Clinical trial NCT00158600: 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
Overall status: COMPLETED
Phase: PHASE3
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
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2005-09-12
Enrollment: 90
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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;

Primary outcomes:
measure: Summary of Patients Reporting Treatment-Emergent Adverse Events
timeFrame: weeks 0-78
measure: Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline
timeFrame: weeks 0, 78
measure: Percent of Predicted Forced Vital Capacity (FVC)
timeFrame: weeks 0, 78
measure: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Area Under the Curve (AUC)
timeFrame: weeks 0, 12 and 52
measure: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Maximum Plasma Concentration(Cmax)
timeFrame: weeks 0, 12, 52
measure: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Time to Maximum Plasma Concentration(Tmax)
timeFrame: weeks 0, 12, 52
Secondary outcomes:
measure: Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT)
timeFrame: weeks 0, 78
measure: Health-related Quality of Life Survey Values Related to Physical Components as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey
timeFrame: weeks 0, 78
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Tower Hematology Oncology Medical Group
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: St. Louis
country: United States
facility: Washington University Medical Center
state: Missouri
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh, Dept. of Neurology
state: Pennsylvania
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Rotterdam
country: Netherlands
facility: Sophia Children's Hospital, Erasmus MC
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Centre Rotterdam
Study officials:
affiliation: Genzyme, a Sanofi Company
name: Medical Monitor
role: STUDY_DIRECTOR
References:
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.
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.