PAPAYA: Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease

• Sponsor: Genzyme, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01410890
• Collaborator: (none)
• Enrollment: 21
• Locations: 12
• Arm: 1
• Actual Duration (Months): 72.6
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

• The primary objective of this study was to characterize the pharmacokinetics (PK) of alglucosidase alfa manufactured at the 4000 L scale in participants who had a confirmed diagnosis of Pompe disease.

• A secondary objective of this study was to evaluate and explore the relationship between anti-recombinant human acid alpha-glucosidase antibody titers and the PK of alglucosidase alfa.

Condition or Disease	Intervention/Treatment	Phase
Pompe Disease; Glycogen Storage Disease Type II (GSD II)	Biological: alglucosidase alfa	Phase 4

Detailed Description

The total study duration per participant was 4 to 8 weeks that consisted of a screening period (from 2 days to 4 weeks), treatment visit (1 day), and a follow up call (greater than or equal to 30 days). Two participants enrolled prior to protocol amendment 2 (dated 17 December 2015), which changed the study to single-dose, and were treated for 26 weeks, with a 4-week follow up.

Study Design

• Study Type: Interventional
• Actual Enrollment: 21 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase 3/4 Prospective Study to Characterize the Pharmacokinetics of Alglucosidase Alfa in Patients With Pompe Disease
• Actual Study Start Date: Nov 3, 2014
• Actual Primary Completion Date: Nov 20, 2020
• Actual Study Completion Date: Nov 20, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Alglucosidase alfa Participants received intravenous (IV) infusion of Alglucosidase alfa 20 milligrams per kilogram (mg/kg) body weight on Day 1. Infusion was administered at an initial rate of approximately 1 milligram per kilogram per hour (mg/kg/hr) with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of infusion-associated reactions (IARs), until a maximum rate of approximately 7 mg/kg/hr was reached.

Biological: alglucosidase alfa; Intravenous (IV) infusion of 20mg/kg body weight every other week (qow); Other Names: Lumizyme

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Alglucosidase Alfa [Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1]

   Cmax was defined as maximum observed plasma concentration.

2. Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alglucosidase Alfa [Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1]

   Tmax was defined as time to reach maximum observed plasma concentration.

3. Pharmacokinetics: Area Under the Plasma Concentration-Time Curve (AUC) of Alglucosidase Alfa [Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1]

   AUC was defined as area under the plasma concentration-time curve from time 0 to 24 hours post-dose.

4. Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Alglucosidase Alfa [Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1]

   AUC0-last was defined as area under the concentration-time curve from time 0 to the time of the last quantifiable concentration.

5. Pharmacokinetics: Terminal Elimination Half-life (T1/2) of Alglucosidase Alfa [Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1]

   T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.

6. Pharmacokinetics: Total Systemic Clearance (CL) of Alglucosidase Alfa [Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1]

   CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

7. Pharmacokinetics: Volume of Distribution at Steady State (Vss) of Alglucosidase Alfa [Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1]

   Volume of distribution (Vd) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is the apparent volume of distribution at steady-state.

Secondary Outcome Measures

1. Pharmacokinetics: Maximum Observed Plasma Concentration of Alglucosidase Alfa in Anti-Recombinant Human Acid Alpha-Glucosidase Antibody Positive and Negative Participants [Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1]

   Cmax was defined as maximum observed plasma concentration.

2. Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration in Anti-rhGAA Antibody Positive and Negative Participants [Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1]

   Tmax was defined as time to reach maximum observed plasma concentration.

3. Pharmacokinetics: Terminal Elimination Half-life of Alglucosidase Alfa in Anti-rhGAA Antibody Positive and Negative Participants [Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1]

   T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.

4. Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alglucosidase Alfa in Anti-rhGAA Antibody Positive and Negative Participants [Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1]

   AUC0-last was defined as area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration.

5. Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 and Extrapolated to Infinite Time (AUC0-inf) in Anti-rhGAA Antibody Positive and Negative Participants [Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1]

   AUC0-inf was defined as area under the concentration-time curve from time 0 extrapolated to infinite time.

6. Pharmacokinetics: Total Systemic Clearance in Anti-rhGAA Antibody Positive and Negative Participants [Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1]

   CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

7. Pharmacokinetics: Volume of Distribution in Anti-rhGAA Antibody Positive and Negative Participants [Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1]

   Vd is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is the apparent volume of distribution at steady-state.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

A participant was to meet all of the following criteria to be eligible for this study:

• The participant and/or the participant's parent/legal guardian was willing and able to provide signed informed consent.

• The participant had a confirmed acid alpha-glucosidase (GAA) enzyme deficiency from skin, blood, or muscle tissue and/or 2 confirmed GAA gene mutations.

• Infant and toddler Pompe disease participants could be included in the study only under condition (minimal body weight) that the trial-related blood loss (including any losses in the maneuver) would not exceed 3 percent (%) of the total blood volume during a period of 4 weeks and would not exceed 1 % at any single time.

• The participant, if female and of childbearing potential, must have had a negative pregnancy test (urine beta-human chorionic gonadotropin) at screening. Note: All female participants of childbearing potential and sexually mature males must have agreed to use a medically accepted method of contraception throughout the study.

• For participants previously treated with alglucosidase alfa the participant had received alglucosidase alfa for at least 6 months.

Exclusion Criteria:

A participant who met any of the following criteria was excluded from this study:

• The participant was participating in another clinical study using an investigational product.

• The participant, in the opinion of the Investigator, was unable to adhere to the requirements of the study.

The above information was 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 840008	Valhalla	New York	United States	10595
2	Investigational Site Number 840007	Cincinnati	Ohio	United States	45219
3	Investigational Site Number 840005	Salt Lake City	Utah	United States	84108
4	Investigational Site Number 840003	Fairfax	Virginia	United States	22030
5	Investigational Site Number 1028	Sofia		Bulgaria	1113
6	Investigational Site Number 356001	New Delhi		India	110 029
7	Investigational Site Number 356002	Vellore		India	632004
8	Investigational Site Number 643001	Moscow		Russian Federation	125367
9	Investigational Site Number 643002	Moscow		Russian Federation	125412
10	Investigational Site Number 804001	Kiev		Ukraine	01135
11	Investigational Site Number 826003	Birmingham		United Kingdom	B4 6NH
12	Investigational Site Number 826002	Salford		United Kingdom	M6 8HD

Sponsors and Collaborators

• Genzyme, a Sanofi Company

Investigators

• Study Director: Medical Monitor, Genzyme, a Sanofi Company

Study Documents (Full-Text)

• Study Protocol - Jul 18, 2016
• Statistical Analysis Plan - Dec 23, 2016

More Information

Publications

None provided.

• Responsible Party: Genzyme, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01410890
• Other Study ID Numbers: AGLU07710; 2010-022231-11; MSC12790
• First Posted: Aug 5, 2011
• Last Update Posted: Mar 28, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Glycogen Storage Disease Type II; Glycogen Storage Disease

Study Results

Participant Flow

Recruitment Details	The study was conducted at 12 sites in 6 countries. A total of 27 participants were screened between 03-Nov-2014 and 23-Sep-2020, of whom 6 participants were screen failures and 21 participants were enrolled in the study.
Pre-assignment Detail	Out of 21 participants, 1 participant signed the informed consent, but due to health status did not continue in the study to the treatment visit.

Arm/Group Title	Alglucosidase Alfa: <18 Years	Alglucosidase Alfa: >=18 Years
Arm/Group Description	Participants with less than (<) 18 years of age received intravenous (IV) infusion of Alglucosidase alfa 20 milligram per kilogram (mg/kg) body weight on Day 1. Infusion was administered at an initial rate of approximately 1 milligrams per kilogram per hour (mg/kg/hr) with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of infusion-associated reactions (IARs), until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with greater than or equal to (>=) 18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
Period Title: Overall Study
STARTED	10	11
Treated	10	10
COMPLETED	10	10
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Alglucosidase Alfa: <18 Years	Alglucosidase Alfa: >=18 Years	Total
Arm/Group Description	Participants with <18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with >=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Total of all reporting groups
Overall Participants	10	10	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	5.1 (3.95)	41.8 (12.44)	23.4 (20.86)
Sex: Female, Male (Count of Participants)
Female	5 50%	2 20%	7 35%
Male	5 50%	8 80%	13 65%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 10%	1 10%	2 10%
Not Hispanic or Latino	6 60%	8 80%	14 70%
Unknown or Not Reported	3 30%	1 10%	4 20%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 30%	1 10%	4 20%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	5 50%	9 90%	14 70%
More than one race	2 20%	0 0%	2 10%
Unknown or Not Reported	0 0%	0 0%	0 0%
Anti-Recombinant Human Acid Alpha-Glucosidase (rhGAA) Immunoglobulin G (IgG) Antibody Status (Count of Participants)
Positive	3 30%	4 40%	7 35%
Negative	6 60%	6 60%	12 60%
Missing	1 10%	0 0%	1 5%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Alglucosidase Alfa
Description	Cmax was defined as maximum observed plasma concentration.
Time Frame	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on all participants who received any amount of alglucosidase alfa.

Arm/Group Title	Alglucosidase Alfa: <18 Years	Alglucosidase Alfa: >=18 Years
Arm/Group Description	Participants with <18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with >=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
Measure Participants	10	10
Mean (Standard Deviation) [nanograms per milliliter (ng/mL)]	204000 (94600)	307000 (143000)

2. Primary Outcome

Title	Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Alglucosidase Alfa
Description	Tmax was defined as time to reach maximum observed plasma concentration.
Time Frame	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on all participants who received any amount of alglucosidase alfa.

Arm/Group Title	Alglucosidase Alfa: <18 Years	Alglucosidase Alfa: >=18 Years
Arm/Group Description	Participants with <18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with >=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
Measure Participants	10	10
Median (Full Range) [hours]	4.23	3.85

3. Primary Outcome

Title	Pharmacokinetics: Area Under the Plasma Concentration-Time Curve (AUC) of Alglucosidase Alfa
Description	AUC was defined as area under the plasma concentration-time curve from time 0 to 24 hours post-dose.
Time Frame	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on all participants who received any amount of alglucosidase alfa.

Arm/Group Title	Alglucosidase Alfa: <18 Years	Alglucosidase Alfa: >=18 Years
Arm/Group Description	Participants with <18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with >=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
Measure Participants	10	10
Mean (Standard Deviation) [hours per nanograms per milliliter]	1110000 (753000)	1890000 (969000)

4. Primary Outcome

Title	Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC0-last) of Alglucosidase Alfa
Description	AUC0-last was defined as area under the concentration-time curve from time 0 to the time of the last quantifiable concentration.
Time Frame	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on all participants who received any amount of alglucosidase alfa.

Arm/Group Title	Alglucosidase Alfa: <18 Years	Alglucosidase Alfa: >=18 Years
Arm/Group Description	Participants with <18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with >=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
Measure Participants	10	10
Mean (Standard Deviation) [hours per nanograms per milliliter]	1040000 (590000)	1840000 (901000)

5. Primary Outcome

Title	Pharmacokinetics: Terminal Elimination Half-life (T1/2) of Alglucosidase Alfa
Description	T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.
Time Frame	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on all participants who received any amount of alglucosidase alfa.

Arm/Group Title	Alglucosidase Alfa: <18 Years	Alglucosidase Alfa: >=18 Years
Arm/Group Description	Participants with <18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with >=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
Measure Participants	10	10
Mean (Standard Deviation) [hours]	5.43 (3.82)	3.84 (0.801)

6. Primary Outcome

Title	Pharmacokinetics: Total Systemic Clearance (CL) of Alglucosidase Alfa
Description	CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time Frame	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on all participants who received any amount of alglucosidase alfa.

Arm/Group Title	Alglucosidase Alfa: <18 Years	Alglucosidase Alfa: >=18 Years
Arm/Group Description	Participants with <18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with >=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
Measure Participants	10	10
Mean (Standard Deviation) [Liters per hour]	0.529 (0.613)	1.26 (1.24)

7. Primary Outcome

Title	Pharmacokinetics: Volume of Distribution at Steady State (Vss) of Alglucosidase Alfa
Description	Volume of distribution (Vd) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is the apparent volume of distribution at steady-state.
Time Frame	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on all participants who received any amount of alglucosidase alfa.

Arm/Group Title	Alglucosidase Alfa: <18 Years	Alglucosidase Alfa: >=18 Years
Arm/Group Description	Participants with <18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with >=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
Measure Participants	10	10
Mean (Standard Deviation) [Liters]	2.35 (2.02)	5.59 (3.72)

8. Secondary Outcome

Title	Pharmacokinetics: Maximum Observed Plasma Concentration of Alglucosidase Alfa in Anti-Recombinant Human Acid Alpha-Glucosidase Antibody Positive and Negative Participants
Description	Cmax was defined as maximum observed plasma concentration.
Time Frame	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Anti-rhGAA Antibody Negative Participants	Anti-rhGAA Antibody Positive Participants
Arm/Group Description	Participants with negative anti-rhGAA IgG antibody status at Baseline received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with positive anti-rhGAA IgG antibody status at Baseline received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
Measure Participants	12	7
Mean (Standard Deviation) [ng/mL]	256000 (121000)	262000 (160000)

9. Secondary Outcome

Title	Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration in Anti-rhGAA Antibody Positive and Negative Participants
Description	Tmax was defined as time to reach maximum observed plasma concentration.
Time Frame	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Anti-rhGAA Antibody Negative Participants	Anti-rhGAA Antibody Positive Participants
Arm/Group Description	Participants with negative anti-rhGAA IgG antibody status at Baseline received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with positive anti-rhGAA IgG antibody status at Baseline received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
Measure Participants	12	7
Median (Full Range) [hours]	3.94	4.33

10. Secondary Outcome

Title	Pharmacokinetics: Terminal Elimination Half-life of Alglucosidase Alfa in Anti-rhGAA Antibody Positive and Negative Participants
Description	T1/2 was defined as the time taken by drug to reduce to half of its initial plasma concentration.
Time Frame	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Anti-rhGAA Antibody Negative Participants	Anti-rhGAA Antibody Positive Participants
Arm/Group Description	Participants with negative anti-rhGAA IgG antibody status at Baseline received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with positive anti-rhGAA IgG antibody status at Baseline received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
Measure Participants	12	7
Mean (Standard Deviation) [hours]	4.68 (2.95)	4.79 (2.93)

11. Secondary Outcome

Title	Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alglucosidase Alfa in Anti-rhGAA Antibody Positive and Negative Participants
Description	AUC0-last was defined as area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration.
Time Frame	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Anti-rhGAA Antibody Negative Participants	Anti-rhGAA Antibody Positive Participants
Arm/Group Description	Participants with negative anti-rhGAA IgG antibody status at Baseline received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with positive anti-rhGAA IgG antibody status at Baseline received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
Measure Participants	12	7
Mean (Standard Deviation) [hours per nanograms per milliliter]	1410000 (865000)	1610000 (86800)

12. Secondary Outcome

Title	Pharmacokinetics: Area Under the Concentration-time Curve From Time 0 and Extrapolated to Infinite Time (AUC0-inf) in Anti-rhGAA Antibody Positive and Negative Participants
Description	AUC0-inf was defined as area under the concentration-time curve from time 0 extrapolated to infinite time.
Time Frame	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Anti-rhGAA Antibody Negative Participants	Anti-rhGAA Antibody Positive Participants
Arm/Group Description	Participants with negative anti-rhGAA IgG antibody status at Baseline received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with positive anti-rhGAA IgG antibody status at Baseline received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
Measure Participants	12	7
Mean (Standard Deviation) [hours per nanograms per milliliter]	1450000 (941000)	1700000 (985000)

13. Secondary Outcome

Title	Pharmacokinetics: Total Systemic Clearance in Anti-rhGAA Antibody Positive and Negative Participants
Description	CL of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.
Time Frame	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Anti-rhGAA Antibody Negative Participants	Anti-rhGAA Antibody Positive Participants
Arm/Group Description	Participants with negative anti-rhGAA IgG antibody status at Baseline received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with positive anti-rhGAA IgG antibody status at Baseline received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
Measure Participants	12	7
Mean (Standard Deviation) [Liters per hour]	0.765 (0.518)	1.21 (1.60)

14. Secondary Outcome

Title	Pharmacokinetics: Volume of Distribution in Anti-rhGAA Antibody Positive and Negative Participants
Description	Vd is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is the apparent volume of distribution at steady-state.
Time Frame	Pre-dose and at 1, 2, 4, 8, 12, and 24 hours Post-dose on Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Anti-rhGAA Antibody Negative Participants	Anti-rhGAA Antibody Positive Participants
Arm/Group Description	Participants with negative anti-rhGAA IgG antibody status at Baseline received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.	Participants with positive anti-rhGAA IgG antibody status at Baseline received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
Measure Participants	12	7
Mean (Standard Deviation) [Liters]	5.82 (6.49)	7.26 (9.16)

Adverse Events

Time Frame	All Adverse Events (AEs) were collected from signature of the informed consent form up to Week 4.
Adverse Event Reporting Description	Reported AEs and deaths were treatment-emergent (TEAEs) that developed/worsened in grade/became serious during 'TEAE period' (i.e., from signature of the informed consent form up to Week 4. Analysis was performed on FAS that included all participants who received any amount of alglucosidase alfa.
Arm/Group Title	Alglucosidase Alfa: <18 Years		Alglucosidase Alfa: >=18 Years
Arm/Group Description	Participants with <18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.		Participants with >=18 years of age received IV infusion of Alglucosidase alfa 20 mg/kg body weight on Day 1. Infusion was administered at an initial rate of approximately 1 mg/kg/hr with allowed rate increased of 2 mg/kg/hr every 30 minutes, if there were no signs of IARs, until a maximum rate of approximately 7 mg/kg/hr was reached.
All Cause Mortality
	Alglucosidase Alfa: <18 Years		Alglucosidase Alfa: >=18 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Serious Adverse Events
	Alglucosidase Alfa: <18 Years		Alglucosidase Alfa: >=18 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/10 (10%)		0/10 (0%)
Respiratory, thoracic and mediastinal disorders
Respiratory Distress	1/10 (10%)	1	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	Alglucosidase Alfa: <18 Years		Alglucosidase Alfa: >=18 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/10 (40%)		3/10 (30%)
General disorders
Fatigue	0/10 (0%)	0	1/10 (10%)	1
Pyrexia	1/10 (10%)	1	0/10 (0%)	0
Infections and infestations
Fungal Skin Infection	0/10 (0%)	0	1/10 (10%)	1
Nasopharyngitis	2/10 (20%)	2	0/10 (0%)	0
Rhinitis	1/10 (10%)	1	0/10 (0%)	0
Injury, poisoning and procedural complications
Fall	0/10 (0%)	0	1/10 (10%)	2
Investigations
Blood Pressure Increased	1/10 (10%)	1	0/10 (0%)	0
Body Temperature Increased	1/10 (10%)	1	0/10 (0%)	0
Musculoskeletal and connective tissue disorders
Osteoporosis	1/10 (10%)	1	0/10 (0%)	0
Pain In Extremity	0/10 (0%)	0	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Papule	1/10 (10%)	1	0/10 (0%)	0
Urticaria	2/10 (20%)	2	0/10 (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.