Clinical trial NCT04910776: Clinical Study for Treatment-naïve IOPD Babies to Evaluate Efficacy and Safety of ERT With Avalglucosidase Alfa
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Glycogen Storage Disease Type II
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-06-02
Enrollment: 17
Sex: ALL
Minimum age (years): 0
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: Study duration may be variable by country, including at least completion of the PAP and ETP, and up to 4.08 years.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of participants who are alive and free of invasive ventilation at Week 52
timeFrame: Week 52
Secondary outcomes:
measure: Proportion of participants who are alive and free of invasive ventilation at 12 and 18 months of age
timeFrame: at 12 and 18 months of age
measure: Proportion of participants who are alive at Week 52
timeFrame: Week 52
measure: Proportion of participants who are alive at 12 and 18 months of age
timeFrame: at 12 and 18 months of age
measure: Proportion of participants who are free of ventilator use (invasive and non-invasive separate and combined) at Week 52
timeFrame: Week 52
measure: Proportion of participants who are free of supplemental oxygen use at Week 52
timeFrame: Week 52
measure: Change from baseline to Week 52 in left ventricular mass (LVM)-Z score
timeFrame: Week 52
measure: Change from baseline to Week 52 in Alberta Infant Motor Scale (AIMS) score
timeFrame: Week 52
measure: Change from baseline to Week 52 in body length Z-scores
timeFrame: Week 52
measure: Change from baseline to Week 52 in body weight Z-scores
timeFrame: Week 52
measure: Change from baseline to Week 52 in head circumference Z-scores
timeFrame: Week 52
measure: Change from baseline to Week 52 in body length percentiles
timeFrame: Week 52
measure: Change from baseline to Week 52 in body weight percentiles
timeFrame: Week 52
measure: Change from baseline to Week 52 in head circumference percentiles
timeFrame: Week 52
measure: Change from baseline to Week 52 in urinary Hex4
timeFrame: Week 52
measure: Number of participants experiencing at least 1 treatment-emergent adverse events (TEAE), including infusion associated reactions (IAR)
timeFrame: Week 52, Week 212
measure: Number of participants with abnormalities in physical examinations
timeFrame: Week 52, Week 208
measure: Number of participants with potentially clinically significant abnormality (PCSA) in clinical laboratory results
timeFrame: Week 52, Week 208
measure: Number of participants with PCSA in vital signs measurements
timeFrame: Week 52, Week 208
measure: Number of participants with PCSA in 12-lead electrocardiogram (ECG)
timeFrame: Week 52, Week 208
measure: Incidence of treatment-emergent anti-drug antibodies (ADA)
timeFrame: Week 52, Week 208
measure: Plasma concentration of avalglucosidase alfa
timeFrame: at Day 1, Week 12, and Week 52
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Hospital- Site Number : 8400006
state: California
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota- Site Number : 8400008
state: Minnesota
city: Hawthorne
country: United States
facility: Advanced Medical Genetics- Site Number : 8400002
state: New York
city: Durham
country: United States
facility: Duke University Medical Center- Site Number : 8400004
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center- Site Number : 8400001
state: Ohio
city: Seattle
country: United States
facility: Seattle Children's Hospital- Site Number : 8400003
state: Washington
city: Leuven
country: Belgium
facility: Investigational Site Number : 0560001
city: Qingdao
country: China
facility: Investigational Site Number : 1560002
city: Shanghai
country: China
facility: Investigational Site Number : 1560001
city: Bad Oeynhausen
country: Germany
facility: Investigational Site Number : 2760001
city: Monza
country: Italy
facility: Investigational Site Number : 3800002
state: Lombardia
city: Rotterdam
country: Netherlands
facility: Investigational Site Number : 5280001
city: Esplugues de Llobregat
country: Spain
facility: Investigational Site Number : 7240001
state: Catalunya [Cataluña]
city: Taipei City
country: Taiwan
facility: Investigational Site Number : 1580001
city: London
country: United Kingdom
facility: Investigational Site Number : 8260001
state: London, City Of
city: Manchester
country: United Kingdom
facility: Investigational Site Number : 8260002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: