Clinical Trial Results:
A Single Arm, Prospective, Open-label, Multi-center Study to Evaluate Efficacy and Safety in Chinese Patients with Infantile-Onset Pompe Disease with One Year Alglucosidase Alfa Treatment
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Summary
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EudraCT number |
2021-004047-25 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
30 Dec 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Sep 2021
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First version publication date |
11 Sep 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ALGMYL08718
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03687333 | ||
WHO universal trial number (UTN) |
U1111-1203-8484 | ||
Other trial identifiers |
Study Name: APOLLO-IOPD | ||
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Sponsors
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Sponsor organisation name |
Genzyme, a Sanofi Company
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Sponsor organisation address |
50 Binney Street, Cambridge, Massachusetts, United States, 02142
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Public contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
22 Mar 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Dec 2020
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to evaluate effect of 52-week treatment with Alglucosidase Alfa in the extension of survival and improvement of cardiomyopathy measured by Left Ventricular Mass Index (LVMI) in Chinese subjects with infantile-onset Pompe Disease (IOPD).
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Protection of trial subjects |
The study was conducted by investigators experienced in the treatment of paediatric patients. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimised. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia might have been used to minimise distress and discomfort.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Dec 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
China: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
10
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Study was conducted at 4 active study centres in China. A total of 12 subjects were screened between 04 Dec 2018 and 3 Dec 2019, of which 02 subjects failed screening mainly due to unmet inclusion criteria and/or met exclusion criteria and withdrawal of the informed consent by parents or legal guardians of subject, respectively. | ||||||||||
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Pre-assignment
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Screening details |
A total of 10 subjects were treated in this study. | ||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Alglucosidase Alfa | ||||||||||
Arm description |
Subjects received Alglucosidase alfa, 20 milligrams per kilogram (mg/kg) body weight intravenous (IV) infusion every 2 weeks for up to 52 weeks. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Alglucosidase alfa
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Investigational medicinal product code |
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Other name |
Myozyme®
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Pharmaceutical forms |
Powder for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Alglucosidase alfa 20 mg/kg body weight IV infusion every 2 weeks for 52 Weeks. Dose was allowed to be increased up to 40 mg/kg for subjects who showed sub-optimal response to the treatment.
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Baseline characteristics reporting groups
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Reporting group title |
Alglucosidase Alfa
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Reporting group description |
Subjects received Alglucosidase alfa, 20 milligrams per kilogram (mg/kg) body weight intravenous (IV) infusion every 2 weeks for up to 52 weeks. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Alglucosidase Alfa
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Reporting group description |
Subjects received Alglucosidase alfa, 20 milligrams per kilogram (mg/kg) body weight intravenous (IV) infusion every 2 weeks for up to 52 weeks. | ||
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End point title |
Percentage of Subjects Who Survived at Week 52 [1] | ||||||||
End point description |
Binomial proportion and its 95% confidence interval were used to analyse the percentage of survivals. Analysis was performed on intent-to-treat (ITT) population which included all subjects treated with Alglucosidase alfa.
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End point type |
Primary
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End point timeframe |
At Week 52
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As the endpoint was descriptive in nature, no inferential statistical analysis was provided. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Left Ventricular Mass (LVM) Index at Week 52 [2] | ||||||||
End point description |
LVM were assessed by echocardiograms. LVM index was an index value derived by normalizing LVM by body surface area. LVM index provides evidence of cardiomyopathy. LVM index values less than (<) 65 gram per metre quare (g/m^2) were considered as normal and LVM index values greater than or equal to (>=) 65 g/m^2 were considered as abnormal. Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who were evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline, Week 52
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As the endpoint was descriptive in nature, no inferential statistical analysis was provided. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Invasive Ventilator Use-Free Survival at Week 52 | ||||||||
End point description |
Invasive ventilator-free survival was defined as the time during which the subject was alive and not invasively ventilated. Binomial proportion and its 95% confidence interval were used to analyse the percentage of invasive ventilator use-free survival. Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who did not use any invasive ventilator and were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
At Week 52
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Any Ventilator Use-Free Survival at Week 52 | ||||||||
End point description |
Ventilator-free survival was defined as the time during which the subject was alive and not ventilated. Binomial proportion and its 95% confidence interval were used to analyse the percentage of any ventilator use-free survival. Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who did not use any ventilator and were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
At Week 52
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Physical Growth at Week 52: Length | ||||||||
End point description |
Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 52
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Physical Growth at Week 52: Weight | ||||||||
End point description |
Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 52
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Motor Development Milestones Achieved at Week 52 | ||||||||
End point description |
Motor development was assessed by a 11-point scale ranged from 0 (worst motor behavior) to 11 (better motor behavior). A higher score means better motor behavior. Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
At Week 52
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Motor Development Status at Week 52 | ||||||||
End point description |
Motor development was assessed by a 11-point scale ranged from 0 (worst motor behavior) to 11 (better motor behavior). A higher score means better motor status. Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 52
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in GESELL Developmental Scale at Week 52 | ||||||||||||||||
End point description |
GESELL developmental scale was used to assess motor development and functional independence of infants. The GESELL developmental scale measures: adaptive (cognitive) behavior, motor, language behavior, and personal-social behavior. Higher measured mature age represented higher developmental quotient, and higher developmental quotient represented better status. Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 52
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Percentage of Subjects With Signs and/or Symptoms of Cardiac Failure at Week 52 | ||||||||
End point description |
Analysis was performed on ITT population. Here, ‘number of subjects analysed’ signifies those subjects who were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
At Week 52
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse events (AEs) were collected from first dose of investigational medicinal product (IMP) up to 30 days after the last dose of IMP (Week 56).
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Adverse event reporting additional description |
Reported AEs were treatment-emergent AEs (TEAEs), that developed/worsened or became serious during during TEAE period (from first dose of IMP up to 30 days after last dose of IMP [Week 56]). Analysis was performed on safety population which included subjects who received at least 1 dose or part of a dose of IMP.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.1
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Reporting groups
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Reporting group title |
Alglucosidase Alfa
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Reporting group description |
Subjects received Alglucosidase alfa, 20 mg/kg body weight IV infusion every 2 weeks for up to 52 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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08 Oct 2018 |
Following changes were made: Adjustment of instruction of use of MYOZYME® for those subjects whose cross-reacting immunologic material (CRIM) was negative, revised to “CRIM status was rapidly inferred by gene mutation analysis, using an established mutation database.” Adjustment of assessment during treatment, revised to “blood sample was collected for CRIM status determination through genotyping at screening visit in each site, only if written results was not available.”
On May 2021, following changes were made: Due to adenosine deaminase (ADA) test was not done in China, according to global medical suggestions to of removing the ADA related content. The Kaplan-Meier methodology and modified relevant description was removed due to not enough sample size for Kaplan-Meier methodology.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
