Clinical trial NCT00701129: An Exploratory Study of the Safety and Efficacy of Prophylactic Immunomodulatory Treatment in Myozyme-naive Cross-Reacting Immunologic Material (CRIM[-]) Patients With Infantile-Onset Pompe Disease
Official title: An Exploratory Study of the Safety and Efficacy of Prophylactic Immunomodulatory Treatment in Myozyme®-Naive, CRIM(-) Patients With Infantile-onset Pompe Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pompe Disease
Glycogen Storage Disease Type II
Keywords: Glycogenesis 2
Acid
Maltase
Deficiency
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2008-06-19
Enrollment: 4
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to evaluate the efficacy, clinical benefits and safety of a prophylactic immunomodulatory regimen given prior to first treatment with alglucosidase alfa (Myozyme®) in patients with infantile-onset Pompe disease.

The objectives were to assess the efficacy of a prophylactic immunomodulatory regimen given prior to first treatment with alglucosidase alfa, as assessed by anti-recombinant human acid alpha-glucosidase (anti-rhGAA) antibody titers, and antibodies that inhibit the activity and/or uptake of alglucosidase alfa; to evaluate the clinical benefit as measured by overall survival, ventilator-free survival, left ventricular mass index (LVMI), gross motor function and development, disability index and the incidence of adverse events (AEs), serious adverse events (SAEs), and clinical laboratory abnormalities.


Eligibility criteria: Inclusion Criteria:

* The patient's legal guardian(s) must have provided written informed consent prior to any study-related procedures being performed
* The patient must have had a clinical diagnosis of Pompe disease as defined by documented acid alpha-glucosidase (GAA) deficiency (deficient endogenous GAA activity) in skin fibroblasts, muscle, or blood, or 2 GAA mutations. Consent was also sought from the biological parent(s) for parental GAA mutational analysis, but was not a requirement for study eligibility
* The patient must have not received Myozyme® or any rhGAA therapies prior to enrollment in the study
* The patient must be CRIM negative via Western Blot analysis performed on skin fibroblasts or via 2 known CRIM negative mutations (in which case CRIM status was to be confirmed by Western Blot analysis after enrollment)
* The patient's legal guardian(s) must have the ability to comply with the clinical protocol

Exclusion Criteria:

* The patient had any medical condition that, in the opinion of the Investigator, could be exacerbated/precipitated by or interfere with the study regimen or assessments; such conditions may include but were not limited to human immunodeficiency virus, cancer, Hepatitis B, Hepatitis C, Cytomegalovirus, Herpes Simplex, John Cunningham (JC) virus, Parvovirus, or Epstein Barr virus or tuberculosis
* The patient had used any investigational product within 30 days prior to study enrollment
* The patient had or was required to have any live vaccination within 1 month prior to enrollment

Primary outcomes:
measure: Change From Baseline in Number of Patients With Anti-Recombinant Human Acid Alfa-glucosidase (Anti-rhGAA) Immunoglobulin G (IgG) Antibody at End of Study
timeFrame: Baseline, End of Study (up to Week 79 or early termination)
measure: Number of Patients With Recombinant Human Acid Alfa-glucosidase (rhGAA) Inhibitory Antibody at End of Study
timeFrame: End of study (up to Week 79)
measure: Number of Patients Who Survived at End of Study
timeFrame: Baseline up to End of study (Week 79)
measure: Number of Patients With Normal/Abnormal Left Ventricular Mass (LVM) Z-Score and LVM Index at End of Study
timeFrame: End of study (up to Week 79 or early termination)
measure: Number of Patients With Ventilator Use at End of Study
timeFrame: End of study (up to Week 79 or early termination)
measure: Gross Motor Disability Assessed by Gross Motor Function Measure-88 (GMFM-88) at End of Study
timeFrame: End of study (up to Week 79 or early termination)
measure: Motor Development Status Assessed by Alberta Infantile Motor Scale (AIMS) at End of Study
timeFrame: End of study (up to Week 79 or early termination)
measure: Disability Index Assessed by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) at End of Study
timeFrame: End of study (up to Week 79 or early termination)
Secondary outcomes:
Other outcomes:
Locations:
city: Louisville
country: United States
facility: Kosair Children's Hospital
state: Kentucky
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Genzyme Coorporation
name: Medical Monitor
role: STUDY_DIRECTOR
References: