Back to resultsA Study to Assess Safety and Efficacy of Avalglucosidase Alfa Administered Every Other Week in Pediatric Patients With Infantile-onset Pompe Disease Previously Treated With Alglucosidase Alfa (Mini-COMET)
Primary Purpose
Glycogen Storage Disease Type II-Pompe's Disease
Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Avalglucosidase alfa (GZ402666)
Alglucosidase alfa (GZ419829)
Sponsored by
About this trial
This is an interventional treatment trial for Glycogen Storage Disease Type II-Pompe's Disease
Eligibility Criteria
Inclusion criteria:
- The participants has confirmed acid alpha-glucosidase (GAA) enzyme deficiency from any tissue source.
- The participants who has reached legal age of majority as defined by local regulation, or the participant's legal guardian(s) must provide signed informed consent prior to performing any study-related procedures. If the participant is legally minor per local regulations, assent shall be obtained from participants, if applicable.
- The participants (and participant's legal guardian if participant is legally minor as defined by local regulation) must have the ability to comply with the clinical protocol.
- The participants is less than 18 years old.
- The participants, if female and of childbearing potential, must have a negative serum pregnancy test (beta-human chorionic gonadotropin) and must not breastfeeding at screening/Baseline.
- The participant has cardiomyopathy at the time of diagnosis: i.e., left ventricular mass index (LVMI) equivalent to mean age specific LVMI plus 2 standard deviations.
- The participant has been receiving a stable dose of alglucosidase alfa regularly for a minimum of 6 months immediately prior to study entry.
- For participants in Stage 1: The participant has documented evidence of clinical decline in at least 1 of the following parameters related to Pompe Disease and not related to intercurrent illness as assessed by the Investigator: respiratory function, motor skills, and/or cardiac parameters.
- For participants in Stage 2: The participant has documented evidence of suboptimal clinical response in at least 1 of the following parameters related to Pompe Disease and not related to intercurrent illness as assessed by the Investigator: respiratory function, motor skills, and/or new onset of ptosis.
Exclusion criteria:
- The participant has high antibody titer to alglucosidase alfa.
- The participant has a high risk for a severe allergic reaction to neoGAA (avalglucosidase alfa).
- The participant requires any prohibited concomitant medications (e.g., immune modulatory treatment) for the duration of the study.
- The participant has previously participated in any ACT14132 study cohort.
- Female participant of childbearing potential not protected by highly effective contraceptive method of birth control and/or who is unwilling or unable to tested for pregnancy.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Sites / Locations
- Investigational Site Number 8400002
- Investigational Site Number 8400001
- Investigational Site Number 8400005
- Investigational Site Number 2500003
- Investigational Site Number 2500001
- Investigational Site Number 3920001
- Investigational Site Number 3920002
- Investigational Site Number 1580001
- Investigational Site Number 8260001
- Investigational Site Number 8260002
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1: Avalglucosidase Alfa 20 mg/kg
Cohort 2: Avalglucosidase Alfa 40 mg/kg
Cohort 3a: Avalglucosidase Alfa 40 mg//kg
Cohort 3b: Alglucosidase Alfa in PAP
Arm Description
Avalglucosidase alfa, 20 mg/kg intravenous (IV) infusion every other week (qow) for 25 weeks in the Primary Analysis Period (PAP), followed by same treatment from Week 26 up to Week 371 in extension treatment period (ETP).
Avalglucosidase alfa 40 mg/kg IV infusion qow for 25 weeks in the PAP, followed by same treatment from Week 26 up to Week 371 in ETP.
After determination of the highest tolerated avalglucosidase alfa dose in Cohort 1 and Cohort 2 (after at least 5 participants in each Cohort 1 and Cohort 2 had received the 7th dose of avalglucosidase alfa or completed Week 13 with a minimum of 6 infusions), participants received avalglucosidase alfa 40 mg/kg (the highest tolerated dose) IV infusion qow for 25 weeks in PAP, followed by same treatment from Week 26 up to Week 371 in ETP.
After determination of the highest tolerated avalglucosidase alfa dose in Cohort 1 and Cohort 2 (after at least 5 participants in each Cohort 1 and Cohort 2 had received the 7th dose of avalglucosidase alfa or completed Week 13 with a minimum of 6 infusions), participants received alglucosidase alfa at their current stable dose (defined as dose [between 20 mg/kg qow and 40 mg/kg weekly as per physician] administered regularly for a minimum of 6 months immediately prior to entry in this study) IV infusion for 25 weeks in PAP. After PAP, participants received avalglucosidase alfa 40mg/kg IV infusion qow from Week 26 up to Week 371 in ETP.
Outcomes
Primary Outcome Measures
PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI)
Adverse event (AE): any untoward medical occurrence in participant received study drug & did not necessarily had to have causal relationship with treatment. TEAEs: AEs developed/worsened in grade/become serious during PAP period (from the time of 1st study drug dose up to Week 25). Serious AE(SAE): any untoward medical occurrence at any dose resulted in death, was life-threatening, required inpatient hospitalization, prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect or was medically important event. TEAEs included SAEs & non-SAEs. AESI:AE (serious/non-serious) of scientific & medical concern specific to Sponsor's product/program, for which ongoing monitoring & immediate notification by Investigator to Sponsor required.
PAP: Number of Participants With Infusion-associated Reactions (IARs)
IARs were defined as AESIs that occurred during either the infusion or the observation period following the infusion which were deemed to be related or possibly related to the study drug. Protocol-defined IARs: An AESIs that occurred during either the infusion or the observation period following the infusion which were deemed to be related or possibly related to study drug. Algorithm-defined IARs: any TEAE meeting either 1 or 2 criteria: 1) event occurred from the start of infusion to the end of infusion plus 24 hours, and considered related to study drug, 2) If an AE time component was missing, compared AE Start date with infusion start date and infusion end date. If an AE Start date was between infusion start date and infusion end date plus one day, and it was related to study drug.
Secondary Outcome Measures
PAP: Number of Participants With Anti-drug Antibody (ADA) Response
Anti-drug antibody response was categorized as: Treatment induced ADAs: ADAs developed de novo (seroconversion) following administration of study drug. Treatment boosted ADAs: pre-existing ADAs that were boosted at least two titer steps from Baseline (i.e., 4-fold increase in titers) followed by administration of study drug.
PAP: Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa
Cmax is the maximum observed plasma concentration.
PAP: Pharmacokinetic Parameter: Time to Achieve Maximum Observed Plasma Concentration (Tmax) of Avalglucosidase Alfa
Tmax is the time to achieve maximum plasma concentration.
PAP: Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-last) of Avalglucosidase Alfa
AUC0-last is the area under the plasma concentration versus time curve from time 0 to the time of last quantifiable concentration.
PAP: Pharmacokinetic Parameter: Terminal Half-life (t1/2) of Avalglucosidase Alfa
t1/2 is the time required for the plasma concentration of a drug to decrease by half of its initial concentration.
PAP: Pharmacokinetic Parameter: Clearance (CL) of Avalglucosidase Alfa
CL is defined as a quantitative measure of the rate at which a drug substance is removed from the body.
PAP: Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Avalglucosidase Alfa
Steady state volume of distribution (Vss) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
PAP: Change From Baseline in Gross Motor Function Measure-88 (GMFM-88) Test Scores at Week 25
GMFM-88 was developed specifically to detect quantitative changes in gross motor function. The GMFM-88 consisted of 88 items organized into 5 dimensions; lying and rolling (17 items); sitting (20 items); crawling and kneeling (14 items); standing (13 items) and walking, running and jumping (24 items). Each item was scored on a 4-point Likert scale with scores range: 0= cannot do; 1 = initiates less then [<] 10 percentage [%] of the task; 2 = partially completes [10% to <100% of the task] and 3 = task completion. The score for each dimension was expressed as a % of the maximum score for that dimension.Total percentage score was obtained by adding the percentage scores for each dimension and dividing the sum by the total number of dimensions. Total scores ranged from 0% to 100%; where higher scores indicated better motor functions.
PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25
GMFCS-E&R was a 5 level classification system for specific age ranges; observations were performed on 5 levels based on self-initiated movement, with emphasis on sitting, transfers, and mobility: Level I (walks without limitations), Level II (walks with limitations), Level III (walks using a hand-held mobility device), Level IV (self-mobility with limitations; may use powered mobility) and level V (transported in a manual wheel chair) (I to V). The distinctions between levels were based on functional limitations, the need for assistive mobility devices, and to a much lesser extent, quality of movement, and were designed to be meaningful in daily life. The lower level represented good motor functioning and higher level represented low motor functioning. Number of participants in each level of classification at Baseline and Week 25 were reported.
PAP: Change From Baseline in Pompe Pediatric Evaluation of Disability Inventory (Pompe-PEDI) Functional Skills Scale: Mobility Domain Test Score-Scaled Score at Week 25
Pompe-PEDI: disease specific version to assess functional capabilities and performance in children with Pompe disease from 2 months through adolescence. It comprised of Functional Skills Scale and Caregiver Assistance Scale; both scales had 3 domains: Self Care, Mobility, and Social Function. Mobility domain was used to measure change in mobility due to changes in muscle strength; consisted of 160 mobility items for participant/legal guardian. The total number of mobility items the child was capable of, was converted to a scaled score with a range of 0 to 100, where scores near "0" indicated low capability and scores near "100" indicated high capability), where higher score was indicative of greater functional ability. Scaled scores were used to interpret individual function and progress over time.
PAP: Change From Baseline in Quick Motor Function Test (QMFT) Scores at Week 25
QMFT was observer administered test comprised of 16 items specifically difficult for participants with Pompe disease. Each item was scored on 5-point ordinal scale ranged from 0 to 4 (higher score indicated better outcome). Total QMFT score was obtained by adding the scores of all items and ranged from 0 (unable to perform motor function tests) to 64 (normal muscle function), where higher score indicated better outcome/greater motor function.
PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25
Cardiac function was evaluated using LVM Z-score as assessed by echocardiogram in M-mode. Z-Scores indicated the number of standard deviations (SD) from the mean in a normal distribution. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in LVM Z-score. In this OM, absolute scores at Baseline and Week 25 along with Change from Baseline at Week 25 in LVM Z-score were reported.
PAP: Change From Baseline in Eyelid Position Measurements: Interpalpebral Fissure Distance (IPFD) - Left Non-Flash and Right Non-Flash at Week 25
IPFD is the widest vertical distance (in millimeters) between the upper eyelid and the lower eyelid when the participant is looking in "primary gaze" (i.e. normal gaze when looking straight forward). Images were taken while the participants was wearing a pair of empty eyeglass frames with millimeters rulers attached as a standardized tool to measure eyelid position without camera flash. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in measured distance.
PAP: Change From Baseline in Eyelid Position Measurements: Left and Right Margin Reflex Distance (MRD) at Week 25
The MRD is the vertical distance (in millimeters) between the light reflex and the upper eyelid when the participant was looking in "primary gaze" while fixating on a light source. Images were taken while the participants was wearing a pair of empty eyeglass frames with millimeters rulers attached as a standardized tool to measure eyelid position. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in measured distance.
PAP: Change From Baseline in Eyelid Position Measurements Assessed by Margin Pupil Distance (MPD) - Left Non-Flash and Right Non-Flash at Week 25
The MPD is the vertical distance (in millimeters) between the center of the pupil and the upper eyelid margin. Images were taken while the participants was wearing a pair of empty eyeglass frames with millimeters rulers attached as a standardized tool to measure eyelid position without camera flash. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in measured distance.
PAP: Change From Baseline in Creatine Kinase Value at Week 25
Change from Baseline in Creatine kinase value (to assess muscle damage) at Week 25 were reported in this OM.
ETP: Number of Participants With Treatment Emergent Adverse Events, Serious Treatment Emergent Adverse Events, and Adverse Event of Special Interest
Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2025).
ETP: Number of Participants With Infusion-associated Reactions
Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2025).
Full Information
NCT ID
NCT03019406
First Posted
December 20, 2016
Last Updated
June 26, 2023
Sponsor
Genzyme, a Sanofi Company
1. Study Identification
Unique Protocol Identification Number
NCT03019406
Brief Title
A Study to Assess Safety and Efficacy of Avalglucosidase Alfa Administered Every Other Week in Pediatric Patients With Infantile-onset Pompe Disease Previously Treated With Alglucosidase Alfa
Acronym
Mini-COMET
Official Title
An Open-label Ascending Dose Cohort Study to Assess the Safety, Pharmacokinetics, and Preliminary Efficacy of Avalglucosidase Alfa (NeoGAA, GZ402666) in Patients With Infantile-onset Pompe Disease Treated With Alglucosidase Alfa Who Demonstrate Clinical Decline or Sub-optimal Clinical Response
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 12, 2017 (Actual)
Primary Completion Date
September 30, 2019 (Actual)
Study Completion Date
June 15, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genzyme, a Sanofi Company
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Primary Objective:
To evaluate the safety profile of avalglucosidase alfa in participants with infantile-onset Pompe disease previously treated with alglucosidase alfa.
Secondary Objective:
To characterize the pharmacokinetic profile of avalglucosidase alfa and to evaluate the preliminary efficacy of avalglucosidase alfa in comparison to alglucosidase alfa.
Detailed Description
The duration of the study for each participant will be up to approximately 7 years, and consists of a 14-day screening period, that may be extended to up to 4 weeks in pre-specified situations. This is followed by a 25-week treatment period and an up to 346-week treatment extension period and a 4-week post-treatment observation period. Cohort 1 and 2 (Cohort 1: avalglucosidase alfa 20 milligrams per kilogram [mg/kg], Cohort 2: avalglucosidase alfa 40 mg/kg) will be non-randomized and Cohort 3 (Cohort 3a: avalglucosidase alfa 40 mg/kg [maximum tolerated dose] and Cohort 3b: alglucosidase alfa) will be randomized.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glycogen Storage Disease Type II-Pompe's Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1: Avalglucosidase Alfa 20 mg/kg
Arm Type
Experimental
Arm Description
Avalglucosidase alfa, 20 mg/kg intravenous (IV) infusion every other week (qow) for 25 weeks in the Primary Analysis Period (PAP), followed by same treatment from Week 26 up to Week 371 in extension treatment period (ETP).
Arm Title
Cohort 2: Avalglucosidase Alfa 40 mg/kg
Arm Type
Experimental
Arm Description
Avalglucosidase alfa 40 mg/kg IV infusion qow for 25 weeks in the PAP, followed by same treatment from Week 26 up to Week 371 in ETP.
Arm Title
Cohort 3a: Avalglucosidase Alfa 40 mg//kg
Arm Type
Experimental
Arm Description
After determination of the highest tolerated avalglucosidase alfa dose in Cohort 1 and Cohort 2 (after at least 5 participants in each Cohort 1 and Cohort 2 had received the 7th dose of avalglucosidase alfa or completed Week 13 with a minimum of 6 infusions), participants received avalglucosidase alfa 40 mg/kg (the highest tolerated dose) IV infusion qow for 25 weeks in PAP, followed by same treatment from Week 26 up to Week 371 in ETP.
Arm Title
Cohort 3b: Alglucosidase Alfa in PAP
Arm Type
Experimental
Arm Description
After determination of the highest tolerated avalglucosidase alfa dose in Cohort 1 and Cohort 2 (after at least 5 participants in each Cohort 1 and Cohort 2 had received the 7th dose of avalglucosidase alfa or completed Week 13 with a minimum of 6 infusions), participants received alglucosidase alfa at their current stable dose (defined as dose [between 20 mg/kg qow and 40 mg/kg weekly as per physician] administered regularly for a minimum of 6 months immediately prior to entry in this study) IV infusion for 25 weeks in PAP. After PAP, participants received avalglucosidase alfa 40mg/kg IV infusion qow from Week 26 up to Week 371 in ETP.
Intervention Type
Drug
Intervention Name(s)
Avalglucosidase alfa (GZ402666)
Other Intervention Name(s)
neoGAA
Intervention Description
Pharmaceutical form: powder for concentrate for solution for infusion,
Route of administration: IV
Intervention Type
Drug
Intervention Name(s)
Alglucosidase alfa (GZ419829)
Other Intervention Name(s)
Myozyme®, Lumizyme®
Intervention Description
Pharmaceutical form: powder for concentrate for solution for infusion,
Route of administration: IV
Primary Outcome Measure Information:
Title
PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI)
Description
Adverse event (AE): any untoward medical occurrence in participant received study drug & did not necessarily had to have causal relationship with treatment. TEAEs: AEs developed/worsened in grade/become serious during PAP period (from the time of 1st study drug dose up to Week 25). Serious AE(SAE): any untoward medical occurrence at any dose resulted in death, was life-threatening, required inpatient hospitalization, prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect or was medically important event. TEAEs included SAEs & non-SAEs. AESI:AE (serious/non-serious) of scientific & medical concern specific to Sponsor's product/program, for which ongoing monitoring & immediate notification by Investigator to Sponsor required.
Time Frame
From Baseline to Week 25
Title
PAP: Number of Participants With Infusion-associated Reactions (IARs)
Description
IARs were defined as AESIs that occurred during either the infusion or the observation period following the infusion which were deemed to be related or possibly related to the study drug. Protocol-defined IARs: An AESIs that occurred during either the infusion or the observation period following the infusion which were deemed to be related or possibly related to study drug. Algorithm-defined IARs: any TEAE meeting either 1 or 2 criteria: 1) event occurred from the start of infusion to the end of infusion plus 24 hours, and considered related to study drug, 2) If an AE time component was missing, compared AE Start date with infusion start date and infusion end date. If an AE Start date was between infusion start date and infusion end date plus one day, and it was related to study drug.
Time Frame
From Baseline to Week 25
Secondary Outcome Measure Information:
Title
PAP: Number of Participants With Anti-drug Antibody (ADA) Response
Description
Anti-drug antibody response was categorized as: Treatment induced ADAs: ADAs developed de novo (seroconversion) following administration of study drug. Treatment boosted ADAs: pre-existing ADAs that were boosted at least two titer steps from Baseline (i.e., 4-fold increase in titers) followed by administration of study drug.
Time Frame
From Baseline to Week 25
Title
PAP: Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa
Description
Cmax is the maximum observed plasma concentration.
Time Frame
Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 and 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25
Title
PAP: Pharmacokinetic Parameter: Time to Achieve Maximum Observed Plasma Concentration (Tmax) of Avalglucosidase Alfa
Description
Tmax is the time to achieve maximum plasma concentration.
Time Frame
Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 and 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25
Title
PAP: Pharmacokinetic Parameter: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-last) of Avalglucosidase Alfa
Description
AUC0-last is the area under the plasma concentration versus time curve from time 0 to the time of last quantifiable concentration.
Time Frame
Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 & 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25
Title
PAP: Pharmacokinetic Parameter: Terminal Half-life (t1/2) of Avalglucosidase Alfa
Description
t1/2 is the time required for the plasma concentration of a drug to decrease by half of its initial concentration.
Time Frame
Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 & 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25
Title
PAP: Pharmacokinetic Parameter: Clearance (CL) of Avalglucosidase Alfa
Description
CL is defined as a quantitative measure of the rate at which a drug substance is removed from the body.
Time Frame
Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 and 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25
Title
PAP: Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Avalglucosidase Alfa
Description
Steady state volume of distribution (Vss) is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time Frame
Cohort 1: pre-dose; at end of infusion; and at 2, 4, 6, and 8 hours after end of infusion on Day 1 (Week 1) and Week 25 Cohort 2 & 3: pre-dose; at end of infusion; and at 2, 4, 6, 8, and 12 to 16 hours after end of infusion on Day 1 (Week 1) and Week 25
Title
PAP: Change From Baseline in Gross Motor Function Measure-88 (GMFM-88) Test Scores at Week 25
Description
GMFM-88 was developed specifically to detect quantitative changes in gross motor function. The GMFM-88 consisted of 88 items organized into 5 dimensions; lying and rolling (17 items); sitting (20 items); crawling and kneeling (14 items); standing (13 items) and walking, running and jumping (24 items). Each item was scored on a 4-point Likert scale with scores range: 0= cannot do; 1 = initiates less then [<] 10 percentage [%] of the task; 2 = partially completes [10% to <100% of the task] and 3 = task completion. The score for each dimension was expressed as a % of the maximum score for that dimension.Total percentage score was obtained by adding the percentage scores for each dimension and dividing the sum by the total number of dimensions. Total scores ranged from 0% to 100%; where higher scores indicated better motor functions.
Time Frame
Baseline, Week 25
Title
PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25
Description
GMFCS-E&R was a 5 level classification system for specific age ranges; observations were performed on 5 levels based on self-initiated movement, with emphasis on sitting, transfers, and mobility: Level I (walks without limitations), Level II (walks with limitations), Level III (walks using a hand-held mobility device), Level IV (self-mobility with limitations; may use powered mobility) and level V (transported in a manual wheel chair) (I to V). The distinctions between levels were based on functional limitations, the need for assistive mobility devices, and to a much lesser extent, quality of movement, and were designed to be meaningful in daily life. The lower level represented good motor functioning and higher level represented low motor functioning. Number of participants in each level of classification at Baseline and Week 25 were reported.
Time Frame
Baseline, Week 25
Title
PAP: Change From Baseline in Pompe Pediatric Evaluation of Disability Inventory (Pompe-PEDI) Functional Skills Scale: Mobility Domain Test Score-Scaled Score at Week 25
Description
Pompe-PEDI: disease specific version to assess functional capabilities and performance in children with Pompe disease from 2 months through adolescence. It comprised of Functional Skills Scale and Caregiver Assistance Scale; both scales had 3 domains: Self Care, Mobility, and Social Function. Mobility domain was used to measure change in mobility due to changes in muscle strength; consisted of 160 mobility items for participant/legal guardian. The total number of mobility items the child was capable of, was converted to a scaled score with a range of 0 to 100, where scores near "0" indicated low capability and scores near "100" indicated high capability), where higher score was indicative of greater functional ability. Scaled scores were used to interpret individual function and progress over time.
Time Frame
Baseline, Week 25
Title
PAP: Change From Baseline in Quick Motor Function Test (QMFT) Scores at Week 25
Description
QMFT was observer administered test comprised of 16 items specifically difficult for participants with Pompe disease. Each item was scored on 5-point ordinal scale ranged from 0 to 4 (higher score indicated better outcome). Total QMFT score was obtained by adding the scores of all items and ranged from 0 (unable to perform motor function tests) to 64 (normal muscle function), where higher score indicated better outcome/greater motor function.
Time Frame
Baseline, Week 25
Title
PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25
Description
Cardiac function was evaluated using LVM Z-score as assessed by echocardiogram in M-mode. Z-Scores indicated the number of standard deviations (SD) from the mean in a normal distribution. The normal range is -2 to 2 and greater than 2 may indicate left ventricular hypertrophy. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in LVM Z-score. In this OM, absolute scores at Baseline and Week 25 along with Change from Baseline at Week 25 in LVM Z-score were reported.
Time Frame
Baseline, Week 25
Title
PAP: Change From Baseline in Eyelid Position Measurements: Interpalpebral Fissure Distance (IPFD) - Left Non-Flash and Right Non-Flash at Week 25
Description
IPFD is the widest vertical distance (in millimeters) between the upper eyelid and the lower eyelid when the participant is looking in "primary gaze" (i.e. normal gaze when looking straight forward). Images were taken while the participants was wearing a pair of empty eyeglass frames with millimeters rulers attached as a standardized tool to measure eyelid position without camera flash. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in measured distance.
Time Frame
Baseline, Week 25
Title
PAP: Change From Baseline in Eyelid Position Measurements: Left and Right Margin Reflex Distance (MRD) at Week 25
Description
The MRD is the vertical distance (in millimeters) between the light reflex and the upper eyelid when the participant was looking in "primary gaze" while fixating on a light source. Images were taken while the participants was wearing a pair of empty eyeglass frames with millimeters rulers attached as a standardized tool to measure eyelid position. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in measured distance.
Time Frame
Baseline, Week 25
Title
PAP: Change From Baseline in Eyelid Position Measurements Assessed by Margin Pupil Distance (MPD) - Left Non-Flash and Right Non-Flash at Week 25
Description
The MPD is the vertical distance (in millimeters) between the center of the pupil and the upper eyelid margin. Images were taken while the participants was wearing a pair of empty eyeglass frames with millimeters rulers attached as a standardized tool to measure eyelid position without camera flash. A negative change from Baseline indicated a decrease and positive change from Baseline indicated an increase in measured distance.
Time Frame
Baseline, Week 25
Title
PAP: Change From Baseline in Creatine Kinase Value at Week 25
Description
Change from Baseline in Creatine kinase value (to assess muscle damage) at Week 25 were reported in this OM.
Time Frame
Baseline, Week 25
Title
ETP: Number of Participants With Treatment Emergent Adverse Events, Serious Treatment Emergent Adverse Events, and Adverse Event of Special Interest
Description
Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2025).
Time Frame
From Week 26 to Week 371
Title
ETP: Number of Participants With Infusion-associated Reactions
Description
Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (December 2025).
Time Frame
From Week 26 to Week 371
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
The participants has confirmed acid alpha-glucosidase (GAA) enzyme deficiency from any tissue source.
The participants who has reached legal age of majority as defined by local regulation, or the participant's legal guardian(s) must provide signed informed consent prior to performing any study-related procedures. If the participant is legally minor per local regulations, assent shall be obtained from participants, if applicable.
The participants (and participant's legal guardian if participant is legally minor as defined by local regulation) must have the ability to comply with the clinical protocol.
The participants is less than 18 years old.
The participants, if female and of childbearing potential, must have a negative serum pregnancy test (beta-human chorionic gonadotropin) and must not breastfeeding at screening/Baseline.
The participant has cardiomyopathy at the time of diagnosis: i.e., left ventricular mass index (LVMI) equivalent to mean age specific LVMI plus 2 standard deviations.
The participant has been receiving a stable dose of alglucosidase alfa regularly for a minimum of 6 months immediately prior to study entry.
For participants in Stage 1: The participant has documented evidence of clinical decline in at least 1 of the following parameters related to Pompe Disease and not related to intercurrent illness as assessed by the Investigator: respiratory function, motor skills, and/or cardiac parameters.
For participants in Stage 2: The participant has documented evidence of suboptimal clinical response in at least 1 of the following parameters related to Pompe Disease and not related to intercurrent illness as assessed by the Investigator: respiratory function, motor skills, and/or new onset of ptosis.
Exclusion criteria:
The participant has high antibody titer to alglucosidase alfa.
The participant has a high risk for a severe allergic reaction to neoGAA (avalglucosidase alfa).
The participant requires any prohibited concomitant medications (e.g., immune modulatory treatment) for the duration of the study.
The participant has previously participated in any ACT14132 study cohort.
Female participant of childbearing potential not protected by highly effective contraceptive method of birth control and/or who is unwilling or unable to tested for pregnancy.
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 8400002
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Facility Name
Investigational Site Number 8400001
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Investigational Site Number 8400005
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Investigational Site Number 2500003
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
Investigational Site Number 2500001
City
Tours Cedex 1
ZIP/Postal Code
37044
Country
France
Facility Name
Investigational Site Number 3920001
City
Fuchu-Shi
Country
Japan
Facility Name
Investigational Site Number 3920002
City
Fuchu-Shi
Country
Japan
Facility Name
Investigational Site Number 1580001
City
Taipei
ZIP/Postal Code
10043
Country
Taiwan
Facility Name
Investigational Site Number 8260001
City
London
ZIP/Postal Code
WC1N 3JH
Country
United Kingdom
Facility Name
Investigational Site Number 8260002
City
Manchester
ZIP/Postal Code
M13 9WL
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
Learn more about this trial
A Study to Assess Safety and Efficacy of Avalglucosidase Alfa Administered Every Other Week in Pediatric Patients With Infantile-onset Pompe Disease Previously Treated With Alglucosidase Alfa
We'll reach out to this number within 24 hrs