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

NCT00158600 | Completed Phase 3 Results DMC

• 2 other identifiers: AGLU027042005-002759-42
• Study Type: interventional
• Target: 90
• Locations: 3 countries
• Sites: 8

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.

Conditions

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

Outcome Measures

Primary Outcomes (6)

• 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.

  weeks 0-78

• 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).

  weeks 0, 78

• 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%.

  weeks 0, 78

• 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.

  weeks 0, 12 and 52

• 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.

  weeks 0, 12, 52

• 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.

  weeks 0, 12, 52

Secondary Outcomes (2)

• Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT)

  weeks 0, 78

• Health-related Quality of Life Survey Values Related to Physical Components as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey

  weeks 0, 78

Study Arms (2)

alglucosidase alfa

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

alglucosidase alfa BIOLOGICAL

IV infusion of 20mg/kg; qow for 78 weeks.

Also known as: Myozyme, Lumizyme

alglucosidase alfa

Placebo DRUG

Placebo Comparator; qow for 78 weeks.

Placebo

Eligibility Criteria

• Age: 8 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (8)

Tower Hematology Oncology Medical Group

Beverly Hills, California, 90211, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Washington University Medical Center

St Louis, Missouri, 63110, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

University of Pittsburgh, Dept. of Neurology

Pittsburgh, Pennsylvania, 15213, United States

Location

Groupe Hospitalier Pitie-Salpetriere

Paris, 75651, France

Location

Sophia Children's Hospital, Erasmus MC

Rotterdam, 3000 CB, Netherlands

Location

Erasmus Medical Centre Rotterdam

Rotterdam, 3015 GD, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 21543987 DERIVED

• 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.

  PMID: 20393176 DERIVED

MeSH Terms

Conditions

Glycogen Storage Disease Type II

Interventions

GAA protein, human

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Genzyme Medical Information
• Organization: Genzyme Corporation

800-745-4447

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Expanded Access: Yes

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Study Start: September 1, 2005
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2007
• Last Updated: April 28, 2015
• Results First Posted: July 23, 2010

Record last verified: 2015-04

Locations

US (5); NL (2); FR (1)