Growth and Development Study of Alglucosidase Alfa

A Long-term Study to Evaluate Growth and Development Outcomes in Patients With Infantile-Onset Pompe Disease Who Are Receiving Alglucosidase Alfa

Pompe disease (also known as glycogen storage disease Type II) is a rare autosomal recessive metabolic muscle disease caused by the deficiency of acid α glucosidase (GAA), an enzyme that degrades lysosomal glycogen. As opposed to the exclusively cytoplasmic accumulation of glycogen that occurs in other glycogen storage disorders, Pompe disease is characterized by organelle bound (lysosomal) and extra-lysosomal accumulation of glycogen in many body tissues, ultimately leading to multisystemic pathology. The overall objective of this study was to evaluate the long-term growth and development of participants with infantile-onset Pompe disease with alglucosidase alfa before 1 year of age. Participants were to be followed for a 10-year period.

Study Overview

• Status: Completed
• Conditions: Glycogen Storage Disease Type II (GSD-II); Acid Maltase Deficiency Disease; Pompe Disease
• Intervention / Treatment: Biological: alglucosidase alfa

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States
  • Georgia
    • Decatur, Georgia, United States
  • Michigan
    • Detroit, Michigan, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The participant or participant's legal guardian must have provided signed, informed consent prior to performing any study-related procedures.
• The participant must have had a confirmed diagnosis of Pompe disease as determined by deficient endogenous GAA activity or GAA mutation analysis.
• The participant must be less than (<) 1 year of age at time of study enrollment (and received alglucosidase alfa treatment before 1 year of age), or the participant must be between 1 year and 24 months of age and must have had initiated alglucosidase alfa treatment prior to turning 1 year of age.

Exclusion Criteria:

• The participant was participating in another clinical study using alglucosidase alfa or any investigational therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Alglucosidase Alfa; Participants received alglucosidase alfa 20 milligrams per kilogram (mg/kg) body weight as intravenous infusion every 2 weeks and were followed for 10 years or up to discontinuation from study treatment due to any reason.	Biological: alglucosidase alfa; Dose: 20 mg/kg every 2 weeks; Route of administration: Intravenous infusion; Other Names: Myozyme®; Lumizyme®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recumbent Height/Length of Participants in Centimeters (cm)	Height/Length of Participants was measured in centimeters. Week is denoted as Wk in time frame section.	Participants 1-12:Baseline, Participant1: Wk 52, Participant2: Wk82, Participants 3-4: Wk208, Participant5: Wk12, Participant6: Wk365, Participant7: Wk64, Participant8:Wk156, Participant9:Wk364, Participant10:Wk52, Participant11:Wk156, Participant12:Wk520
Body Weight of Participants in Kilograms (kg)	Body Weight of Participants was measured in Kilograms (kg). Week is denoted as Wk in time frame section.	Participant1-12:Baseline, Participant1:Wk 52, Participant2:Wk82, Participant3: Wk208,Participant4:Wk364,Participant5:Wk12,Participant6:Wk365,Participant7:Wk64,Participant8:Wk156,Participant9:Wk364,Participant10:Wk52,Participant11:Wk156,Participant12:Wk520
Head Circumference of Participants in Centimeters (cm)	Head Circumference of Participants was measured in Centimeters.	Participants1-12:Baseline, Participant1:Week(Wk)52, Participant2:Wk82, Participants3and4:Wk208, Participant5:Wk12, Participant6:Wk365, Participant7:Wk64, Participant8:Wk156, Participant9:Wk312, Participant10:Wk52, Participant11:Wk156, Participant12:Wk468
Motor Subscale of Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) Normative Composite Scores	Bayley-III: Instrument designed to measure developmental functioning of infants and toddlers between ages of 1 and 42 months (age adjustments for prematurity are accommodated with tool). Bayley-III administered up to 42 months of age and provides age specific norm-referenced composite scores for cognitive scales (91 items, composite score minimum 55 and maximum 145), language scale (98 items, composite score minimum 47 and maximum 153), motor scale (138 items, composite score minimum 46 and maximum 154) skills. For all raw scores (for scales), higher scores indicates greater number of developmental skills credited. For norm-based composite scales for motor scale, score of 100 defines average performance of given age group, scores of 85 and 115 are 1 standard deviation (SD) below an above mean, respectively, and scores of 70 and 130 are equivalent to 2 SD from mean.	Participants 1-12: Baseline, Participant-1: Week 52, Participant-2: Week 83, Participants 3 and 4: Week 104, Participant-6: Week 78, Participants 7 and 8: Week 26, Participant-9: Week 156, Participants 10 and 11: Week 26, Participant-12: Week 104
Gross Motor Function Measure (GMFM-88) Total Scores	GMFM-88 is developed specifically to detect quantitative changes in gross motor function that consists of 88 items organized into 5 dimensions: lying and rolling, sitting, crawling and kneeling, standing, and walking, running and jumping. Each item is scored on a 4-point Likert scale that ranges from 0 to 3, i.e., 0=cannot do; 1=initiated (less than [<] 10 percent [%] of task); 2=partially completed (10 to <100% of task); 3=task completion. The score for each dimension is expressed as percentage of the maximum score for that dimension. Total GMFM-88 score is obtained by adding percentage score for each dimension and dividing the sum by total number of dimensions. Total score ranges from 0 to 100, where higher score indicates better gross motor functions.	Participants 1-12: Baseline, Participants 1 and 2: Wk 52, Participants 3 and 4: Wk 208, Participant-6: Wk 359, Participant-7: Wk 26, Participant-8: Wk 156, Participant-9: Wk 312, Participant-11: Wk 156, Participant-12: Wk416
Pompe Pediatric Evaluation of Disability Inventory (Pompe PEDI) Scaled Scores	Pompe PEDI is disease specific version of PEDI developed to assess functional capabilities and performance in children with Pompe disease from 2 months up to adolescence. It consists of all items of original PEDI Functional Skills Scales and Caregiver Assistance Scales for three content domains: self-care, mobility, and social function. Additional items were added to Functional Skills Scales Mobility and Self-care domains. Norm-based scoring is developed for additional items and scoring algorithms for PEDI are adjusted to reflect normative data collected for Pompe PEDI. Scaled scores for each domain range from 0-100 and provide indication of performance of child along continuum of relatively easy to relatively difficult items in particular domain of PEDI, where higher score indicates increased degrees of functional performance.	Participants1-12:Baseline, Participants 1 and 2: Wk 52, Participants 3 and 4: Wk 208, Participant-6: Wk 359, Participant-7: Wk 52, Participant-8: Wk156, Participant-9: Wk 312, Participant-10: Wk 26, Participant-11: Wk 156, Participant-12: Wk 416
Cognitive and Language Subscales of Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) Normative Composite Scores	Bayley-III: Instrument designed to measure developmental functioning of infants and toddlers between ages of 1 and 42 months (age adjustments for prematurity are accommodated with tool). Bayley-III administered up to 42 months of age and provides age specific norm-referenced composite scores for cognitive scales (91 items, composite score minimum 55 and maximum 145), language scale (98 items, composite score minimum 47 and maximum 153), motor scale (138 items, composite score minimum 46 and maximum 154) skills. For all raw scores (for scales), higher scores indicates greater number of developmental skills credited. For norm-based composite scales for cognitive and language, score of 100 defines average performance of given age group, scores of 85 and 115 are 1 SD below an above mean, respectively, and scores of 70 and 130 are equivalent to 2 SD from mean.	Participants 1-12: Baseline, Participant-1: Week 52, Participant-2: Week 83, Participants 3 and 4: Week 104, Participant-6: Week 78, Participants 7 and 8: Week 26, Participant-9: Week 156, Participants 10 and 11:Week 26, Participant-12: Week 104
Brief Intelligence Quotient (IQ) Score of the Leiter International Performance Scale-Revised (Leiter-R)	Leiter Scale is designed as nonverbal measure of intellectual function, memory and attention for Participants with communication disorders, hearing impairments, motor impairments, certain types of learning disabilities. Leiter-R was administered to participants after aging out of Bayley-III (at 42 months of age) and before Leiter-3 utilization (per protocol, due to discontinuation of Leiter-R). Leiter-R scale consists of 2 groups of subtests: Visualization-Reasoning Battery, Attention-Memory Battery. Subtests in Leiter-R were Figure Ground, Form Completion, Sequential Order, Repeated Patterns using that 'Brief Scale IQ' was scored for estimation of intellectual ability. Brief-IQ scores range is 30-170, where higher scores indicates higher intelligence. Score of 100 is expected mean standard score at each age interval. 95% children in each age group (based on normative sample) are expected to score within 2 SD of mean.	Participants 1 and 2: Week 156, Participant-3: Week 260, Participant-4: Week 156, Participant-5: Week 208
Nonverbal Intelligence Quotient (IQ) Score of Leiter International Performance Scale - 3rd Edition (Leiter-3)	Leiter Scale: Designed as nonverbal measure of intellectual function, memory and attention for participants with communication disorders, hearing impairments, motor impairments, certain types of learning disabilities. Leiter-3 has 2 groups of subtests: cognitive battery and attention/memory battery. Nonverbal intelligence estimates global intellectual ability. The 4 cognitive battery subtests are: Figure Ground, Form Completion, Sequential Order, Classification-analogies along with 1 optional subset, Visual Patterns. Nonverbal IQ scores range is 30-170, which encompass 'severe delay' to 'extremely high/gifted', higher numbers indicates higher intelligence. Score of 100 is expected mean standard score at each age interval. 95% children in each age group (based on normative sample) are expected to score within 2 SD of mean.	Participant-1: Week 156, Participant-2: Week 312, Participant-3: Week 416

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	Adverse event (AE): any undesirable physical, psychological or behavioral effect experienced by participants during their participation in an investigational study, in conjunction with the use of the drug or biologic, whether or not product-related. Any untoward signs or symptoms experienced by the participant from the time of signing of the informed consent until completion of the study. Serious AE (SAE): any AE that resulted in any of the following outcomes: death, life-threatening experience, required hospitalization or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly, and important medical events. TEAEs: AEs that developed, worsened, or became serious during the treatment-emergent period (defined as the period from the first study drug administration until last study assessment).	From Baseline up to 13.25 years

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 26, 2008
• Primary Completion (ACTUAL): November 23, 2021
• Study Completion (ACTUAL): November 23, 2021

Study Registration Dates

• First Submitted: June 13, 2007
• First Submitted That Met QC Criteria: June 13, 2007
• First Posted (ESTIMATE): June 15, 2007

Study Record Updates

• Last Update Posted (ACTUAL): August 26, 2022
• Last Update Submitted That Met QC Criteria: July 29, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Glycogenesis 2
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Malnutrition; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Deficiency Diseases; Glycogen Storage Disease Type II; Glycogen Storage Disease
• Other Study ID Numbers: AGLU03606; LTS12869 (OTHER: Sanofi); U1111-1163-0368 (OTHER: UTN); 2021-005552-11 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No