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Completed

NCT Number: 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

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.

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Key information

Conditions

Pompe Disease Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Carbohydrate Metabolism, Inborn Errors Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Glycogen Storage Disease Glycogen Storage Disease Type II Heartburn Lysosomal Storage Diseases Lysosomal Storage Diseases, Nervous System Metabolic Diseases Metabolism, Inborn Errors Nervous System Diseases Nutritional and Metabolic Diseases Pathological Conditions, Signs and Symptoms Signs and Symptoms Signs and Symptoms, Digestive

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Kosair Children's Hospital, Louisville, Kentucky, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

alglucosidase alfa

Biological

Administered as IV infusion.

Other names: Myozyme®

methotrexate

Drug

Administered subcutaneously.

Rituximab

Drug

Administered as IV infusion.

Primary outcomes

  1. Change From Baseline in Number of Patients With Anti-Recombinant Human Acid Alfa-glucosidase (Anti-rhGAA) Immunoglobulin G (IgG) Antibody at End of Study

    Time frame: Baseline, End of Study (up to Week 79 or early termination)

    Serum samples from patients were analyzed for the presence of anti-rhGAA IgG antibodies. End of study (EOS) refers to the last post baseline observation during study period (up to Week 79).

  2. Number of Patients With Recombinant Human Acid Alfa-glucosidase (rhGAA) Inhibitory Antibody at End of Study

    Time frame: End of study (up to Week 79)

    Patients with positive anti-rhGAA IgG antibody were assessed for the presence of inhibitory antibodies (inhibition of enzyme activity and inhibition of enzyme uptake). Enzyme-linked immunosorbent assay (ELISA) was used to measure inhibition of rhGAA enzymatic activity in vitro and a cell-based assay was used to measure the inhibition of the uptake of rhGAA in normal fibroblast cells by flow cytometry.

  3. Number of Patients Who Survived at End of Study

    Time frame: Baseline up to End of study (Week 79)

  4. Number of Patients With Normal/Abnormal Left Ventricular Mass (LVM) Z-Score and LVM Index at End of Study

    Time frame: End of study (up to Week 79 or early termination)

    LVM Z-score and LVM index were assessed by ECHO. LVM Z-Score provides an indicator of degree of standard deviations from the mean in a normal distribution. Negative values indicate a smaller LVM than mean and values higher than 0 indicate a larger LVM than the mean. The normal range for LVM Z-Score is -2 to 2. Values <-2 or >2 indicate abnormal LVM Z-Score. LVM index is an index value derived by normalizing LVM by body surface area. LVM index provides evidence of cardiomyopathy. LVM index values <65 gram per meter^2 (g/m^2) were considered as normal and LVM index values >=65 g/m^2 were considered as abnormal. End of study refers to the last post baseline observation during study period (up to Week 79).

  5. Number of Patients With Ventilator Use at End of Study

    Time frame: End of study (up to Week 79 or early termination)

    Number of patients who had ventilator support at end of study was reported. End of study refers to the last post baseline observation during study period (up to Week 79).

  6. Gross Motor Disability Assessed by Gross Motor Function Measure-88 (GMFM-88) at End of Study

    Time frame: End of study (up to Week 79 or early termination)

    GMFM-88 is an 88-item measure to detect gross motor function. It consists of 5 categories: lying and rolling; sitting; crawling and kneeling; standing; walking, running and jumping. Each item is scored on a 4-point Likert scale (0 = cannot do; 1 = initiates [<10% of the task]; 2 = partially completes [10% to <100% of the task]; 3 = task completion). The score for each dimension is expressed as a percentage of the maximum score for that dimension. Total score is obtained by adding the percentage scores for each dimension and dividing the sum by the total number of dimensions. Total score ranges from 0% to 100%, where higher scores indicate better motor functions. A total score of <7.5% demonstrates gross motor disability. End of study refers to the last post baseline observation during study period (up to Week 79).

  7. Motor Development Status Assessed by Alberta Infantile Motor Scale (AIMS) at End of Study

    Time frame: End of study (up to Week 79 or early termination)

    AIMS is a 58-item reliable and valid measure of motor development for infants at risk for motor delay. It assesses infant movement in 4 positions (subscales): prone (reciprocal crawling); supine (moving hands to feet); sitting (sitting with arm support); and standing (pulls to stand). For each subscale, items were scored as "observed" or "not observed". Item in the observed range create a motor window. When scoring, subscale scores are calculated by giving the child credit (1 point) for observed items within the motor window in addition to being given credit (1 point) for all of the less mature items before motor window. AIMS total score was calculated by summing the scores for 58 items and ranged from 0 to 58, with higher score indicating more mature motor development. Score was then compared with age-equivalent peers from normative sample and equivalence level age (in months) is reported. End of study refers to the last post baseline observation during study period (up to Week 79).

  8. Disability Index Assessed by the Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) at End of Study

    Time frame: End of study (up to Week 79 or early termination)

    The Pompe PEDI is a disease specific version of the PEDI that was developed to assess functional capabilities and performance in children with Pompe disease from 2 months through adolescence. It consists of all items of the original PEDI (197 functional skill items in 3 domains: self-care; mobility; and social function) and additional items in the functional skills, mobility, and self-care domains to reflect clinically relevant functional skills for children with Pompe disease. Each domain consisted of 2 subdomains: functional skill performance and caregiver assistance scale. Norm-based scoring was developed for these additional items, and scoring algorithms for the PEDI have been adjusted to reflect additional normative data collected for the Pompe PEDI. Total score range for each domain (mean of subdomains) and subdomain ranges from 0 to 100, where higher score indicates high capability. End of study refers to the last post baseline observation during study period (up to Week 79).

Sponsors and collaborators

Lead sponsor

Genzyme, a Sanofi Company

Industry

Registry information

Official study title

An Exploratory Study of the Safety and Efficacy of Prophylactic Immunomodulatory Treatment in Myozyme®-Naive, CRIM(-) Patients With Infantile-onset Pompe Disease

Important dates

Study start
2009
Primary completion
2013
Study completion
2013
First posted
Jun 19, 2008
Registry last updated
May 13, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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