Clinical trial NCT04848779: A Prospective Study to Observe & Describe Clinical Outcomes of Alglucosidase Alfa Treatment in Patients ≤6 Months of Age With Infantile-onset Pompe Disease (IOPD)
Official title: A Prospective Observational Study to Describe Clinical Outcomes of Alglucosidase Alfa Treatment in Patients ≤6 Months of Age With Infantile-onset Pompe Disease (IOPD)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Glycogen Storage Disease Type II
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2021-04-19
Enrollment: 16
Sex: ALL
Minimum age (years): 0
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of participants alive and free of invasive ventilation at Week 52 of treatment
timeFrame: Week 52
Secondary outcomes:
measure: Proportion of participants 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 alive at Week 52 of treatment
timeFrame: Week 52
measure: Proportion of participants alive at 12 months and 18 months of age
timeFrame: at 12 and 18 months of age
measure: Proportion of participants free of ventilator use and free of supplemental oxygen use at Week 52
timeFrame: Week 52
measure: Change from baseline to Week 52 in LVM Z score
timeFrame: from baseline to Week 52
measure: Change from baseline to Week 52 in AIMS score
timeFrame: from baseline to Week 52
measure: Change from baseline to Week 52 in body length Z-scores
timeFrame: from baseline to Week 52
measure: Change from baseline to Week 52 in body weight Z-scores
timeFrame: from baseline to Week 52
measure: Change from baseline to Week 52 in head circumference Z-scores
timeFrame: from baseline to Week 52
measure: Change from baseline to Week 52 in body length percentiles
timeFrame: from baseline to Week 52
measure: Change from baseline to Week 52 in body weight percentiles
timeFrame: from baseline to Week 52
measure: Change from baseline to Week 52 in head circumference percentiles
timeFrame: from baseline to Week 52
measure: Change from baseline to Week 52 in urinary Hex4
timeFrame: from baseline to Week 52
measure: Number of participants experiencing at least 1 treatment-emergent adverse events (TEAE), including infusion-associated reactions (IAR)
timeFrame: From inclusion for 104 weeks
measure: Number of participants with abnormalities in physical examinations
timeFrame: From inclusion for 104 weeks
measure: Number of participants with abnormalities in clinical laboratory results
timeFrame: From inclusion for 104 weeks
measure: Number of participants with abnormalities in vital signs measurements
timeFrame: From inclusion for 104 weeks
measure: Number of participants with abnormalities in 12-lead electrocardiogram (ECG)
timeFrame: From inclusion for 104 weeks
measure: Incidence of treatment-emergent antidrug antibodies (ADA)
timeFrame: From inclusion for 104 weeks
Other outcomes:
Locations:
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: Memphis
country: United States
facility: Le Bonheur Children's Hospital- Site Number : 8400005
state: Tennessee
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: Tours
country: France
facility: Investigational Site Number : 2500001
city: Gießen
country: Germany
facility: Investigational Site Number : 2760001
city: Monza
country: Italy
facility: Investigational Site Number : 3800002
state: Monza E Brianza
city: Firenze
country: Italy
facility: Investigational Site Number : 3800001
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: