Late-Onset Treatment Study Extension Protocol

An Open-Label Extension Study of Patients With Late-Onset Pompe Disease Who Were Previously Enrolled in Protocol AGLU02704

Pompe disease (also known as glycogen storage disease Type II) is caused by a deficiency of a critical enzyme in the body called acid alpha-glucosidase (GAA). Normally, GAA is used by the body's cells to break down glycogen (a stored form of sugar) within specialized structures called lysosomes. In patients with Pompe disease, an excessive amount of glycogen accumulates and is stored in various tissues, especially heart and skeletal muscle, which prevents their normal function. The objective of this extension study is to assess the long-term safety and efficacy of alglucosidase alfa treatment in patients with Late-Onset Pompe Disease who were previously treated under the placebo-controlled, double-blind study AGLU02704 (NCT00158600).

Study Overview

• Status: Completed
• Conditions: Glycogen Storage Disease Type II (GSD-II); Pompe Disease (Late-Onset); Glycogenesis Type II; Acid Maltase Deficiency (AMD)
• Intervention / Treatment: Biological: alglucosidase alfa

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 4

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • Westmead, Australia
• Canada
  • Alberta
    • Calgary, Alberta, Canada
  • Quebec
    • Sherbrooke, Quebec, Canada
• France
  • Paris, France
• Netherlands
  • Rotterdam, Netherlands
• United States
  • Alaska
    • Anchorage, Alaska, United States
  • Arizona
    • Phoenix, Arizona, United States
  • California
    • Beverly Hills, California, United States
    • San Diego, California, United States
  • District of Columbia
    • Washington, District of Columbia, United States
  • Florida
    • Coral Springs, Florida, United States
    • Gainesville, Florida, United States
    • Sarasota, Florida, United States
  • Illinois
    • Chicago, Illinois, United States
  • Kansas
    • Kansas City, Kansas, United States
  • Louisiana
    • New Orleans, Louisiana, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Nebraska
    • Omaha, Nebraska, United States
  • New York
    • New York, New York, United States
  • North Carolina
    • Durham, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
    • Toledo, Ohio, United States
  • Oklahoma
    • Tulsa, Oklahoma, United States
  • Oregon
    • Portland, Oregon, United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
    • Pittsburgh, Pennsylvania, United States
  • South Carolina
    • Greenville, South Carolina, United States
  • Texas
    • Dallas, Texas, United States
    • San Antonio, Texas, United States
  • Washington
    • Seattle, Washington, United States
  • Wisconsin
    • Green Bay, Wisconsin, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient must have completed protocol AGLU02704 (NCT00158600)
• Patient must provide signed, informed consent prior to performing any study-related procedures
• Patient (and patient's legal guardian if patient is under 18 years of age) must have the ability to comply with the clinical protocol
• A female patient of childbearing potential must have a negative pregnancy test at Baseline. (note: all female patients of childbearing potential and sexually mature males must use a medically accepted method of contraception throughout the study.)

Exclusion Criteria:

• The patient has a medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, would preclude treatment with alglucosidase alfa.

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/Alglucosidase Alfa; Participants who received alglucosidase alfa during the double-blind study and, if they completed the double-blind study, continued that treatment during the extension study. Participants received an intravenous (IV) infusion of 20 mg/kg of alglucosidase alfa every other week (qow) until their participation in both the AGLU02704 (NCT00158600) and AGLU03206 studies combined equaled a minimum of 104 weeks.	Biological: alglucosidase alfa; IV infusion of 20 mg/kg; every other week (qow); Other Names: Myozyme; Lumizyme
Experimental: Placebo/Alglucosidase Alfa; Participants given placebo during the double-blind study, completed the double-blind study (study AGLU02704, NCT00158600), and qualified to continue into the extension study on alglucosidase alfa. Participants received an intravenous (IV) infusion of 20 mg/kg of alglucosidase alfa every other week (qow) for up to 52 weeks. Only the alglucosidase alfa treatment experience is included in this extension study.	Biological: alglucosidase alfa; IV infusion of 20 mg/kg; every other week (qow); Other Names: Myozyme; Lumizyme

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Summary of Participants Reporting Treatment-Emergent Adverse Events For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)	The numbers of participants who experienced Adverse Events (AEs), Serious Adverse Events (SAEs), treatment-related AEs, and Infusion Associated Reactions (IARs). Summary is based on treatment-emergent AEs (TEAEs), defined as AEs that occurred following the initiation of study treatment with alglucosidase alfa. Participants with long-term exposure to alglucosidase alfa (those from the Alglucosidase Alfa/Alglucosidase Alfa treatment group) are included. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600).	Week 0 to 2.5 years
Baseline Values (Week 0) of Functional Endurance as Measured by Six-Minute Walk Test (6MWT) For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)	Six-Minute Walk Test (6MWT) measures the distance walked (in meters) in 6 minutes. A longer distance indicates greater endurance. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600).	Week 0
Change From Baseline (Week 0) in the Six-Minute Walk Test (6MWT) at Week 104 For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)	Six-Minute Walk Test (6MWT) measures the distance walked (in meters) in 6 minutes. A longer distance indicates greater endurance. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). Change is calculated as the value minus the baseline value.	Week 0, Week 104
Baseline Values (Week 0) for Percent Predicted Forced Vital Capacity (FVC) For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)	Forced vital capacity (FVC) is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted forced vital capacity is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) * 100%. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600).	Week 0
Change From Baseline (Week 0) in the Percent Predicted Forced Vital Capacity (FVC) at Week 104 For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)	Forced vital capacity (FVC) is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted forced vital capacity is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) * 100%. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). Change is calculated as the value minus the baseline value.	Week 0, Week 104

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Values (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)	Quantitative muscle testing (QMT) is a standardized system to measure muscle force production during maximal voluntary isometric contraction. QMT data were collected directly from sensors into laptop computers. Predicted normal values for QMT are based on a formula using sex, age and body mass index of a person, and are an estimate of healthy muscle force. Percent of predicted QMT = (observed value)/(predicted value) * 100%. The QMT Leg Score is the average of the bilateral means for percent predicted knee flexors and extensors. A value of 100% indicates 'normal' muscle strength.	Week 0
Change From Baseline (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) at Week 104 For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)	Quantitative muscle testing (QMT) is a standardized system to measure muscle force production during maximal voluntary isometric contraction. QMT data were collected directly from sensors into laptop computers. Predicted normal values for QMT are based on a formula using sex, age and body mass index of a person, and are an estimate of healthy muscle force. Percent of predicted QMT = (observed value)/(predicted value) * 100%. The QMT Leg Score is the average of the bilateral means for percent predicted knee flexors and extensors. A value of 100% indicates 'normal' muscle strength.	Week 0, Week 104
Baseline Values (Week 0) for Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)	The Medical Outcomes Study Short Form (MOS SF)-36 questionnaire consists of 36 items grouped into 8 domains designed to assess generic health-related quality of life in healthy and ill adult populations. Physical Component Score reports the four domains of physical functioning, role-physical, bodily pain, and general health and are standardized as Z-scores (scale of 0-100). Higher scores are associated with better quality of life. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600).	Week 0
Change From Baseline in Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Participants Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)	The Medical Outcomes Study Short Form (MOS SF)-36 questionnaire consists of 36 items grouped into 8 domains designed to assess generic health-related quality of life in healthy and ill adult populations. Physical Component Score reports the four domains of physical functioning, role-physical, bodily pain, and general health and is standardized as Z-scores (scale of 0-100). Higher scores are associated with better quality of life. Change is calculated as the value minus the baseline value. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600).	Week 0 , Week 104

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: March 30, 2007
• First Submitted That Met QC Criteria: March 30, 2007
• First Posted (Estimate): April 3, 2007

Study Record Updates

• Last Update Posted (Estimate): March 7, 2014
• Last Update Submitted That Met QC Criteria: February 4, 2014
• Last Verified: February 1, 2014

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: AGLU03206; 2006-003644-31 (EudraCT Number)