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

This study has been completed.
Sponsor:
Information provided by:
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT00158600
First received: September 8, 2005
Last updated: June 24, 2010
Last verified: June 2010
  Purpose

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.


Condition Intervention Phase
Pompe Disease (Late-onset)
Glycogen Storage Disease Type II (GSD-II)
Acid Maltase Deficiency Disease
Glycogenosis 2
Biological: alglucosidase alfa
Drug: Placebo
Phase 3

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Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Efficacy and Pharmacokinetics of Myozyme in Patients With Late-Onset Pompe Disease.

Resource links provided by NLM:


Further study details as provided by Genzyme, a Sanofi Company:

Primary Outcome Measures:
  • Summary of Patients Reporting Treatment-Emergent Adverse Events [ Time Frame: weeks 0-78 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: weeks 0, 78 ] [ Designated as safety issue: No ]
    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) [ Time Frame: weeks 0, 78 ] [ Designated as safety issue: No ]
    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) [ Time Frame: weeks 0, 12 and 52 ] [ Designated as safety issue: No ]
    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) [ Time Frame: weeks 0, 12, 52 ] [ Designated as safety issue: No ]
    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 Frame: weeks 0, 12, 52 ] [ Designated as safety issue: No ]
    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) [ Time Frame: weeks 0, 78 ] [ Designated as safety issue: No ]
    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 [ Time Frame: weeks 0, 78 ] [ Designated as safety issue: No ]
    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.


Enrollment: 90
Study Start Date: September 2005
Study Completion Date: September 2007
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: alglucosidase alfa
Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks.
Biological: alglucosidase alfa
IV infusion of 20mg/kg; qow for 78 weeks.
Other Names:
  • Myozyme
  • alglucosidase alfa
  • Lumizyme
Placebo Comparator: Placebo
Intravenous (IV) infusions of placebo every other week (qow) for 78 weeks.
Drug: Placebo
Placebo Comparator; qow for 78 weeks.

  Eligibility

Ages Eligible for Study:   8 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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;
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00158600

Locations
United States, California
Tower Hematology Oncology Medical Group
Beverly Hills, California, United States, 90211
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Missouri
Washington University Medical Center
St. Louis, Missouri, United States, 63110
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
United States, Pennsylvania
University of Pittsburgh, Dept. of Neurology
Pittsburgh, Pennsylvania, United States, 15213
France
Groupe Hospitalier Pitie-Salpetriere
Paris, France, 75651
Netherlands
Erasmus Medical Centre Rotterdam
Rotterdam, Netherlands, 3015 GD
Sophia Children's Hospital, Erasmus MC
Rotterdam, Netherlands, 3000 CB
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided by Genzyme, a Sanofi Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier: NCT00158600     History of Changes
Other Study ID Numbers: AGLU02704, 2005-002759-42
Study First Received: September 8, 2005
Results First Received: June 24, 2010
Last Updated: June 24, 2010
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Netherlands: College ter Beoordeling van Geneesmiddelen Medicines Evaluation Board (CBGMEB)

Keywords provided by Genzyme, a Sanofi Company:
Glycogen Storage Disease Type II
GSD-II
Pompe Disease

Additional relevant MeSH terms:
Deficiency Diseases
Glycogen Storage Disease Type II
Glycogen Storage Disease
Metabolic Diseases
Malnutrition
Nutrition Disorders
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Carbohydrate Metabolism, Inborn Errors
Lysosomal Storage Diseases

ClinicalTrials.gov processed this record on April 23, 2014