A Noninferiority Study of Alglucosidase Alfa Manufactured at the 160 L and 4000 L Scales in Treatment Naïve Patients With Infantile-Onset Pompe Disease

A Phase 3/4, Prospective, Multinational, Open-label, Noninferiority Study of Alglucosidase Alfa Manufactured at the 160 L and 4000 L Scales in Treatment Naïve Patients With Infantile-Onset Pompe Disease

A study to demonstrate comparable safety, efficacy, and pharmacokinetics (PK) of alglucosidase alfa manufactured at the 160 litre (L) and 4000 L scales in participants who had been diagnosed with infantile-onset Pompe disease. Participants were treated with alglucosidase alfa 160 L scale product in the United States (US) and 4000 L scale product in the regions outside the US.

Study Overview

• Status: Terminated
• Conditions: Glycogenosis 2; Glycogen Storage Disease Type II (GSD II); Acid Maltase Deficiency; Pompe Disease (Infantile-Onset)
• Intervention / Treatment: Biological: alglucosidase alfa; Biological: alglucosidase alfa

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Geiben, Germany
  • Mainz, Germany
• Taiwan
  • Taipei, Taiwan
• United States
  • Arkansas
    • Little Rock, Arkansas, United States
  • California
    • Oakland, California, United States
  • Florida
    • Gainsville, Florida, United States
  • Georgia
    • Decatur, Georgia, United States
  • Illinois
    • Chicago, Illinois, United States
  • Massachusetts
    • Cambridge, Massachusetts, United States
  • Michigan
    • Detroit, Michigan, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • New Jersey
    • New Brunswick, New Jersey, United States
  • New York
    • New York, New York, United States
  • North Carolina
    • Durham, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Texas
    • Fort Worth, Texas, United States
  • Washington
    • Seattle, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The participant's parent/legal guardian was willing and able to provide signed informed consent.
• The participant might be less than or equal to 12 months of age.
• The participant might have documented GAA enzyme deficiency from blood, skin, or muscle tissue.
• The participant might be naïve to treatment with alglucosidase alfa.

Exclusion Criteria:

• The participant was cross-reactive immunologic material negative.
• The participant required invasive ventilator support at the time of enrollment.
• The participant had decompensated clinical heart failure.
• The participant had a major congenital abnormality, excluding cardiac hypertrophy.
• The participant had a clinically significant organ disease (excluding the signs and symptoms of Pompe disease).
• The participant was currently receiving any investigational product.
• The participant was participating in another clinical study.
• The participant and/or the patient's parent/legal guardian was unable to adhere to the requirements of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alglucosidase Alfa 4000 L material (Non-US participants); Alglucosidase alfa 4000 L material for 52 weeks.	Biological: alglucosidase alfa; Intravenous (IV) infusion of alglucosidase alfa (4000 L material) 20 mg/kg every other week (QOW); Other Names: Lumizyme; Biological: alglucosidase alfa; IV infusion of alglucosidase alfa (160 L material) 20 mg/kg QOW.; Other Names: Myozyme
Active Comparator: Alglucosidase Alfa 160 L material (US participants); Alglucosidase alfa 160 L material for 52 weeks.	Biological: alglucosidase alfa; Intravenous (IV) infusion of alglucosidase alfa (4000 L material) 20 mg/kg every other week (QOW); Other Names: Lumizyme; Biological: alglucosidase alfa; IV infusion of alglucosidase alfa (160 L material) 20 mg/kg QOW.; Other Names: Myozyme

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Cardiac Function at Week 52	Cardiac function was measured by the left ventricular mass Z-score (LVM-Z). Z-Scores indicate the number of standard deviations (SD) from the mean in a normal distribution. A negative change from baseline indicates a decrease and positive change from baseline indicates an increase in LVM Z-score. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy.	Baseline, Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Estimated Probability of Survival		Up to Week 52
Number of Participants With Invasive Ventilator-Free Survival	Invasive ventilator-free survival was defined as the time during which the participant is alive and not invasively ventilated. Number of Participants with invasive ventilator-free survival were reported.	Up to Week 52
Change From Baseline in Motor Development Status at Week 52	Motor development status was assessed by the Gross Motor Function Measure - 88 Scale (GMFM-88) total percent scores. 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 was 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 was expressed as a percentage of the maximum score for that dimension. Total score ranges from 0% to 100%, where higher scores indicate better motor functions.	Baseline, Week 52

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: May 10, 2012
• First Submitted That Met QC Criteria: May 10, 2012
• First Posted (Estimate): May 14, 2012

Study Record Updates

• Last Update Posted (Estimate): January 18, 2016
• Last Update Submitted That Met QC Criteria: December 14, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease Type II; Glycogen Storage Disease
• Other Study ID Numbers: AGLU07510; 2011-005595-42 (EudraCT Number)