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

NCT03019406 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: ACT14132U1111-1179-46162016-003475-21
• Study Type: interventional
• Target: 22
• Locations: 5 countries
• Sites: 12

Brief 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.

Conditions

Glycogen Storage Disease Type II-Pompe's Disease

Outcome Measures

Primary Outcomes (2)

• 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.

  From Baseline to Week 25

• 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.

  From Baseline to Week 25

Secondary Outcomes (18)

• PAP: Number of Participants With Anti-drug Antibody (ADA) Response

  From Baseline to Week 25

• 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

• 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

• 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

• 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

Study Arms (4)

Cohort 1: Avalglucosidase Alfa 20 mg/kg

EXPERIMENTAL

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).

Drug: Avalglucosidase alfa (GZ402666)

Cohort 2: Avalglucosidase Alfa 40 mg/kg

EXPERIMENTAL

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.

Drug: Avalglucosidase alfa (GZ402666)

Cohort 3a: Avalglucosidase Alfa 40 mg//kg

EXPERIMENTAL

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.

Drug: Avalglucosidase alfa (GZ402666)

Cohort 3b: Alglucosidase Alfa in PAP

EXPERIMENTAL

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.

Drug: Avalglucosidase alfa (GZ402666); Drug: Alglucosidase alfa (GZ419829)

Interventions

Avalglucosidase alfa (GZ402666) DRUG

Pharmaceutical form: powder for concentrate for solution for infusion, Route of administration: IV

Also known as: Nexviazyme

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

Alglucosidase alfa (GZ419829) DRUG

Pharmaceutical form: powder for concentrate for solution for infusion, Route of administration: IV

Also known as: Myozyme®, Lumizyme®

Cohort 3b: Alglucosidase Alfa in PAP

Eligibility Criteria

• Age: 6 Months - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (12)

Regional Medical Genetics Center of New York Site Number : 8400002

Valhalla, New York, 10595, United States

Location

Duke University Medical Center Site Number : 8400001

Durham, North Carolina, 27710-4000, United States

Location

Seattle Childrens Hospital and Regional Medical Center- Site Number : 8400005

Seattle, Washington, 98040, United States

Location

Investigational Site Number : 2500004

Nantes, 44093, France

Location

Investigational Site Number : 2500003

Paris, 75015, France

Location

Investigational Site Number : 2500002

Paris, 75019, France

Location

Investigational Site Number : 2500001

Tours, 37044, France

Location

Investigational Site Number : 3920001

Fuchu-shi, Tokyo, 183-0042, Japan

Location

Investigational Site Number : 3920002

Fuchu-shi, Tokyo, 183-8561, Japan

Location

Investigational Site Number : 1580001

Hsinchu, 30059, Taiwan

Location

Investigational Site Number : 8260001

London, London, City of, WC1N 3JH, United Kingdom

Location

Investigational Site Number : 8260002

Manchester, M13 9WL, United Kingdom

Location

Related Publications (2)

• 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 DERIVED

• 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 DERIVED

MeSH Terms

Interventions

GAA protein, human

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Genzyme, a Sanofi Company

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2016
• First Posted: January 12, 2017
• Study Start: October 12, 2017
• Primary Completion: September 30, 2019
• Study Completion (Estimated): August 10, 2027
• Last Updated: January 30, 2026
• Results First Posted: November 22, 2021

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

TW (1); US (3); JP (2); GB (2); FR (4)