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

• Register: ClinicalTrials.gov
• Last refreshed on: 10 July 2023
• Main ID: NCT03019406
• Date of registration: 20/12/2016
• Prospective Registration: Yes
• Primary sponsor: Genzyme, a Sanofi Company
• Public 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 Mini-COMET
• Scientific 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
• Date of first enrolment: October 12, 2017
• Target sample size: 22
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT03019406
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

France, Japan, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Sciences & Operations
• Affiliation: Sanofi

Key inclusion & exclusion 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.



Age minimum: 6 Months
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Glycogen Storage Disease Type II-Pompe's Disease

Intervention(s)

Drug: Alglucosidase alfa (GZ419829)

Drug: Avalglucosidase alfa (GZ402666)

Primary Outcome(s)

PAP: Number of Participants With Infusion-associated Reactions (IARs) [Time Frame: From Baseline to Week 25]

PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Treatment-emergent Adverse Events, and Adverse Event of Special Interest (AESI) [Time Frame: From Baseline to Week 25]

Secondary Outcome(s)

PAP: Number of Participants in Gross Motor Function Classification System-Expanded and Revised (GMFCS-E and R) Scores at Baseline and Week 25 [Time Frame: Baseline, Week 25]

PAP: Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of Avalglucosidase Alfa [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]

ETP: Number of Participants With Treatment Emergent Adverse Events, Serious Treatment Emergent Adverse Events, and Adverse Event of Special Interest [Time Frame: From Week 26 to Week 371]

PAP: Change From Baseline in Eyelid Position Measurements Assessed by Margin Pupil Distance (MPD) - Left Non-Flash and Right Non-Flash at Week 25 [Time Frame: Baseline, Week 25]

PAP: Pharmacokinetic Parameter: Volume of Distribution at Steady State (Vss) of Avalglucosidase Alfa [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]

PAP: Number of Participants With Anti-drug Antibody (ADA) Response [Time Frame: From Baseline to Week 25]

PAP: Pharmacokinetic Parameter: Terminal Half-life (t1/2) of Avalglucosidase Alfa [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]

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 [Time Frame: Baseline, Week 25]

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 [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]

PAP: Pharmacokinetic Parameter: Clearance (CL) of Avalglucosidase Alfa [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]

PAP: Change From Baseline in Eyelid Position Measurements: Interpalpebral Fissure Distance (IPFD) - Left Non-Flash and Right Non-Flash at Week 25 [Time Frame: Baseline, Week 25]

PAP: Change From Baseline in Eyelid Position Measurements: Left and Right Margin Reflex Distance (MRD) at Week 25 [Time Frame: Baseline, Week 25]

PAP: Echo-Left Ventricular Mass Z-Score (LVM Z-score) M-mode at Baseline, Week 25, and Change From Baseline at Week 25 [Time Frame: Baseline, Week 25]

ETP: Number of Participants With Infusion-associated Reactions [Time Frame: From Week 26 to Week 371]

PAP: Pharmacokinetic Parameter: Time to Achieve Maximum Observed Plasma Concentration (Tmax) of Avalglucosidase Alfa [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]

PAP: Change From Baseline in Creatine Kinase Value at Week 25 [Time Frame: Baseline, Week 25]

PAP: Change From Baseline in Gross Motor Function Measure-88 (GMFM-88) Test Scores at Week 25 [Time Frame: Baseline, Week 25]

PAP: Change From Baseline in Quick Motor Function Test (QMFT) Scores at Week 25 [Time Frame: Baseline, Week 25]

Secondary ID(s)

2016-003475-21

U1111-1179-4616

ACT14132

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 22/11/2021
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03019406