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A Placebo-Controlled Study of Safety and Effectiveness of Myozyme (Alglucosidase Alfa) in Patients With Late-Onset Pompe Disease

Primary Purpose

Pompe Disease (Late-onset), Glycogen Storage Disease Type II (GSD-II), Acid Maltase Deficiency Disease

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
alglucosidase alfa
Placebo
Sponsored by
Genzyme, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pompe Disease (Late-onset) focused on measuring Glycogen Storage Disease Type II, GSD-II, Pompe Disease

Eligibility Criteria

8 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Patient must provide signed, informed consent prior to performing any study-related procedures. Patient must have a diagnosis of Pompe disease based on deficient endogenous GAA activity in cultured skin fibroblasts of less than or equal to 40% of the normal mean of the testing laboratory and 2 confirmed GAA gene mutations; Patient must be greater than or equal to 8 years of age at the time of enrollment; Patient must be able to ambulate 40 meters (approximately 130 feet) in 6 minutes on each test performed on two consecutive days (use of assistive devices such as a walker, cane, or crutches, is permitted); Patient must have an FVC of greater than or equal to 30% and < 80% predicted in the upright position; Patient must have a postural drop in FVC (liters) of at least 10% from the upright to the supine position; Patient must have proximal muscle weakness in the lower limbs based on unilateral QMT of the knee extensors defined as < 80% of the predicted value based on age, gender and body size Patient must be able to tolerate pulmonary function testing (PFT) and muscle testing in the supine position; Patient must have testable muscle in bilateral knee flexors and knee extensors, and testable muscle in bilateral elbow flexors and elbow extensors; Patient must be able to provide reproducible muscle and pulmonary function test results; Patient (and patient's legal guardian if patient is < 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 (urine) 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: Patient requires the use of invasive ventilatory support; Patient requires the use of noninvasive ventilatory support while awake and in an upright position; Patient has received enzyme replacement therapy with GAA from any source; Patient has used an investigational product within 30 days prior to study enrollment, or is currently enrolled in another study which involves clinical evaluations, unless prior approval is given by Genzyme; Patient has a major congenital anomaly, medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities;

Sites / Locations

  • Tower Hematology Oncology Medical Group
  • Children's National Medical Center
  • Washington University Medical Center
  • Mount Sinai School of Medicine
  • University of Pittsburgh, Dept. of Neurology
  • Groupe Hospitalier Pitie-Salpetriere
  • Sophia Children's Hospital, Erasmus MC
  • Erasmus Medical Centre Rotterdam

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

alglucosidase alfa

Placebo

Arm Description

Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks.

Intravenous (IV) infusions of placebo every other week (qow) for 78 weeks.

Outcomes

Primary Outcome Measures

Summary of Patients Reporting Treatment-Emergent Adverse Events
Overall safety summary of patients experiencing 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, i.e., alglucosidase alfa or placebo.
Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline
Mean distance walked gives an indication of functional endurance. The greater the distance, the greater the endurance. Mean values of distance walked in a six-minute walk test are offered for baseline, week 78 (or last available observation), and the mean change from baseline (at week 78 or last available post-baseline observation).
Percent of Predicted Forced Vital Capacity (FVC)
Forced vital capacity is a standard pulmonary function test used to quantify respiratory muscle weakness. Forced vital capacity (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%.
Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Area Under the Curve (AUC)
Area under the plasma concentration versus time curve from time zero (pre-dose) to 16 hours after the end of infusion. Blood sample time points were 0 (before the start of the infusion), 1 and 2 hours after the start of infusion, end of the infusion, and then 0.25, 0.5, 1, 2, 3, 4, 8, 12,and 16 hours after the end of the infusion (with a 5-minute window for time-points after the start of infusion). Pooled figures combine the values for the three timeframes.
Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Maximum Plasma Concentration(Cmax)
Maximum plasma concentration observed in blood samples taken at the following time points: 0 (before the start of the infusion), 1 and 2 hours after the start of infusion, end of the infusion, and then 0.25, 0.5, 1, 2, 3, 4, 8, 12,and 16 hours after the end of the infusion (with a 5-minute window for time-points after the start of infusion). Pooled figures combine the values for the three timeframes.
Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Time to Maximum Plasma Concentration(Tmax)
Time to maximum plasma concentration observed in blood samples taken at the following time points: 0 (before the start of the infusion), 1 and 2 hours after the start of infusion, end of the infusion, and then 0.25, 0.5, 1, 2, 3, 4, 8, 12,and 16 hours after the end of the infusion (with a 5-minute window for time-points after the start of infusion). Pooled figures combine the values for the three timeframes.

Secondary Outcome Measures

Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT)
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 is 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.
Health-related Quality of Life Survey Values Related to Physical Components as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey
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 Scores (PCS) report the four domains of physical functioning, role-physical, bodily pain, and general health. Higher scores are associated with better quality of life. All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible. The PCS scores are reported.

Full Information

First Posted
September 8, 2005
Last Updated
April 6, 2015
Sponsor
Genzyme, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT00158600
Brief Title
A Placebo-Controlled Study of Safety and Effectiveness of Myozyme (Alglucosidase Alfa) in Patients With Late-Onset Pompe Disease
Official Title
Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Efficacy and Pharmacokinetics of Myozyme in Patients With Late-Onset Pompe Disease.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
September 2005 (undefined)
Primary Completion Date
September 2007 (Actual)
Study Completion Date
September 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Genzyme, a Sanofi Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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 overall objective is to evaluate the safety, efficacy, and pharmacokinetics (PK) of alglucosidase alfa treatment in patients with late-onset Pompe disease as compared to placebo.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pompe Disease (Late-onset), Glycogen Storage Disease Type II (GSD-II), Acid Maltase Deficiency Disease, Glycogenosis 2
Keywords
Glycogen Storage Disease Type II, GSD-II, Pompe Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
90 (Actual)

8. Arms, Groups, and Interventions

Arm Title
alglucosidase alfa
Arm Type
Active Comparator
Arm Description
Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Intravenous (IV) infusions of placebo every other week (qow) for 78 weeks.
Intervention Type
Biological
Intervention Name(s)
alglucosidase alfa
Other Intervention Name(s)
Myozyme, Lumizyme
Intervention Description
IV infusion of 20mg/kg; qow for 78 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo Comparator; qow for 78 weeks.
Primary Outcome Measure Information:
Title
Summary of Patients Reporting Treatment-Emergent Adverse Events
Description
Overall safety summary of patients experiencing 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, i.e., alglucosidase alfa or placebo.
Time Frame
weeks 0-78
Title
Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline
Description
Mean distance walked gives an indication of functional endurance. The greater the distance, the greater the endurance. Mean values of distance walked in a six-minute walk test are offered for baseline, week 78 (or last available observation), and the mean change from baseline (at week 78 or last available post-baseline observation).
Time Frame
weeks 0, 78
Title
Percent of Predicted Forced Vital Capacity (FVC)
Description
Forced vital capacity is a standard pulmonary function test used to quantify respiratory muscle weakness. Forced vital capacity (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 Frame
weeks 0, 78
Title
Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Area Under the Curve (AUC)
Description
Area under the plasma concentration versus time curve from time zero (pre-dose) to 16 hours after the end of infusion. Blood sample time points were 0 (before the start of the infusion), 1 and 2 hours after the start of infusion, end of the infusion, and then 0.25, 0.5, 1, 2, 3, 4, 8, 12,and 16 hours after the end of the infusion (with a 5-minute window for time-points after the start of infusion). Pooled figures combine the values for the three timeframes.
Time Frame
weeks 0, 12 and 52
Title
Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Maximum Plasma Concentration(Cmax)
Description
Maximum plasma concentration observed in blood samples taken at the following time points: 0 (before the start of the infusion), 1 and 2 hours after the start of infusion, end of the infusion, and then 0.25, 0.5, 1, 2, 3, 4, 8, 12,and 16 hours after the end of the infusion (with a 5-minute window for time-points after the start of infusion). Pooled figures combine the values for the three timeframes.
Time Frame
weeks 0, 12, 52
Title
Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Time to Maximum Plasma Concentration(Tmax)
Description
Time to maximum plasma concentration observed in blood samples taken at the following time points: 0 (before the start of the infusion), 1 and 2 hours after the start of infusion, end of the infusion, and then 0.25, 0.5, 1, 2, 3, 4, 8, 12,and 16 hours after the end of the infusion (with a 5-minute window for time-points after the start of infusion). Pooled figures combine the values for the three timeframes.
Time Frame
weeks 0, 12, 52
Secondary Outcome Measure Information:
Title
Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT)
Description
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 is 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.
Time Frame
weeks 0, 78
Title
Health-related Quality of Life Survey Values Related to Physical Components as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey
Description
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 Scores (PCS) report the four domains of physical functioning, role-physical, bodily pain, and general health. Higher scores are associated with better quality of life. All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible. The PCS scores are reported.
Time Frame
weeks 0, 78

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patient must provide signed, informed consent prior to performing any study-related procedures. Patient must have a diagnosis of Pompe disease based on deficient endogenous GAA activity in cultured skin fibroblasts of less than or equal to 40% of the normal mean of the testing laboratory and 2 confirmed GAA gene mutations; Patient must be greater than or equal to 8 years of age at the time of enrollment; Patient must be able to ambulate 40 meters (approximately 130 feet) in 6 minutes on each test performed on two consecutive days (use of assistive devices such as a walker, cane, or crutches, is permitted); Patient must have an FVC of greater than or equal to 30% and < 80% predicted in the upright position; Patient must have a postural drop in FVC (liters) of at least 10% from the upright to the supine position; Patient must have proximal muscle weakness in the lower limbs based on unilateral QMT of the knee extensors defined as < 80% of the predicted value based on age, gender and body size Patient must be able to tolerate pulmonary function testing (PFT) and muscle testing in the supine position; Patient must have testable muscle in bilateral knee flexors and knee extensors, and testable muscle in bilateral elbow flexors and elbow extensors; Patient must be able to provide reproducible muscle and pulmonary function test results; Patient (and patient's legal guardian if patient is < 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 (urine) 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: Patient requires the use of invasive ventilatory support; Patient requires the use of noninvasive ventilatory support while awake and in an upright position; Patient has received enzyme replacement therapy with GAA from any source; Patient has used an investigational product within 30 days prior to study enrollment, or is currently enrolled in another study which involves clinical evaluations, unless prior approval is given by Genzyme; Patient has a major congenital anomaly, medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities;
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Genzyme, a Sanofi Company
Official's Role
Study Director
Facility Information:
Facility Name
Tower Hematology Oncology Medical Group
City
Beverly Hills
State/Province
California
ZIP/Postal Code
90211
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Washington University Medical Center
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Mount Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
University of Pittsburgh, Dept. of Neurology
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Groupe Hospitalier Pitie-Salpetriere
City
Paris
ZIP/Postal Code
75651
Country
France
Facility Name
Sophia Children's Hospital, Erasmus MC
City
Rotterdam
ZIP/Postal Code
3000 CB
Country
Netherlands
Facility Name
Erasmus Medical Centre Rotterdam
City
Rotterdam
ZIP/Postal Code
3015 GD
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
21543987
Citation
Forsha D, Li JS, Smith PB, van der Ploeg AT, Kishnani P, Pasquali SK; Late-Onset Treatment Study Investigators. Cardiovascular abnormalities in late-onset Pompe disease and response to enzyme replacement therapy. Genet Med. 2011 Jul;13(7):625-31. doi: 10.1097/GIM.0b013e3182142966.
Results Reference
derived
PubMed Identifier
20393176
Citation
van der Ploeg AT, Clemens PR, Corzo D, Escolar DM, Florence J, Groeneveld GJ, Herson S, Kishnani PS, Laforet P, Lake SL, Lange DJ, Leshner RT, Mayhew JE, Morgan C, Nozaki K, Park DJ, Pestronk A, Rosenbloom B, Skrinar A, van Capelle CI, van der Beek NA, Wasserstein M, Zivkovic SA. A randomized study of alglucosidase alfa in late-onset Pompe's disease. N Engl J Med. 2010 Apr 15;362(15):1396-406. doi: 10.1056/NEJMoa0909859.
Results Reference
derived

Learn more about this trial

A Placebo-Controlled Study of Safety and Effectiveness of Myozyme (Alglucosidase Alfa) in Patients With Late-Onset Pompe Disease

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