Study to Compare the Efficacy and Safety of Enzyme Replacement Therapies Avalglucosidase Alfa and Alglucosidase Alfa Administered Every Other Week in Patients With Late-onset Pompe Disease Who Have Not Been Previously Treated for Pompe Disease

NCT ID: NCT02782741

Last Updated: 2024-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-02
• Study Completion Date: 2023-05-31

Brief Summary

Primary Objective:

To determine the effect of avalglucosidase alfa treatment on respiratory muscle strength measured by percent (%) predicted forced vital capacity (FVC) in the upright position, as compared to alglucosidase alfa.

Secondary Objective:

To determine the safety and effect of avalglucosidase alfa treatment on functional endurance (6-minute walk test, inspiratory muscle strength (maximum inspiratory pressure), expiratory muscle strength (maximum expiratory pressure), lower extremity muscle strength (hand-held dynamometry), motor function (Quick Motor Function Test), and health-related quality of life (Short Form-12).

Detailed Description

The duration of the study per participant will be up to approximately 6 years that will consist of a 14-day screening period (may be extended up to 8 weeks in pre-specified situations), a 49-week blinded treatment period (except for the subgroup of pediatric patients aged 3 to less than (<) 18 years enrolling directly in the open-label long-term follow-up phase), a 240-week open-label treatment period, and a 4-week post-treatment observation period.

Conditions

Glycogen Storage Disease Type II;Pompe's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

avalglucosidase alfa (GZ402666)

Administered intravenously every 2 weeks

Group Type: EXPERIMENTAL

Avalglucosidase alfa (GZ402666)

Intervention Type: DRUG

Pharmaceutical form: powder for concentrate for solution for infusion Route of administration: intravenous

alglucosidase alfa (GZ419829)

Administered intravenously every 2 weeks

Group Type: ACTIVE_COMPARATOR

Alglucosidase alfa (GZ419829)

Intervention Type: DRUG

Pharmaceutical form: powder for concentrate for solution for infusion Route of administration: intravenous

Interventions

Avalglucosidase alfa (GZ402666)

Pharmaceutical form: powder for concentrate for solution for infusion Route of administration: intravenous

Intervention Type: DRUG

Alglucosidase alfa (GZ419829)

Pharmaceutical form: powder for concentrate for solution for infusion Route of administration: intravenous

Intervention Type: DRUG

Other Intervention Names

Myozyme; Lumizyme

Eligibility Criteria

Inclusion Criteria

• The participant has confirmed acid alpha-glucosidase (GAA) enzyme deficiency from any tissue source and/or 2 confirmed GAA gene mutations.
• The participant must provide signed, informed consent prior to performing any study related procedures. Consent of a legally authorized guardian(s) is (are) required for legally minor participant as defined by local regulation. If the participant is legally minor, signed written consent shall be obtained from parent(s)/legal guardian and assent obtained from participants, if applicable.

Exclusion Criteria

• The participant is <3 years of age.
• The participant has known Pompe specific cardiac hypertrophy.
• The participant is wheelchair dependent.
• The participant is not able to ambulate 40 meters (approximately 130 feet) without stopping and without an assistive device.
• The participant requires invasive-ventilation (non-invasive ventilation is allowed).
• The participant is not able to successfully perform repeated forced vital capacity (FVC) measurements in upright position of greater than or equal to 30% predicted and less than or equal to 85% predicted.
• The participant (and participant's legal guardian if participant is legally minor as defined by local regulation) is (are) not able to comply with the clinical protocol.
• The participant has had previous treatment with alglucosidase alfa or any investigational therapy for Pompe disease.
• The participant has prior or current use of immune tolerance induction therapy.
• The participant, if female and of childbearing potential, has a positive pregnancy test (beta-human chorionic gonadotropin) at baseline.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

• Minimum Eligible Age: 3 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genzyme, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 8400015

Phoenix, Arizona, United States

Investigational Site Number 8400020

Los Angeles, California, United States

Investigational Site Number 8400011

Orange, California, United States

Investigational Site Number 8400017

Stanford, California, United States

Investigational Site Number 8400016

Gainesville, Florida, United States

Investigational Site Number 8400007

Decatur, Georgia, United States

Investigational Site Number 8400023

Chicago, Illinois, United States

Investigational Site Number 8400002

Iowa City, Iowa, United States

Investigational Site Number 8400012

Kansas City, Kansas, United States

Investigational Site Number 8400010

Boston, Massachusetts, United States

Investigational Site Number 8400001

Detroit, Michigan, United States

Investigational Site Number 8400019

Minneapolis, Minnesota, United States

Investigational Site Number 8400026

Great Neck, New York, United States

Investigational Site Number 8400008

Valhalla, New York, United States

Investigational Site Number 8400006

Durham, North Carolina, United States

Investigational Site Number 8400009

Cincinnati, Ohio, United States

Investigational Site Number 8400014

Portland, Oregon, United States

Investigational Site Number 8400025

Pittsburgh, Pennsylvania, United States

Investigational Site Number 8400018

Salt Lake City, Utah, United States

Investigational Site Number 8400005

Fairfax, Virginia, United States

Investigational Site Number 8400024

Morgantown, West Virginia, United States

Investigational Site Number 0320001

Caba, , Argentina

Investigational Site Number 0360001

Auchenflower, , Australia

Investigational Site Number 0400001

Vienna, , Austria

Investigational Site Number 0560003

Brussels, , Belgium

Investigational Site Number 0560001

Leuven, , Belgium

Investigational Site Number 0760004

Brasília, , Brazil

Investigational Site Number 0760001

São Paulo, , Brazil

Investigational Site Number 1240003

Hamilton, , Canada

Investigational Site Number 1240002

Montreal, , Canada

Investigational Site Number 2030001

Prague, , Czechia

Investigational Site Number 2080003

København Ø, , Denmark

Investigational Site Number 2500008

Angers, , France

Investigational Site Number 2500007

Bordeaux, , France

Investigational Site Number 2500011

Brest, , France

Investigational Site Number 2500004

Bron, , France

Investigational Site Number 2500010

Clermont-Ferrand, , France

Investigational Site Number 2500005

Lille, , France

Investigational Site Number 2500006

Marseille, , France

Investigational Site Number 2500001

Paris, , France

Investigational Site Number 2760006

Bochum, , Germany

Investigational Site Number 2760001

Mainz, , Germany

Investigational Site Number 2760003

München, , Germany

Investigational Site Number 2760002

Münster, , Germany

Investigational Site Number 3480001

Budapest, , Hungary

Investigational Site Number 3800006

Brescia, , Italy

Investigational Site Number 3800001

Messina, , Italy

Investigational Site Number 3800002

Milan, , Italy

Investigational Site Number 3800007

Napoli, , Italy

Investigational Site Number 3800003

Torino, , Italy

Investigational Site Number 3920002

Kodaira-Shi, , Japan

Investigational Site Number 4840001

México, , Mexico

Investigational Site Number 5280001

Rotterdam, , Netherlands

Investigational Site Number 6160001

Warsaw, , Poland

Investigational Site Number 6200001

Braga, , Portugal

Investigational Site Number 6430001

Moscow, , Russia

Investigational Site Number 4100001

Seoul, , South Korea

Investigational Site Number 4100002

Seoul, , South Korea

Investigational Site Number 7240002

Barcelona, , Spain

Investigational Site Number 7240003

Barcelona, , Spain

Investigational Site Number 7560002

Zurich, , Switzerland

Investigational Site Number 1580001

Taipei, , Taiwan

Investigational Site Number 7920001

Ankara, , Turkey (Türkiye)

Investigational Site Number 7920002

Istanbul, , Turkey (Türkiye)

Investigational Site Number 8260005

Birmingham, , United Kingdom

Investigational Site Number 8260002

Cambridge, , United Kingdom

Investigational Site Number 8260001

London, , United Kingdom

Investigational Site Number 8260004

Newcastle upon Tyne, , United Kingdom

Investigational Site Number 8260003

Salford, , United Kingdom

Countries

United States; Argentina; Australia; Austria; Belgium; Brazil; Canada; Czechia; Denmark; France; Germany; Hungary; Italy; Japan; Mexico; Netherlands; Poland; Portugal; Russia; South Korea; Spain; Switzerland; Taiwan; Turkey (Türkiye); United Kingdom

References

Kishnani PS, Diaz-Manera J, Illarioshkin S, van der Ploeg AT, Clemens PR, Day JW, Toscano A, Kushlaf H, Ladha S, Attarian S, Carvalho G, Kostera-Pruszczyk A, Erdem-Ozdamar S, Goker-Alpan O, Mozaffar T, Straub V, Roberts M, Haack KA, Huynh-Ba O, Tammireddy S, Periquet M, Thibault N, Zhou T, Dimachkie MM, Schoser B; COMET Investigator Group. Efficacy and safety of avalglucosidase alfa in patients with late-onset Pompe disease after 145 weeks of treatment during the COMET trial. J Neurol. 2025 Aug 16;272(9):581. doi: 10.1007/s00415-025-13266-y.

Reference Type: DERIVED

PMID: 40817977 (View on PubMed)

Dimachkie MM, Kishnani PS, Ivanescu C, Flore G, Gwaltney C, van der Beek NAME, Hamed A, An Haack K, Pollissard L, Baranowski E, Sparks SE, DasMahapatra P; for COMET Study Group. Measurement Properties of 2 Novel PROs, the Pompe Disease Symptom Scale and Pompe Disease Impact Scale, in the COMET Study. Neurol Clin Pract. 2023 Oct;13(5):e200181. doi: 10.1212/CPJ.0000000000200181. Epub 2023 Aug 8.

Reference Type: DERIVED

PMID: 37559825 (View on PubMed)

Kishnani PS, Diaz-Manera J, Toscano A, Clemens PR, Ladha S, Berger KI, Kushlaf H, Straub V, Carvalho G, Mozaffar T, Roberts M, Attarian S, Chien YH, Choi YC, Day JW, Erdem-Ozdamar S, Illarioshkin S, Goker-Alpan O, Kostera-Pruszczyk A, van der Ploeg AT, An Haack K, Huynh-Ba O, Tammireddy S, Thibault N, Zhou T, Dimachkie MM, Schoser B; COMET Investigator Group. Efficacy and Safety of Avalglucosidase Alfa in Patients With Late-Onset Pompe Disease After 97 Weeks: A Phase 3 Randomized Clinical Trial. JAMA Neurol. 2023 Jun 1;80(6):558-567. doi: 10.1001/jamaneurol.2023.0552.

Reference Type: DERIVED

PMID: 37036722 (View on PubMed)

Diaz-Manera J, Kishnani PS, Kushlaf H, Ladha S, Mozaffar T, Straub V, Toscano A, van der Ploeg AT, Berger KI, Clemens PR, Chien YH, Day JW, Illarioshkin S, Roberts M, Attarian S, Borges JL, Bouhour F, Choi YC, Erdem-Ozdamar S, Goker-Alpan O, Kostera-Pruszczyk A, Haack KA, Hug C, Huynh-Ba O, Johnson J, Thibault N, Zhou T, Dimachkie MM, Schoser B; COMET Investigator Group. Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial. Lancet Neurol. 2021 Dec;20(12):1012-1026. doi: 10.1016/S1474-4422(21)00241-6.

Reference Type: DERIVED

PMID: 34800399 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-000942-77

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1178-4806

Identifier Type: OTHER

Identifier Source: secondary_id

EFC14028

Identifier Type: -

Identifier Source: org_study_id