A Prospective Study to Observe & Describe Clinical Outcomes of Alglucosidase Alfa Treatment in Patients ≤6 Months of Age With Infantile-onset Pompe Disease (IOPD)

A Prospective Observational Study to Describe Clinical Outcomes of Alglucosidase Alfa Treatment in Patients ≤6 Months of Age With Infantile-onset Pompe Disease (IOPD)

Primary Objective:

To describe the effect of routine practice with alglucosidase alfa in patients with IOPD ≤6 months of age, on invasive ventilation-free survival after 52 weeks of treatment.

Secondary Objectives:

• To describe the effect of routine practice with alglucosidase alfa on invasive ventilation-free survival and survival at 12 and 18 months of age, as well as on change in left ventricular mass (LVM) Z score, Alberta Infant Motor Scale (AIMS) score, body weight, body length, and head circumference Z scores, and urinary glucose tetrasaccharide (Hex4), at Week 52 of treatment.
• To describe the safety, tolerability, and immunogenicity of alglucosidase alfa in the routine practice of IOPD treatment.

Study Overview

• Status: Recruiting
• Conditions: Glycogen Storage Disease Type II
• Intervention / Treatment: Drug: Alglucosidase alfa GZ419829

Detailed Description

The planned duration of observation for each participant will be 104 weeks after enrollment, to determine secondary outcomes at 18 months (approximately 78 weeks) of age.

• Study Type: Observational
• Enrollment (Estimated): 16

Contacts and Locations

• Study Contact: Name: Trial Transparency email recommended (Toll free number for US & Canada); Phone Number: option 6 800-633-1610; Email: contact-us@sanofi.com

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • Investigational Site Number : 0560001
• France
  • Tours, France, 37044
    • Recruiting
    • Investigational Site Number : 2500001
• Germany
  • Gießen, Germany, 35392
    • Recruiting
    • Investigational Site Number : 2760001
• Italy
  • Firenze, Italy, 50139
    • Recruiting
    • Investigational Site Number : 3800001
  • Monza E Brianza
    • Monza, Monza E Brianza, Italy, 20052
      • Recruiting
      • Investigational Site Number : 3800002
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Recruiting
    • Investigational Site Number : 5280001
• Spain
  • Catalunya [Cataluña]
    • Esplugues de Llobregat, Catalunya [Cataluña], Spain, 08950
      • Recruiting
      • Investigational Site Number : 7240001
• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • Investigational Site Number : 1580001
• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Recruiting
    • Investigational Site Number : 8260002
  • London, City Of
    • London, London, City Of, United Kingdom, WC1N 3JH
      • Recruiting
      • Investigational Site Number : 8260001
• United States
  • New York
    • Valhalla, New York, United States, 10595
      • Recruiting
      • Boston Children's Health Physicians Site Number : 8400002
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center Site Number : 8400004
  • Ohio
    • Cincinnati, Ohio, United States, 45229-3039
      • Recruiting
      • Cincinnati Children's Hospital Medical Center - PIN Site Number : 8400001
  • Washington
    • Seattle, Washington, United States, 98040
      • Recruiting
      • Seattle Childrens Hospital and Regional Medical Center Site Number : 8400003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 6 months (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Confirmly diagnosed IOPD patients 6 months or less of age (corrected for gestational age if needed), treated or planned to be treated with alglucosidase alfa, at the time of study inclusion.

Description

Inclusion Criteria:

• At the time of informed consent, participants must be ≤6 months of age, corrected for gestation if necessary. Gestational age <40 weeks will be adjusted to a full-term gestational age of 40 weeks.
• Participants must have alglucosidase alfa enzyme replacement therapy (ERT) planned or initiated for IOPD treatment irrespective of study participation, according to the treating physician's decision regarding participants' routine disease management.
• Participants must have available and accessible medical records from the time of IOPD diagnosis and from subsequent follow-up.
• Participants must have a confirmed diagnosis of IOPD, defined as presence of 2 pathogenic acid alpha glucosidase (GAA) variants and documented GAA deficiency in blood (dried blood spot [DBS] accepted), skin, or muscle tissue, or presence of 1 pathogenic GAA variant and documented GAA deficiency in blood, skin, or muscle tissue from separate samples (either from 2 different tissues or from the same tissue but at 2 different sampling dates.) (DBS and leukocytes are acceptable as 2 different samples from blood).
• Participants must have established cross-reacting immunologic material (CRIM) status available prior to enrollment. CRIM status may be provided by historical CRIM testing results or prediction of CRIM status based on genotyping performed at a Clinical Laboratory Improvement Amendments (CLIA) or other appropriately certified genetic laboratory.

• Participants must have cardiomyopathy at the time of diagnosis (LVMI equivalent to mean age-specific LVMI):

  • LVMI +1 standard deviation (SD) in participants diagnosed by newborn or sibling screening,
  • LVMI +2 SD in participants diagnosed by clinical evaluation.
• Participants must have informed consent provided by parent(s)/legally acceptable representatives (LARs).

Exclusion Criteria:

• Participants with respiratory insufficiency, defined as:

  • Oxygen saturation <90% on room air as determined by pulse oximetry,
  • Venous partial pressure of carbon dioxide (pCO2) >55 mmHg or arterial pCO2 >40 mmHg on room air,
  • Use of invasive (with intubation or tracheostomy) or noninvasive (no intubation or tracheostomy) ventilation at enrollment, for participants not having started ERT at enrollment,
  • Use of invasive or noninvasive ventilation at the time of ERT initiation, for participants having started ERT before enrollment.
• Participants with major congenital abnormality including heart defect, neural tube defect, or Down syndrome that, in the opinion of the investigator, would preclude participation in the study or potentially decrease survival.
• Participants with clinically significant organic disease other than signs/symptoms related to Pompe disease, including clinically significant cardiovascular, hepatic, pulmonary, neurologic, or renal disease, or other medical condition, serious intercurrent illness, or circumstance that, in the opinion of the investigator, would preclude participation or potentially decrease survival.
• Previous or ongoing treatment in any clinical trial of, or managed access program for, avalglucosidase alfa or any other Pompe disease-specific therapy.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1	Drug: Alglucosidase alfa GZ419829; Pharmaceutical form: Lyophilized powder for solution Route of administration: intravenous; Other Names: Myozyme

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of participants alive and free of invasive ventilation at Week 52 of treatment	Week 52

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of participants alive and free of invasive ventilation at 12 and 18 months of age	at 12 and 18 months of age
Proportion of participants alive at Week 52 of treatment	Week 52
Proportion of participants alive at 12 months and 18 months of age	at 12 and 18 months of age
Proportion of participants free of ventilator use and free of supplemental oxygen use at Week 52	Week 52
Change from baseline to Week 52 in LVM Z score	from baseline to Week 52
Change from baseline to Week 52 in AIMS score	from baseline to Week 52
Change from baseline to Week 52 in body length Z-scores	from baseline to Week 52
Change from baseline to Week 52 in body weight Z-scores	from baseline to Week 52
Change from baseline to Week 52 in head circumference Z-scores	from baseline to Week 52
Change from baseline to Week 52 in body length percentiles	from baseline to Week 52
Change from baseline to Week 52 in body weight percentiles	from baseline to Week 52
Change from baseline to Week 52 in head circumference percentiles	from baseline to Week 52
Change from baseline to Week 52 in urinary Hex4	from baseline to Week 52
Number of participants experiencing at least 1 treatment-emergent adverse events (TEAE), including infusion-associated reactions (IAR)	From inclusion for 104 weeks
Number of participants with abnormalities in physical examinations	From inclusion for 104 weeks
Number of participants with abnormalities in clinical laboratory results	From inclusion for 104 weeks
Number of participants with abnormalities in vital signs measurements	From inclusion for 104 weeks
Number of participants with abnormalities in 12-lead electrocardiogram (ECG)	From inclusion for 104 weeks
Incidence of treatment-emergent antidrug antibodies (ADA)	From inclusion for 104 weeks

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: Clinical Sciences & Operations, Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2021
• Primary Completion (Estimated): March 30, 2026
• Study Completion (Estimated): March 30, 2026

Study Registration Dates

• First Submitted: March 29, 2021
• First Submitted That Met QC Criteria: April 13, 2021
• First Posted (Actual): April 19, 2021

Study Record Updates

• Last Update Posted (Estimated): February 9, 2024
• Last Update Submitted That Met QC Criteria: February 8, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease Type II; Glycogen Storage Disease
• Other Study ID Numbers: OBS17003; U1111-1266-4848 (Registry Identifier: ICTRP)

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
• product manufactured in and exported from the U.S.: No