Clinical Study for Treatment-naïve IOPD Babies to Evaluate Efficacy and Safety of ERT With Avalglucosidase Alfa (Baby-COMET)

An Open-label, Multinational, Multicenter, Intravenous Infusion Study of the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Avalglucosidase Alfa in Treatment naïve Pediatric Participants With Infantile-Onset Pompe Disease (IOPD)

This is a single group, treatment, Phase 3, open-label study to assess efficacy, safety, pharmacokinetic (PK), pharmacodynamics (PD) of avalglucosidase alfa in treatment-naïve male and female participants with IOPD.

Study details include:

• Study duration: Screening - up to 4 weeks;
• Primary Analysis Period (PAP) - 52 weeks;
• Extended Treatment Period (ETP) - 52 weeks;
• Extended Long term Treatment Period (ELTP) - 104 weeks; 4-week follow-up period for a total study duration - up to 4.08 years.
• Treatment duration: Up to 4 years
• Visit frequency: every other week and potentially every week

Study Overview

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

Detailed Description

Study duration may be variable by country, but until avalglucosidase alfa is approved in the patient's country or up to 4.08 years, whichever comes first.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 3

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
• China
  • Qingdao, China, 266000
    • Recruiting
    • Investigational Site Number : 1560002
  • Shanghai, China, 200127
    • Recruiting
    • Investigational Site Number : 1560001
• Germany
  • Gießen, Germany, 35390
    • Recruiting
    • Investigational Site Number : 2760001
• Italy
  • Firenze, Italy, 50139
    • Recruiting
    • Investigational Site Number : 3800001
  • Lombardia
    • Monza, Lombardia, Italy, 20900
      • Recruiting
      • Investigational Site Number : 3800002
• Netherlands
  • Rotterdam, Netherlands, 3015 CN
    • 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
  • 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 1 year (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants must have confirmed diagnosis of infantile-onset Pompe disease defined as: the presence of 2 lysosomal acid α-glucosidase (GAA) pathogenic variants and a documented GAA deficiency from blood, skin, or muscle tissue; or the presence of 1 GAA pathogenic variant and a documented GAA deficiency from blood, skin and muscle tissue in 2 separate samples (from either 2 different tissues or from the same tissue but at 2 different sampling dates).
• Participants must have established cross-reactive immunological material (CRIM) status available prior to enrollment.

• Participants must have cardiomyopathy at the time of diagnosis: ie, left ventricular mass index (LVMI) equivalent to mean age specific LVMI

  • +1 standard deviation for participants diagnosed by newborn screening or sibling screening;
  • +2 standard deviation for participants diagnosed by clinical evaluation.
• Parents or legally authorized representative(s) must be capable of giving signed informed consent.

Exclusion Criteria:

• Participants with symptoms of respiratory insufficiency, including any ventilation use (invasive or noninvasive) at the time of enrollment.
• Participants with major congenital abnormality.
• Participants with clinically significant organic disease (with the exception of symptoms relating to Pompe disease).
• Participant received any Pompe disease specific treatment, eg enzyme-replacement gene therapy (ERT).
• Participant who has previously been treated in any clinical trial of avalglucosidase alfa.
• Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.

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

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Avalglucosidase alfa; Administered intravenously every 2 weeks	Drug: avalglucosidase alfa; Sterile lyophilized powder intravenous (IV) infusion; Other Names: GZ402666

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of participants who are alive and free of invasive ventilation at 12 and 18 months of age	at 12 and 18 months of age
Proportion of participants who are alive at Week 52	Week 52
Proportion of participants who are alive at 12 and 18 months of age	at 12 and 18 months of age
Proportion of participants who are free of ventilator use (invasive and non-invasive separate and combined) at Week 52	Week 52
Proportion of participants who are free of supplemental oxygen use at Week 52	Week 52
Change from baseline to Week 52 in left ventricular mass (LVM)-Z score	Week 52
Change from baseline to Week 52 in Alberta Infant Motor Scale (AIMS) score	Week 52
Change from baseline to Week 52 in body length Z-scores	Week 52
Change from baseline to Week 52 in body weight Z-scores	Week 52
Change from baseline to Week 52 in head circumference Z-scores	Week 52
Change from baseline to Week 52 in body length percentiles	Week 52
Change from baseline to Week 52 in body weight percentiles	Week 52
Change from baseline to Week 52 in head circumference percentiles	Week 52
Change from baseline to Week 52 in urinary Hex4	Week 52
Number of participants experiencing at least 1 treatment-emergent adverse events (TEAE), including infusion associated reactions (IAR)	Week 52, Week 212
Number of participants with abnormalities in physical examinations	Week 52, Week 208
Number of participants with potentially clinically significant abnormality (PCSA) in clinical laboratory results	Week 52, Week 208
Number of participants with PCSA in vital signs measurements	Week 52, Week 208
Number of participants with PCSA in 12-lead electrocardiogram (ECG)	Week 52, Week 208
Incidence of treatment-emergent anti-drug antibodies (ADA)	Week 52, Week 208
Plasma concentration of avalglucosidase alfa	at Day 1, Week 12, and Week 52

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2021
• Primary Completion (Estimated): December 27, 2024
• Study Completion (Estimated): August 28, 2026

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: June 1, 2021
• First Posted (Actual): June 2, 2021

Study Record Updates

• Last Update Posted (Actual): November 18, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 1, 2023

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: EFC14462; 2020-004686-39 (EudraCT Number); U1111-1246-6645 (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