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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

26 Aug 2022 → 27 Mar 2026

Decision date (initial)

2024-07-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Sanofi-Aventis Recherche & Developpement

External identifiers

EU CT number

2024-513859-33-00

EudraCT number

2020-004686-39

WHO UTN

U1111-1246-6645

ClinicalTrials.gov

NCT04910776

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Efficacy, Safety

To determine the effect of avalglucosidase alfa treatment on survival and invasive ventilator-free survival of IOPD participants ≤ 6 months of age after 52 weeks of treatment.

Secondary objectives 3

1. To determine the effect of avalglucosidase alfa treatment on survival and invasive ventilator-free survival at 12 and 18 months of age, as well the change in left ventricular mass Z-score (LVM Z-score); Alberta Infant Motor Scale (AIMS) score; body length, body weight, and head circumference Z scores; and urinary Hex4 at Week 52 in IOPD participants ≤ 6 months of age
2. To determine safety, tolerability, and immunogenicity of avalglucosidase alfa
3. To determine the pharmacokinetic (PK) profile at Week 12 and Week 52

Conditions and MedDRA coding

Glycogen storage disease type II

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000000-PIP00-00

Plan to share 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​

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 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).
2. Participants must have established cross-reactive immunological material (CRIM) status available prior to enrollment.
3. 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
4. Parents or legally authorized representative(s) must be capable of giving signed informed consent.

Exclusion criteria 6

1. Participants with symptoms of respiratory insufficiency, including any ventilation use (invasive or noninvasive) at the time of enrollment.
2. Participants with major congenital abnormality.
3. Participants with clinically significant organic disease (with the exception of symptoms relating to Pompe disease).
4. Participant received any Pompe disease specific treatment, eg ERT gene therapy.
5. Participant who has previously been treated in any clinical trial of avalglucosidase alfa.
6. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants who are alive and free of invasive ventilation at Week 52

Secondary endpoints 21

1. Proportion of participants who are alive and free of invasive ventilation at 12 and 18 months of age
2. Proportion of participants who are alive at Week 52
3. Proportion of participants who are alive at 12 and 18 months of age
4. Proportion of participants who are free of ventilator use (invasive and non-invasive separate and combined) at Week 52
5. Proportion of participants who are free of supplemental oxygen use at Week 52
6. Change from baseline to Week 52 in left ventricular mass (LVM)-Z score
7. Change from baseline to Week 52 in Alberta Infant Motor Scale (AIMS) score
8. Change from baseline to Week 52 in body length Z-scores
9. Change from baseline to Week 52 in body weight Z-scores
10. Change from baseline to Week 52 in head circumference Z-scores
11. Change from baseline to Week 52 in body length percentiles
12. Change from baseline to Week 52 in body weight percentiles
13. Change from baseline to Week 52 in head circumference percentiles
14. Change from baseline to Week 52 in urinary Hex4
15. Number of participants experiencing at least 1 treatment-emergent adverse events (TEAE), including infusion associated reactions (IAR)
16. Number of participants with abnormalities in physical examinations
17. Number of participants with potentially clinically significant abnormality (PCSA) in clinical laboratory results
18. Number of participants with PCSA in vital signs measurements
19. Number of participants with PCSA in 12-lead electrocardiogram (ECG)
20. Incidence of treatment-emergent anti-drug antibodies (ADA)
21. Plasma concentration of avalglucosidase alfa

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 9

Locations

5 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 42 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications