteristics

Arm/Group Title		Alglucosidase Alfa
Arm/Group Description		Alglucosidase alfa (Myozyme®) 20 mg/kg IV infusion qow (or optionally 20 mg/kg IV infusion every week [qw]) beginning from Day 0 to a minimum of 18 months or if the patient was <6 months of age at the time of enrollment, until the patient was 2 years of age, along with methotrexate 0.4 mg/kg subcutaneously for 3 consecutive days qow beginning from Day 0 to Week 6 (9 doses) and rituximab 375 mg/m^2 (or 12.5 mg/kg for patients with body surface area less than or equal to 0.5 m^2) IV infusion qw beginning from Day -1 to Week 4 (4 doses) as per local prescribing information. An additional 4-week cycle of rituximab (up to 4 additional doses) and 6-week cycle of methotrexate (up to 9 additional doses) may have been administered within the first 6 months of the study as per local prescribing information.
Overall Number of Baseline Participants		4
Baseline Analysis Population Description		Safety population included all patients who received at least one dose of alglucosidase alfa.
Age, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	4 participants
Less Than or Equal to (=<) 6 Months		2
Greater Than (>) 6 Months		2
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	4 participants
	Female	3 75.0%
	Male	1 25.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	4 participants
Race: Black		2
Race: White		1
Race: White, Black		1
Ethnicity: Hispanic		2
Ethnicity: Non Hispanic		2
Number of Patients With Anti-Recombinant Human Acid Alfa-glucosidase (Anti-rhGAA) Immunoglobulin G [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	4 participants
Negative		4
Positive		0
		[1] Measure Description: As all patients were treatment naïve, it was expected that no patient would be Anti-rhGAA immunoglobulin G (IgG) antibody positive at baseline.
Number of Patients With Normal/Abnormal Left Ventricular Mass (LVM) Z-Score and LVM Index [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	4 participants
LVM Z-score: Normal		0
LVM Z-score: Abnormal		4
LVM index: Normal		0
LVM index: Abnormal		4
		[1] Measure Description: LVM Z-Score and LVM Index were assessed by echocardiography (ECHO). LVM Z-Score: an indicator of degree of standard deviations from mean in a normal distribution. Negative values indicate a smaller LVM than mean and values higher than 0 indicate a larger LVM than mean. Normal range is -2 to 2; values <-2 or >2 indicate abnormal score. LVM index: an index value derived by normalizing LVM by body surface area. LVM index provides evidence of cardiomyopathy. LVM index values <65 gram per square meter (g/m^2) were considered as normal and LVM index values >=65 g/m^2 were considered as abnormal.
Number of Patients With Ventilator Use; Measure Type: Number; Unit of measure: Participants	Number Analyzed	4 participants
Yes		3
No		1
Gross Motor Disability Assessed by Gross Motor Function Measure-88 (GMFM-88) [1]; Median (Full Range); Unit of measure: Percentage of maximum total score
	Number Analyzed	4 participants
		5.10; (0.39 to 7.49)
		[1] Measure Description: GMFM-88:an 88-item measure to detect gross motor function; consists of 5 categories: lying and rolling; sitting; crawling and kneeling; standing; walking, running and jumping. Each item is scored on a 4-point Likert scale(0=cannot do; 1=initiates [<10% of the task]; 2=partially completes [10% to <100% of the task]; 3=task completion). Score for each dimension is expressed as a percentage of maximum score for that dimension. Total score=sum of percentage scores for each dimension divided by number of dimensions. Total score range: 0% to 100%, where higher scores indicate better motor functions.
Motor Development Status Assessed by Alberta Infantile Motor Scale (AIMS) [1]; Median (Full Range); Unit of measure: Months
	Number Analyzed	4 participants
		0; (0 to 1.37)
		[1] Measure Description: AIMS:58-item in 4 subscales: prone; supine; sitting; and standing. Each item is scored as observed/not observed. Item in observed range create a motor window. Subscale scores are calculated by giving child 1 point for observed items within motor window in addition to being given 1 point for all less mature items before motor window. AIMS total score=sum of scores for 58 items, range: 0-58,higher score=more mature motor development. Score was then compared with age-equivalent peers from normative sample and equivalence level age (in months) is reported. Here, number of patients analyzed = 3.
Disability Index Assessed by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) [1]; Median (Full Range); Unit of measure: Units on a scale	Number Analyzed	4 participants
Functional Skills: Mobility Score (n=4)		4.5; (0 to 18.4)
Functional Skills: Self-Care Score (n=4)		14.4; (4.9 to 16.1)
Functional Skills: Social Function Score (n=1)		10.5; (10.5 to 10.5)
Caregiver Assistance: Mobility Score (n=2)		0; (0 to 0)
Caregiver Assistance: Self-Care Score (n=2)		0; (0 to 0)
Caregiver Assistance: Social Function Score (n=2)		0; (0 to 0)
		[1] Measure Description: It consists of all items of original PEDI (197 functional skill items in 3 domains:self-care;mobility;social function) and additional items in functional skills,mobility,self-care domains to reflect functional skills for children with Pompe. Each domain consists of 2 subdomains: functional skill performance, caregiver assistance scale. Norm-based scoring was developed for additional items, and scoring for PEDI have been adjusted to reflect additional normative data collected for Pompe PEDI. Total score range for each domain (mean of subdomains) and subdomain=0-100;higher score=high capability.

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Number of Patients With Anti-Recombinant Human Acid Alfa-glucosidase (Anti-rhGAA) Immunoglobulin G (IgG) Antibody at End of Study
Description	Serum samples from patients were analyzed for the presence of anti-rhGAA IgG antibodies. End of study (EOS) refers to the last post baseline observation during study period (up to Week 79).
Time Frame	Baseline, End of Study (up to Week 79 or early termination)

Outcome Measure Data

Analysis Population Description

FAS population included all enrolled patients who signed informed consent and received at least 1 dose of alglucosidase alfa.

Arm/Group Title	Alglucosidase Alfa
Arm/Group Description:	Alglucosidase alfa (Myozyme®) 20 mg/kg IV infusion qow (or optionally 20 mg/kg IV infusion every week [qw]) beginning from Day 0 to a minimum of 18 months or if the patient was <6 months of age at the time of enrollment, until the patient was 2 years of age, along with methotrexate 0.4 mg/kg subcutaneously for 3 consecutive days qow beginning from Day 0 to Week 6 (9 doses) and rituximab 375 mg/m^2 (or 12.5 mg/kg for patients with body surface area less than or equal to 0.5 m^2) IV infusion qw beginning from Day -1 to Week 4 (4 doses) as per local prescribing information. An additional 4-week cycle of rituximab (up to 4 additional doses) and 6-week cycle of methotrexate (up to 9 additional doses) may have been administered within the first 6 months of the study as per local prescribing information.
Overall Number of Participants Analyzed	4
Measure Type: Number; Unit of Measure: participants
Baseline - Negative; EOS - Positive	2
Baseline - Negative; EOS - Negative	2

2. Primary Outcome

Title	Number of Patients With Recombinant Human Acid Alfa-glucosidase (rhGAA) Inhibitory Antibody at End of Study
Description	Patients with positive anti-rhGAA IgG antibody were assessed for the presence of inhibitory antibodies (inhibition of enzyme activity and inhibition of enzyme uptake). Enzyme-linked immunosorbent assay (ELISA) was used to measure inhibition of rhGAA enzymatic activity in vitro and a cell-based assay was used to measure the inhibition of the uptake of rhGAA in normal fibroblast cells by flow cytometry.
Time Frame	End of study (up to Week 79)

Outcome Measure Data

Analysis Population Description

FAS population included all enrolled patients who signed informed consent and received at least 1 dose of alglucosidase alfa. Here, number of patients analyzed = patients with positive anti-rhGAA IgG antibody.

Arm/Group Title	Alglucosidase Alfa
Arm/Group Description:	Alglucosidase alfa (Myozyme®) 20 mg/kg IV infusion qow (or optionally 20 mg/kg IV infusion every week [qw]) beginning from Day 0 to a minimum of 18 months or if the patient was <6 months of age at the time of enrollment, until the patient was 2 years of age, along with methotrexate 0.4 mg/kg subcutaneously for 3 consecutive days qow beginning from Day 0 to Week 6 (9 doses) and rituximab 375 mg/m^2 (or 12.5 mg/kg for patients with body surface area less than or equal to 0.5 m^2) IV infusion qw beginning from Day -1 to Week 4 (4 doses) as per local prescribing information. An additional 4-week cycle of rituximab (up to 4 additional doses) and 6-week cycle of methotrexate (up to 9 additional doses) may have been administered within the first 6 months of the study as per local prescribing information.
Overall Number of Participants Analyzed	2
Measure Type: Number; Unit of Measure: participants
Inhibition of Enzyme Activity	0
Inhibition of Enzyme Uptake	0

3. Primary Outcome

Title	Number of Patients Who Survived at End of Study
Description	[Not Specified]
Time Frame	Baseline up to End of study (Week 79)

Outcome Measure Data

Analysis Population Description

FAS population included all enrolled patients who signed informed consent and received at least 1 dose of alglucosidase alfa.

Arm/Group Title	Alglucosidase Alfa
Arm/Group Description:	Alglucosidase alfa (Myozyme®) 20 mg/kg IV infusion qow (or optionally 20 mg/kg IV infusion every week [qw]) beginning from Day 0 to a minimum of 18 months or if the patient was <6 months of age at the time of enrollment, until the patient was 2 years of age, along with methotrexate 0.4 mg/kg subcutaneously for 3 consecutive days qow beginning from Day 0 to Week 6 (9 doses) and rituximab 375 mg/m^2 (or 12.5 mg/kg for patients with body surface area less than or equal to 0.5 m^2) IV infusion qw beginning from Day -1 to Week 4 (4 doses) as per local prescribing information. An additional 4-week cycle of rituximab (up to 4 additional doses) and 6-week cycle of methotrexate (up to 9 additional doses) may have been administered within the first 6 months of the study as per local prescribing information.
Overall Number of Participants Analyzed	4
Measure Type: Number; Unit of Measure: participants
	2

4. Primary Outcome

Title	Number of Patients With Normal/Abnormal Left Ventricular Mass (LVM) Z-Score and LVM Index at End of Study
Description	LVM Z-score and LVM index were assessed by ECHO. LVM Z-Score provides an indicator of degree of standard deviations from the mean in a normal distribution. Negative values indicate a smaller LVM than mean and values higher than 0 indicate a larger LVM than the mean. The normal range for LVM Z-Score is -2 to 2. Values <-2 or >2 indicate abnormal LVM Z-Score. LVM index is an index value derived by normalizing LVM by body surface area. LVM index provides evidence of cardiomyopathy. LVM index values <65 gram per meter^2 (g/m^2) were considered as normal and LVM index values >=65 g/m^2 were considered as abnormal. End of study refers to the last post baseline observation during study period (up to Week 79).
Time Frame	End of study (up to Week 79 or early termination)

Outcome Measure Data

Analysis Population Description

FAS population included all enrolled patients who signed informed consent and received at least 1 dose of alglucosidase alfa.

Arm/Group Title	Alglucosidase Alfa
Arm/Group Description:	Alglucosidase alfa (Myozyme®) 20 mg/kg IV infusion qow (or optionally 20 mg/kg IV infusion every week [qw]) beginning from Day 0 to a minimum of 18 months or if the patient was <6 months of age at the time of enrollment, until the patient was 2 years of age, along with methotrexate 0.4 mg/kg subcutaneously for 3 consecutive days qow beginning from Day 0 to Week 6 (9 doses) and rituximab 375 mg/m^2 (or 12.5 mg/kg for patients with body surface area less than or equal to 0.5 m^2) IV infusion qw beginning from Day -1 to Week 4 (4 doses) as per local prescribing information. An additional 4-week cycle of rituximab (up to 4 additional doses) and 6-week cycle of methotrexate (up to 9 additional doses) may have been administered within the first 6 months of the study as per local prescribing information.
Overall Number of Participants Analyzed	4
Measure Type: Number; Unit of Measure: participants
LVM Z-score: Normal	3
LVM Z-score: Abnormal	1
LVM index: Normal	2
LVM index: Abnormal	2

5. Primary Outcome

Title	Number of Patients With Ventilator Use at End of Study
Description	Number of patients who had ventilator support at end of study was reported. End of study refers to the last post baseline observation during study period (up to Week 79).
Time Frame	End of study (up to Week 79 or early termination)

Outcome Measure Data

Analysis Population Description

FAS population included all enrolled patients who signed informed consent and received at least 1 dose of alglucosidase alfa.

Arm/Group Title	Alglucosidase Alfa
Arm/Group Description:	Alglucosidase alfa (Myozyme®) 20 mg/kg IV infusion qow (or optionally 20 mg/kg IV infusion every week [qw]) beginning from Day 0 to a minimum of 18 months or if the patient was <6 months of age at the time of enrollment, until the patient was 2 years of age, along with methotrexate 0.4 mg/kg subcutaneously for 3 consecutive days qow beginning from Day 0 to Week 6 (9 doses) and rituximab 375 mg/m^2 (or 12.5 mg/kg for patients with body surface area less than or equal to 0.5 m^2) IV infusion qw beginning from Day -1 to Week 4 (4 doses) as per local prescribing information. An additional 4-week cycle of rituximab (up to 4 additional doses) and 6-week cycle of methotrexate (up to 9 additional doses) may have been administered within the first 6 months of the study as per local prescribing information.
Overall Number of Participants Analyzed	4
Measure Type: Number; Unit of Measure: participants
Yes	3
No	1

6. Primary Outcome

Title	Gross Motor Disability Assessed by Gross Motor Function Measure-88 (GMFM-88) at End of Study
Description	GMFM-88 is an 88-item measure to detect gross motor function. It consists of 5 categories: lying and rolling; sitting; crawling and kneeling; standing; walking, running and jumping. Each item is scored on a 4-point Likert scale (0 = cannot do; 1 = initiates [<10% of the task]; 2 = partially completes [10% to <100% of the task]; 3 = task completion). The score for each dimension is expressed as a percentage of the maximum score for that dimension. Total score is obtained by adding the percentage scores for each dimension and dividing the sum by the total number of dimensions. Total score ranges from 0% to 100%, where higher scores indicate better motor functions. A total score of <7.5% demonstrates gross motor disability. End of study refers to the last post baseline observation during study period (up to Week 79).
Time Frame	End of study (up to Week 79 or early termination)

Outcome Measure Data

Analysis Population Description

FAS population included all enrolled patients who signed informed consent and received at least 1 dose of alglucosidase alfa. Here, numbers of patients analyzed = patients with end of study GMFM-88 assessment.

Arm/Group Title	Alglucosidase Alfa
Arm/Group Description:	Alglucosidase alfa (Myozyme®) 20 mg/kg IV infusion qow (or optionally 20 mg/kg IV infusion every week [qw]) beginning from Day 0 to a minimum of 18 months or if the patient was <6 months of age at the time of enrollment, until the patient was 2 years of age, along with methotrexate 0.4 mg/kg subcutaneously for 3 consecutive days qow beginning from Day 0 to Week 6 (9 doses) and rituximab 375 mg/m^2 (or 12.5 mg/kg for patients with body surface area less than or equal to 0.5 m^2) IV infusion qw beginning from Day -1 to Week 4 (4 doses) as per local prescribing information. An additional 4-week cycle of rituximab (up to 4 additional doses) and 6-week cycle of methotrexate (up to 9 additional doses) may have been administered within the first 6 months of the study as per local prescribing information.
Overall Number of Participants Analyzed	3
Median (Full Range); Unit of Measure: percentage of maximum total score
	8.24; (6.76 to 89.8)

7. Primary Outcome

Title	Motor Development Status Assessed by Alberta Infantile Motor Scale (AIMS) at End of Study
Description	AIMS is a 58-item reliable and valid measure of motor development for infants at risk for motor delay. It assesses infant movement in 4 positions (subscales): prone (reciprocal crawling); supine (moving hands to feet); sitting (sitting with arm support); and standing (pulls to stand). For each subscale, items were scored as "observed" or "not observed". Item in the observed range create a motor window. When scoring, subscale scores are calculated by giving the child credit (1 point) for observed items within the motor window in addition to being given credit (1 point) for all of the less mature items before motor window. AIMS total score was calculated by summing the scores for 58 items and ranged from 0 to 58, with higher score indicating more mature motor development. Score was then compared with age-equivalent peers from normative sample and equivalence level age (in months) is reported. End of study refers to the last post baseline observation during study period (up to Week 79).
Time Frame	End of study (up to Week 79 or early termination)

Outcome Measure Data

Analysis Population Description

FAS population included all enrolled patients who signed informed consent and received at least 1 dose of alglucosidase alfa. Here, numbers of patients analyzed = patients with end of study AIMS assessment.

Arm/Group Title	Alglucosidase Alfa
Arm/Group Description:	Alglucosidase alfa (Myozyme®) 20 mg/kg IV infusion qow (or optionally 20 mg/kg IV infusion every week [qw]) beginning from Day 0 to a minimum of 18 months or if the patient was <6 months of age at the time of enrollment, until the patient was 2 years of age, along with methotrexate 0.4 mg/kg subcutaneously for 3 consecutive days qow beginning from Day 0 to Week 6 (9 doses) and rituximab 375 mg/m^2 (or 12.5 mg/kg for patients with body surface area less than or equal to 0.5 m^2) IV infusion qw beginning from Day -1 to Week 4 (4 doses) as per local prescribing information. An additional 4-week cycle of rituximab (up to 4 additional doses) and 6-week cycle of methotrexate (up to 9 additional doses) may have been administered within the first 6 months of the study as per local prescribing information.
Overall Number of Participants Analyzed	3
Median (Full Range); Unit of Measure: months
	1.09; (1.0 to 14.5)

8. Primary Outcome

Title	Disability Index Assessed by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) at End of Study
Description	The Pompe PEDI is a disease specific version of the PEDI that was developed to assess functional capabilities and performance in children with Pompe disease from 2 months through adolescence. It consists of all items of the original PEDI (197 functional skill items in 3 domains: self-care; mobility; and social function) and additional items in the functional skills, mobility, and self-care domains to reflect clinically relevant functional skills for children with Pompe disease. Each domain consisted of 2 subdomains: functional skill performance and caregiver assistance scale. Norm-based scoring was developed for these additional items, and scoring algorithms for the PEDI have been adjusted to reflect additional normative data collected for the Pompe PEDI. Total score range for each domain (mean of subdomains) and subdomain ranges from 0 to 100, where higher score indicates high capability. End of study refers to the last post baseline observation during study period (up to Week 79).
Time Frame	End of study (up to Week 79 or early termination)

Outcome Measure Data

Analysis Population Description

FAS population included all enrolled patients who signed informed consent and received at least 1 dose of alglucosidase alfa. Here, number of patient analyzed = number of patients with end of study Pompe PEDI assessment and n = number of patients with end of study assessment of specified category.

Arm/Group Title	Alglucosidase Alfa
Arm/Group Description:	Alglucosidase alfa (Myozyme®) 20 mg/kg IV infusion qow (or optionally 20 mg/kg IV infusion every week [qw]) beginning from Day 0 to a minimum of 18 months or if the patient was <6 months of age at the time of enrollment, until the patient was 2 years of age, along with methotrexate 0.4 mg/kg subcutaneously for 3 consecutive days qow beginning from Day 0 to Week 6 (9 doses) and rituximab 375 mg/m^2 (or 12.5 mg/kg for patients with body surface area less than or equal to 0.5 m^2) IV infusion qw beginning from Day -1 to Week 4 (4 doses) as per local prescribing information. An additional 4-week cycle of rituximab (up to 4 additional doses) and 6-week cycle of methotrexate (up to 9 additional doses) may have been administered within the first 6 months of the study as per local prescribing information.
Overall Number of Participants Analyzed	3
Median (Full Range); Unit of Measure: units on a scale
Functional Skills: Mobility Score (n=3)	25.1; (23.2 to 56)
Functional Skills: Self-Care Score (n=3)	39.3; (37 to 55.2)
Functional Skills: Social Function Score (n=3)	46.2; (40.4 to 46.8)
Caregiver Assistance: Mobility Score (n=3)	20.3; (20.3 to 31.9)
Caregiver Assistance: Self-Care Score (n=2)	28.7; (20.1 to 37.2)
Caregiver Assistance: Social Function Score (n=3)	48.5; (20.4 to 53.1)

Adverse Events

Time Frame	First dose of study drug up to end of study (up to Week 79)
Adverse Event Reporting Description	In the event a single participant has experienced both serious and non-serious form of the same adverse event (AE), individual has been included in numerator of both AE tables. Analysis was performed on the safety population: all patients who received at least 1 dose of alglucosidase alfa. AEs are listed independent of relationship to treatment.
Arm/Group Title	Alglucosidase Alfa
Arm/Group Description	Alglucosidase alfa (Myozyme®) 20 mg/kg IV infusion qow (or optionally 20 mg/kg IV infusion every week [qw]) beginning from Day 0 to a minimum of 18 months or if the patient was <6 months of age at the time of enrollment, until the patient was 2 years of age, along with methotrexate 0.4 mg/kg subcutaneously for 3 consecutive days qow beginning from Day 0 to Week 6 (9 doses) and rituximab 375 mg/m^2 (or 12.5 mg/kg for patients with body surface area less than or equal to 0.5 m^2) IV infusion qw beginning from Day -1 to Week 4 (4 doses) as per local prescribing information. An additional 4-week cycle of rituximab (up to 4 additional doses) and 6-week cycle of methotrexate (up to 9 additional doses) may have been administered within the first 6 months of the study as per local prescribing information.
All-Cause Mortality
	Alglucosidase Alfa
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Alglucosidase Alfa
	Affected / at Risk (%)
Total	3/4 (75.00%)
Cardiac disorders
Arrhythmia † 1	1/4 (25.00%)
Bradycardia † 1	1/4 (25.00%)
Cardiac arrest † 1	1/4 (25.00%)
Cardiopulmonary failure † 1	1/4 (25.00%)
Ear and labyrinth disorders
Tympanic membrane disorder † 1	1/4 (25.00%)
General disorders
Disease progression † 1	1/4 (25.00%)
Pyrexia † 1	2/4 (50.00%)
Infections and infestations
Clostridium difficile colitis † 1	1/4 (25.00%)
Pneumonia † 1	1/4 (25.00%)
Serratia sepsis † 1	1/4 (25.00%)
Tracheitis † 1	1/4 (25.00%)
Injury, poisoning and procedural complications
Feeding tube complication † 1	1/4 (25.00%)
Torus fracture † 1	1/4 (25.00%)
Investigations
Pulse absent † 1	1/4 (25.00%)
Metabolism and nutrition disorders
Fluid imbalance † 1	1/4 (25.00%)
Musculoskeletal and connective tissue disorders
Muscle contracture † 1	1/4 (25.00%)
Respiratory, thoracic and mediastinal disorders
Apnoea † 1	1/4 (25.00%)
Dyspnoea † 1	1/4 (25.00%)
Hypoxia † 1	1/4 (25.00%)
Laryngeal stenosis † 1	1/4 (25.00%)
Respiratory distress † 1	2/4 (50.00%)
Vascular disorders
Vena cava thrombosis † 1	1/4 (25.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 15.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Alglucosidase Alfa
	Affected / at Risk (%)
Total	4/4 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	2/4 (50.00%)
Lymphadenopathy † 1	1/4 (25.00%)
Neutropenia † 1	1/4 (25.00%)
Cardiac disorders
Bradycardia † 1	2/4 (50.00%)
Cyanosis † 1	1/4 (25.00%)
Extrasystoles † 1	1/4 (25.00%)
Tachycardia † 1	2/4 (50.00%)
Ear and labyrinth disorders
Tympanic membrane disorder † 1	2/4 (50.00%)
Eye disorders
Conjunctivitis † 1	1/4 (25.00%)
Eyelid ptosis † 1	1/4 (25.00%)
Periorbital oedema † 1	1/4 (25.00%)
Gastrointestinal disorders
Anal sphincter atony † 1	1/4 (25.00%)
Anorectal disorder † 1	1/4 (25.00%)
Constipation † 1	2/4 (50.00%)
Diarrhoea † 1	3/4 (75.00%)
Duodenogastric reflux † 1	1/4 (25.00%)
Flatulence † 1	1/4 (25.00%)
Gastritis † 1	1/4 (25.00%)
Haematemesis † 1	1/4 (25.00%)
Haematochezia † 1	1/4 (25.00%)
Retching † 1	1/4 (25.00%)
Teething † 1	1/4 (25.00%)
Vomiting † 1	3/4 (75.00%)
General disorders
Catheter site discharge † 1	1/4 (25.00%)
Catheter site erosion † 1	1/4 (25.00%)
Catheter site erythema † 1	2/4 (50.00%)
Catheter site pruritus † 1	1/4 (25.00%)
Catheter site rash † 1	2/4 (50.00%)
Catheter site related reaction † 1	1/4 (25.00%)
Device dislocation † 1	1/4 (25.00%)
Device occlusion † 1	3/4 (75.00%)
Face oedema † 1	1/4 (25.00%)
Fatigue † 1	1/4 (25.00%)
Intentional medical device removal by patient † 1	2/4 (50.00%)
Medical device complication † 1	1/4 (25.00%)
Oedema peripheral † 1	2/4 (50.00%)
Pyrexia † 1	4/4 (100.00%)
Infections and infestations
Body tinea † 1	1/4 (25.00%)
Candidiasis † 1	1/4 (25.00%)
Catheter site cellulitis † 1	1/4 (25.00%)
Clostridium difficile colitis † 1	1/4 (25.00%)
Gastroenteritis † 1	1/4 (25.00%)
Impetigo † 1	1/4 (25.00%)
Oral candidiasis † 1	1/4 (25.00%)
Otitis media † 1	1/4 (25.00%)
Otitis media acute † 1	1/4 (25.00%)
Sepsis † 1	1/4 (25.00%)
Serratia infection † 1	1/4 (25.00%)
Tracheitis † 1	2/4 (50.00%)
Urinary tract infection enterococcal † 1	1/4 (25.00%)
Viral infection † 1	1/4 (25.00%)
Injury, poisoning and procedural complications
Burns second degree † 1	1/4 (25.00%)
Laceration † 1	1/4 (25.00%)
Lip injury † 1	1/4 (25.00%)
Medication error † 1	1/4 (25.00%)
Overdose † 1	1/4 (25.00%)
Procedural pain † 1	2/4 (50.00%)
Procedural site reaction † 1	1/4 (25.00%)
Spinal compression fracture † 1	1/4 (25.00%)
Torus fracture † 1	1/4 (25.00%)
Investigations
Alanine aminotransferase increased † 1	2/4 (50.00%)
Antibiotic resistant Staphylococcus test positive † 1	1/4 (25.00%)
Aspartate aminotransferase increased † 1	2/4 (50.00%)
Band neutrophil percentage increased † 1	1/4 (25.00%)
Blood chloride decreased † 1	1/4 (25.00%)
Blood creatine phosphokinase MB increased † 1	2/4 (50.00%)
Blood creatine phosphokinase increased † 1	1/4 (25.00%)
Blood culture positive † 1	1/4 (25.00%)
Blood immunoglobulin G increased † 1	2/4 (50.00%)
Blood iron decreased † 1	1/4 (25.00%)
Blood lactate dehydrogenase increased † 1	1/4 (25.00%)
Blood potassium decreased † 1	1/4 (25.00%)
Blood potassium increased † 1	1/4 (25.00%)
Blood pressure increased † 1	1/4 (25.00%)
Blood sodium decreased † 1	1/4 (25.00%)
Body temperature increased † 1	1/4 (25.00%)
Clostridium test positive † 1	1/4 (25.00%)
Eosinophil percentage increased † 1	1/4 (25.00%)
Heart rate decreased † 1	1/4 (25.00%)
Heart rate irregular † 1	1/4 (25.00%)
Lymphocyte percentage decreased † 1	2/4 (50.00%)
Moraxella test positive † 1	1/4 (25.00%)
Neutrophil count decreased † 1	1/4 (25.00%)
Neutrophil percentage increased † 1	1/4 (25.00%)
Occult blood positive † 1	2/4 (50.00%)
Oxygen saturation decreased † 1	2/4 (50.00%)
Protein total decreased † 1	1/4 (25.00%)
Respiratory rate decreased † 1	1/4 (25.00%)
Respiratory rate increased † 1	1/4 (25.00%)
Reticulocyte percentage increased † 1	1/4 (25.00%)
Specific gravity urine increased † 1	1/4 (25.00%)
Urinary hexose tetrasaccharide increased † 1	1/4 (25.00%)
Urine output decreased † 1	1/4 (25.00%)
Weight decreased † 1	1/4 (25.00%)
White blood cell count decreased † 1	1/4 (25.00%)
White blood cell count increased † 1	1/4 (25.00%)
Metabolism and nutrition disorders
Dehydration † 1	1/4 (25.00%)
Vitamin D deficiency † 1	2/4 (50.00%)
Musculoskeletal and connective tissue disorders
Muscle contracture † 1	1/4 (25.00%)
Muscle spasms † 1	1/4 (25.00%)
Osteopenia † 1	1/4 (25.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Fibroma † 1	1/4 (25.00%)
Nervous system disorders
Clonus † 1	1/4 (25.00%)
Tremor † 1	1/4 (25.00%)
Psychiatric disorders
Agitation † 1	1/4 (25.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	1/4 (25.00%)
Aspiration † 1	1/4 (25.00%)
Atelectasis † 1	2/4 (50.00%)
Bronchial secretion retention † 1	1/4 (25.00%)
Bronchospasm † 1	1/4 (25.00%)
Cough † 1	1/4 (25.00%)
Diaphragm muscle weakness † 1	1/4 (25.00%)
Diaphragmatic disorder † 1	1/4 (25.00%)
Dyspnoea † 1	1/4 (25.00%)
Increased bronchial secretion † 1	1/4 (25.00%)
Laryngeal stenosis † 1	1/4 (25.00%)
Pneumonia aspiration † 1	1/4 (25.00%)
Pneumothorax † 1	1/4 (25.00%)
Respiratory distress † 1	1/4 (25.00%)
Rhinitis allergic † 1	1/4 (25.00%)
Rhinorrhoea † 1	1/4 (25.00%)
Tachypnoea † 1	2/4 (50.00%)
Wheezing † 1	2/4 (50.00%)
Skin and subcutaneous tissue disorders
Dermatitis contact † 1	1/4 (25.00%)
Dermatitis diaper † 1	3/4 (75.00%)
Drug eruption † 1	1/4 (25.00%)
Eczema † 1	1/4 (25.00%)
Erythema † 1	2/4 (50.00%)
Excessive granulation tissue † 1	2/4 (50.00%)
Hair colour changes † 1	2/4 (50.00%)
Hyperhidrosis † 1	1/4 (25.00%)
Macule † 1	1/4 (25.00%)
Palmar-plantar erythrodysaesthesia syndrome † 1	1/4 (25.00%)
Papule † 1	1/4 (25.00%)
Rash † 1	3/4 (75.00%)
Rash erythematous † 1	1/4 (25.00%)
Rash macular † 1	1/4 (25.00%)
Rash papular † 1	1/4 (25.00%)
Red man syndrome † 1	1/4 (25.00%)
Skin exfoliation † 1	2/4 (50.00%)
Skin hyperpigmentation † 1	1/4 (25.00%)
Skin hypopigmentation † 1	1/4 (25.00%)
Skin irritation † 1	1/4 (25.00%)
Skin ulcer † 1	1/4 (25.00%)
Swelling face † 1	1/4 (25.00%)
Surgical and medical procedures
Gastrointestinal tube removal † 1	1/4 (25.00%)
Post procedural drainage † 1	2/4 (50.00%)
Vascular disorders
Flushing † 1	1/4 (25.00%)
Hypotension † 1	1/4 (25.00%)
Pallor † 1	1/4 (25.00%)
Vena cava thrombosis † 1	1/4 (25.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 15.1

Limitations and Caveats

Due to the small number of patients assessed in this study the results must be interpreted with caution.

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.

Results Point of Contact

Name/Title: Trial Transparency Team

Organization: Sanofi

EMail: Contact-us@sanofi.com

Responsible Party:	Sanofi ( Genzyme, a Sanofi Company )
ClinicalTrials.gov Identifier:	NCT00701129 History of Changes
Other Study ID Numbers:	AGLU03807; MSC12862 ( Other Identifier: Sanofi )
First Submitted:	June 17, 2008
First Posted:	June 19, 2008
Results First Submitted:	February 24, 2014
Results First Posted:	May 13, 2014
Last Update Posted:	May 13, 2014