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
| Registry | NCT03019406, acronym Mini-COMET |
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| Status | Active not recruiting |
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| Phase | Phase 2 |
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| Study type | Interventional; randomized, parallel, masking: none, treatment |
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| Enrollment | 22 (Actual) |
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| Sponsor | Genzyme, a Sanofi Company (Industry) |
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| Conditions | Glycogen Storage Disease Type II-Pompe's Disease |
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| Interventions | Avalglucosidase alfa (GZ402666), Alglucosidase alfa (GZ419829) (Drug) |
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| Dates | start 2017-10-12, primary completion 2019-09-30, completion 2027-08-10 (estimated), first posted 2017-01-12, last updated 2026-01-30 |
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| Locations | 12 sites in United States, France, Japan, Taiwan, United Kingdom |
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Related Papers Related Patents Related Grants Related Experts
All trials for Glycogen Storage Disease Type II-Pompe's Disease All trials of Avalglucosidase alfa (GZ402666) All trials of Alglucosidase alfa (GZ419829)
-Summary
This is a multi-stage, phase 2, open-label, multicenter, multinational, ascending dose cohort, repeated intravenous (IV) infusion study of avalglucosidase alfa in pediatric patients with Infantile-Onset Pompe Disease (IOPD) who have been previously treated with alglucosidase alfa for a minimum of 6 months immediately prior to study entry and have demonstrated clinical decline or unsatisfactory clinical response.
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+Detailed description
The duration of the study for each participant will be up to 9 years and 4 months that will consist 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 a 462-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.
+Arms and interventions
| Arm | Type | Interventions | Description |
|---|
| Cohort 1: Avalglucosidase Alfa 20 mg/kg | Experimental | Drug: Avalglucosidase alfa (GZ402666) | 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). |
| Cohort 2: Avalglucosidase Alfa 40 mg/kg | Experimental | Drug: Avalglucosidase alfa (GZ402666) | 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. |
| Cohort 3a: Avalglucosidase Alfa 40 mg//kg | Experimental | Drug: Avalglucosidase alfa (GZ402666) | 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. |
| Cohort 3b: Alglucosidase Alfa in PAP | Experimental | Drug: Avalglucosidase alfa (GZ402666); Drug: Alglucosidase alfa (GZ419829) | 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. |
- Avalglucosidase alfa (GZ402666) (Drug), also known as Nexviazyme: Pharmaceutical form: powder for concentrate for solution for infusion,
Route of administration: IV
- Alglucosidase alfa (GZ419829) (Drug), also known as Myozyme®, Lumizyme®: Pharmaceutical form: powder for concentrate for solution for infusion,
Route of administration: IV
+Outcome measures
Primary outcomes
- PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) [From Baseline to Week 25]: 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) [From Baseline to Week 25]: 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 outcomes
- PAP: Number of Participants With Anti-drug Antibody (ADA) Response [From Baseline to Week 25]: 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 [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]: Cmax is the maximum observed plasma concentration.
- PAP: Pharmacokinetic Parameter: Time to Achieve Maximum Observed Plasma Concentration (Tmax) of Avalglucosidase Alfa [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]: 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 [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]: 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 [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]: 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 [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]: 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 [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]: 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 [Baseline, 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 [Baseline, 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 [Baseline, 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 [Baseline, 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 [Baseline, 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 [Baseline, 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 [Baseline, 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 [Baseline, 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 [Baseline, 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 [Up to 9 years and 4 months]: Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (August 2028).
- ETP: Number of Participants With Infusion-associated Reactions [Up to 9 years and 4 months]: Data for this outcome measure will be reported at the time of anticipated last participant last visit results posting (August 2028).
+Eligibility
Sex: All, ages: 6 Months to 17 Years, accepts healthy volunteers
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:
Participants are excluded from the study if any of the following criteria apply:
* 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.
+Posted results
Participant flow
| Milestone | 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 |
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| Started | 6 | 5 | 5 | 6 |
| Treated | 6 | 5 | 5 | 6 |
| Completed | 6 | 5 | 5 | 6 |
| Not completed | 0 | 0 | 0 | 0 |
Outcome results
- PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) (Primary), Count of participants, Participants: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg 5; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 5; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 5; PAP: Cohort 3b: Alglucosidase Alfa 5
- PAP: Number of Participants With Infusion-associated Reactions (IARs) (Primary), Count of participants, Participants: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg 0; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 2; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 1; PAP: Cohort 3b: Alglucosidase Alfa 1
- PAP: Number of Participants With Anti-drug Antibody (ADA) Response (Secondary), Count of participants, Participants: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg 0; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 0; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 1; PAP: Cohort 3b: Alglucosidase Alfa 2
- PAP: Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa (Secondary), Mean, nanograms per milliliter: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg 189000 +/- 56700; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 403000 +/- 171000; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 250000 +/- 45100
- PAP: Pharmacokinetic Parameter: Time to Achieve Maximum Observed Plasma Concentration (Tmax) of Avalglucosidase Alfa (Secondary), Median, hours: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg 4.43 (3.90 to 5.33); PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 7.00 (6.00 to 7.25); PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 6.83 (6.65 to 7.22)
- 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 (Secondary), Mean, nanograms*hours per milliliter: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg 923000 +/- 352000; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 2630000 +/- 972000; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 1720000 +/- 255000
- PAP: Pharmacokinetic Parameter: Terminal Half-life (t1/2) of Avalglucosidase Alfa (Secondary), Mean, hours: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg 0.703 +/- 0.291; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 1.15 +/- 0.523; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 0.806 +/- 0.248
- PAP: Pharmacokinetic Parameter: Clearance (CL) of Avalglucosidase Alfa (Secondary), Mean, milliliters per hours: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg 673 +/- 222; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 562 +/- 152; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 529 +/- 150
- PAP: Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Avalglucosidase Alfa (Secondary), Mean, milliliters: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg 3550 +/- 927; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 4500 +/- 882; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 4300 +/- 1420
- PAP: Change From Baseline in Gross Motor Function Measure-88 (GMFM-88) Test Scores at Week 25 (Secondary), Mean, percentage of total score: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg 6.50 +/- 22.24; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 9.80 +/- 13.99; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 11.00 +/- 10.80; PAP: Cohort 3b: Alglucosidase Alfa 17.00 +/- 8.44
- PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 (Secondary), Count of participants, Participants: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg 1; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 1; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 2; PAP: Cohort 3b: Alglucosidase Alfa 3
- 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 (Secondary), Mean, score on a scale: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg 6.19 +/- 10.55; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 2.12 +/- 4.04; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 2.60 +/- 1.72; PAP: Cohort 3b: Alglucosidase Alfa 5.20 +/- 5.95
- PAP: Change From Baseline in Quick Motor Function Test (QMFT) Scores at Week 25 (Secondary), Mean, score on a scale: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg -0.17 +/- 4.45; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 3.20 +/- 4.55; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 4.25 +/- 3.30; PAP: Cohort 3b: Alglucosidase Alfa 5.17 +/- 4.54
- PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25 (Secondary), Mean, Z-score: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg -1.10 +/- 1.07; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 0.13 +/- 2.39; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg -0.78 +/- 0.70; PAP: Cohort 3b: Alglucosidase Alfa -0.43 +/- 0.92
- PAP: Change From Baseline in Eyelid Position Measurements: Interpalpebral Fissure Distance (IPFD) - Left Non-Flash and Right Non-Flash at Week 25 (Secondary), Mean, millimeters: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg -0.67 +/- 1.54; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 1.30 +/- 1.48; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 1.30 +/- 0.76; PAP: Cohort 3b: Alglucosidase Alfa -0.50 +/- 0.77
- PAP: Change From Baseline in Eyelid Position Measurements: Left and Right Margin Reflex Distance (MRD) at Week 25 (Secondary), Mean, millimeters: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg -0.08 +/- 1.53; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg -0.38 +/- 0.85; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 0.88 +/- 1.11; PAP: Cohort 3b: Alglucosidase Alfa 0.08 +/- 0.74
- PAP: Change From Baseline in Eyelid Position Measurements Assessed by Margin Pupil Distance (MPD) - Left Non-Flash and Right Non-Flash at Week 25 (Secondary), Mean, millimeters: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg -0.83 +/- 1.44; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg 0.75 +/- 1.19; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg 0.40 +/- 0.42; PAP: Cohort 3b: Alglucosidase Alfa -0.50 +/- 0.32
- PAP: Change From Baseline in Creatine Kinase Value at Week 25 (Secondary), Mean, international units per liters: PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg -208.67 +/- 382.34; PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg -476.60 +/- 467.20; PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg -421.40 +/- 413.39; PAP: Cohort 3b: Alglucosidase Alfa -1.33 +/- 51.20
- ETP: Number of Participants With Treatment Emergent Adverse Events, Serious Treatment Emergent Adverse Events, and Adverse Event of Special Interest (Secondary)
- ETP: Number of Participants With Infusion-associated Reactions (Secondary)
Adverse events
Time frame: From Day 1 to Week 25 in PAP and from Week 26 to 102 in ETP. Safety data were planned to be collected and analyzed for pooled population of participants who received avalglucosidase alfa 40 mg/kg (Cohorts 2 and 3a of PAP) in ETP. AE data collection is still ongoing and will be updated upon study completion.
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|
| PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | 0/6 (0.0%) | 1/6 (16.7%) | 5/6 (83.3%) |
| PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | 0/5 (0.0%) | 3/5 (60.0%) | 5/5 (100.0%) |
| PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | 0/5 (0.0%) | 0/5 (0.0%) | 5/5 (100.0%) |
| PAP: Cohort 3b: Alglucosidase Alfa | 0/6 (0.0%) | 2/6 (33.3%) | 4/6 (66.7%) |
| ETP: Avalglucosidase Alfa 20 mg/kg | 0/6 (0.0%) | 4/6 (66.7%) | 6/6 (100.0%) |
| Pooled Arm ETP: Avalglucosidase Alfa 40 mg/kg | 0/10 (0.0%) | 2/10 (20.0%) | 7/10 (70.0%) |
| Alglucosidase Alfa in PAP Then Avalglucosidase Alfa 40 mg/kg in ETP | 0/3 (0.0%) | 1/3 (33.3%) | 3/3 (100.0%) |
Serious adverse events by term
| Term | Organ system | PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Cohort 3b: Alglucosidase Alfa | ETP: Avalglucosidase Alfa 20 mg/kg | Pooled Arm ETP: Avalglucosidase Alfa 40 mg/kg | Alglucosidase Alfa in PAP Then Avalglucosidase Alfa 40 mg/kg in ETP |
|---|
| Atrial Thrombosis | Cardiac disorders | 0/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Tympanic Membrane Perforation | Ear and labyrinth disorders | 0/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Eyelid Ptosis | Eye disorders | 0/6 | 2/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Strabismus | Eye disorders | 0/6 | 0/5 | 0/5 | 0/6 | 0/6 | 1/10 | 0/3 |
| Pyrexia | General disorders | 0/6 | 1/5 | 0/5 | 0/6 | 0/6 | 1/10 | 0/3 |
| Gastroenteritis | Infections and infestations | 0/6 | 0/5 | 0/5 | 0/6 | 0/6 | 1/10 | 0/3 |
| Influenza | Infections and infestations | 0/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Lung Infection Pseudomonal | Infections and infestations | 0/6 | 0/5 | 0/5 | 1/6 | 0/6 | 0/10 | 0/3 |
| Otitis Media | Infections and infestations | 0/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Pneumonia | Infections and infestations | 0/6 | 0/5 | 0/5 | 1/6 | 2/6 | 1/10 | 0/3 |
| Respiratory Tract Infection Viral | Infections and infestations | 1/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Urinary Tract Infection | Infections and infestations | 0/6 | 0/5 | 0/5 | 1/6 | 0/6 | 0/10 | 0/3 |
| Femur Fracture | Injury, poisoning and procedural complications | 0/6 | 0/5 | 0/5 | 0/6 | 0/6 | 0/10 | 1/3 |
| Joint Dislocation | Injury, poisoning and procedural complications | 0/6 | 0/5 | 0/5 | 1/6 | 0/6 | 0/10 | 0/3 |
| Post Procedural Haemorrhage | Injury, poisoning and procedural complications | 0/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Device Malfunction | Product Issues | 0/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Adenoidal Hypertrophy | Respiratory, thoracic and mediastinal disorders | 0/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Lung Consolidation | Respiratory, thoracic and mediastinal disorders | 0/6 | 0/5 | 0/5 | 1/6 | 0/6 | 0/10 | 0/3 |
| Respiratory Distress | Respiratory, thoracic and mediastinal disorders | 0/6 | 1/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Tonsillar Hypertrophy | Respiratory, thoracic and mediastinal disorders | 0/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
Other adverse events by term
| Term | Organ system | PAP: Cohort 1: Avalglucosidase Alfa 20 mg/kg | PAP: Cohort 2: Avalglucosidase Alfa 40 mg/kg | PAP: Cohort 3a: Avalglucosidase Alfa 40 mg/kg | PAP: Cohort 3b: Alglucosidase Alfa | ETP: Avalglucosidase Alfa 20 mg/kg | Pooled Arm ETP: Avalglucosidase Alfa 40 mg/kg | Alglucosidase Alfa in PAP Then Avalglucosidase Alfa 40 mg/kg in ETP |
|---|
| Lymph Node Pain | Blood and lymphatic system disorders | 0/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Neutropenia | Blood and lymphatic system disorders | 0/6 | 1/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Pericardial Effusion | Cardiac disorders | 1/6 | 0/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Cerumen Impaction | Ear and labyrinth disorders | 0/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Deafness | Ear and labyrinth disorders | 1/6 | 0/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Ear Pain | Ear and labyrinth disorders | 0/6 | 1/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Excessive Cerumen Production | Ear and labyrinth disorders | 1/6 | 0/5 | 0/5 | 1/6 | 1/6 | 0/10 | 0/3 |
| Middle Ear Effusion | Ear and labyrinth disorders | 0/6 | 0/5 | 1/5 | 1/6 | 0/6 | 0/10 | 0/3 |
| Otorrhoea | Ear and labyrinth disorders | 1/6 | 0/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Conjunctivochalasis | Eye disorders | 0/6 | 1/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Eye Discharge | Eye disorders | 0/6 | 0/5 | 1/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Eye Irritation | Eye disorders | 0/6 | 0/5 | 2/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Keratopathy | Eye disorders | 0/6 | 0/5 | 0/5 | 0/6 | 0/6 | 1/10 | 0/3 |
| Lacrimation Increased | Eye disorders | 0/6 | 0/5 | 1/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Abdominal Hernia | Gastrointestinal disorders | 0/6 | 0/5 | 0/5 | 1/6 | 0/6 | 0/10 | 0/3 |
| Abdominal Pain | Gastrointestinal disorders | 0/6 | 1/5 | 1/5 | 0/6 | 1/6 | 1/10 | 0/3 |
| Aphthous Ulcer | Gastrointestinal disorders | 0/6 | 0/5 | 1/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Constipation | Gastrointestinal disorders | 0/6 | 1/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Dental Caries | Gastrointestinal disorders | 0/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Diarrhoea | Gastrointestinal disorders | 0/6 | 1/5 | 2/5 | 0/6 | 1/6 | 1/10 | 0/3 |
| Dysphagia | Gastrointestinal disorders | 0/6 | 0/5 | 0/5 | 0/6 | 0/6 | 1/10 | 0/3 |
| Faeces Soft | Gastrointestinal disorders | 0/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Loose Tooth | Gastrointestinal disorders | 1/6 | 0/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Mucous Stools | Gastrointestinal disorders | 0/6 | 0/5 | 0/5 | 1/6 | 0/6 | 0/10 | 0/3 |
| Nausea | Gastrointestinal disorders | 0/6 | 0/5 | 1/5 | 1/6 | 1/6 | 0/10 | 0/3 |
| Regurgitation | Gastrointestinal disorders | 0/6 | 1/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Teething | Gastrointestinal disorders | 0/6 | 0/5 | 0/5 | 1/6 | 0/6 | 0/10 | 0/3 |
| Toothache | Gastrointestinal disorders | 1/6 | 1/5 | 0/5 | 0/6 | 0/6 | 1/10 | 0/3 |
| Vomiting | Gastrointestinal disorders | 0/6 | 1/5 | 2/5 | 3/6 | 1/6 | 2/10 | 0/3 |
| Asthenia | General disorders | 0/6 | 0/5 | 1/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Catheter Site Oedema | General disorders | 0/6 | 1/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Device Related Thrombosis | General disorders | 0/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Fatigue | General disorders | 0/6 | 0/5 | 1/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Feeling Hot | General disorders | 0/6 | 0/5 | 1/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Infusion Site Swelling | General disorders | 0/6 | 1/5 | 0/5 | 0/6 | 0/6 | 1/10 | 0/3 |
| Injection Site Pain | General disorders | 1/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Malaise | General disorders | 0/6 | 0/5 | 1/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Oedema Peripheral | General disorders | 1/6 | 0/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Pyrexia | General disorders | 2/6 | 1/5 | 2/5 | 1/6 | 2/6 | 2/10 | 0/3 |
| Bronchitis | Infections and infestations | 1/6 | 0/5 | 0/5 | 0/6 | 2/6 | 0/10 | 0/3 |
| Bronchitis Viral | Infections and infestations | 1/6 | 0/5 | 0/5 | 0/6 | 0/6 | 1/10 | 0/3 |
| Conjunctivitis | Infections and infestations | 1/6 | 0/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Enterovirus Infection | Infections and infestations | 1/6 | 0/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Fungal Skin Infection | Infections and infestations | 0/6 | 0/5 | 0/5 | 1/6 | 0/6 | 0/10 | 1/3 |
| Gastroenteritis | Infections and infestations | 0/6 | 1/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Hand-Foot-And-Mouth Disease | Infections and infestations | 0/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Influenza | Infections and infestations | 1/6 | 0/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Lower Respiratory Tract Infection | Infections and infestations | 0/6 | 0/5 | 0/5 | 1/6 | 0/6 | 0/10 | 0/3 |
| Lung Infection | Infections and infestations | 0/6 | 0/5 | 0/5 | 0/6 | 0/6 | 0/10 | 1/3 |
| Lung Infection Pseudomonal | Infections and infestations | 0/6 | 0/5 | 0/5 | 1/6 | 0/6 | 0/10 | 0/3 |
| Nail Infection | Infections and infestations | 0/6 | 0/5 | 0/5 | 0/6 | 0/6 | 0/10 | 1/3 |
| Nasopharyngitis | Infections and infestations | 0/6 | 0/5 | 0/5 | 0/6 | 0/6 | 1/10 | 0/3 |
| Otitis Externa | Infections and infestations | 0/6 | 0/5 | 0/5 | 0/6 | 1/6 | 0/10 | 0/3 |
| Otitis Media | Infections and infestations | 1/6 | 0/5 | 0/5 | 1/6 | 2/6 | 0/10 | 1/3 |
| Parainfluenzae Virus Infection | Infections and infestations | 0/6 | 0/5 | 0/5 | 1/6 | 0/6 | 0/10 | 0/3 |
| Pneumonia | Infections and infestations | 1/6 | 0/5 | 0/5 | 0/6 | 0/6 | 0/10 | 0/3 |
| Pneumonia Pseudomonal | Infections and infestations | 0/6 | 0/5 | 0/5 | 1/6 | 0/6 | 0/10 | 0/3 |
| Rhinitis | Infections and infestations | 0/6 | 0/5 | 0/5 | 1/6 | 1/6 | 0/10 | 0/3 |
| Sepsis | Infections and infestations | 0/6 | 0/5 | 0/5 | 0/6 | 0/6 | 1/10 | 0/3 |
| Stoma Site Infection | Infections and infestations | 0/6 | 0/5 | 0/5 | 1/6 | 0/6 | 0/10 | 0/3 |
72 more terms not shown.
+Locations (12)
| Facility | City | Country | Status |
|---|
| Regional Medical Genetics Center of New York Site Number : 8400002 | Valhalla, New York | United States | |
| Duke University Medical Center Site Number : 8400001 | Durham, North Carolina | United States | |
| Seattle Childrens Hospital and Regional Medical Center- Site Number : 8400005 | Seattle, Washington | United States | |
| Investigational Site Number : 2500004 | Nantes | France | |
| Investigational Site Number : 2500003 | Paris | France | |
| Investigational Site Number : 2500002 | Paris | France | |
| Investigational Site Number : 2500001 | Tours | France | |
| Investigational Site Number : 3920001 | Fuchu-shi, Tokyo | Japan | |
| Investigational Site Number : 3920002 | Fuchu-shi, Tokyo | Japan | |
| Investigational Site Number : 1580001 | Hsinchu | Taiwan | |
| Investigational Site Number : 8260001 | London, London, City of | United Kingdom | |
| Investigational Site Number : 8260002 | Manchester | United Kingdom | |
+Publications
- Results publication: Kronn D, Davison J, Broomfield A, Brassier A, Labarthe F, Hahn SH, Kumada S, Ohki H, Prakalapakorn SG, Wilson C, Haack KA, Huynh-Ba O, Richards S, Sparks S, Tammireddy S, Zhou T, Chien YH, Kishnani PS; Mini-COMET investigators. The Mini-COMET Clinical Trial: Safety and Efficacy of Avalglucosidase Alfa after 97 Weeks of Treatment in Children with Infantile-Onset Pompe Disease Previously Treated with Alglucosidase Alfa. J Pediatr. 2025 Oct;285:114664. doi: 10.1016/j.jpeds.2025.114664. Epub 2025 May 29. PMID 40449831
- Results publication: Kishnani PS, Kronn D, Brassier A, Broomfield A, Davison J, Hahn SH, Kumada S, Labarthe F, Ohki H, Pichard S, Prakalapakorn SG, Haack KA, Kittner B, Meng X, Sparks S, Wilson C, Zaher A, Chien YH; Mini-COMET Investigators. Safety and efficacy of avalglucosidase alfa in individuals with infantile-onset Pompe disease enrolled in the phase 2, open-label Mini-COMET study: The 6-month primary analysis report. Genet Med. 2023 Feb;25(2):100328. doi: 10.1016/j.gim.2022.10.010. Epub 2022 Dec 21. PMID 36542086
+Study documents
+Investigators
- Clinical Sciences & Operations, Study director, Sanofi
+Funding