A Placebo-Controlled Study of Safety and Effectiveness of Myozyme (Alglucosidase Alfa) in Patients With Late-Onset Pompe Disease
Condition: Pompe Disease (Late-onset); Glycogen Storage Disease Type II (GSD-II); Acid Maltase Deficiency Disease; Glycogenosis 2
MeSH terms: Glycogen Storage Disease Type II; Glycogen Storage Disease; Deficiency Diseases; Disease
Intervention: alglucosidase alfa; Placebo
Intervention description: IV infusion of 20mg/kg; qow for 78 weeks.; Placebo Comparator; qow for 78 weeks.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 90.0
Sex: All
Minimum age: 8 Years
Healthy volunteers: No
Keywords: Glycogen Storage Disease Type II; GSD-II; Pompe Disease

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;