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

NCT02782741 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: EFC140282016-000942-77U1111-1178-4806
• Study Type: interventional
• Target: 101
• Locations: 24 countries
• Sites: 68

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).

Conditions

Glycogen Storage Disease Type II;Pompe's Disease

Outcome Measures

Primary Outcomes (1)

• PAP: Change From Baseline in Percent Predicted FVC in Upright Position at Week 49

  FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Least square (LS) mean and standard error (SE) were derived from mixed model for repeated measure (MMRM) model with baseline FVC \[percent (%) predicted, as continuous\], sex, age (in years at baseline), treatment group, visit, interaction term between treatment group and visit as fixed effects. Percent of predicted FVC = (actual FVC measurement)/(predicted value of FVC) \* 100. After non-inferiority (NI) testing, a test for superiority of avalglucosidase alfa versus alglucosidase alfa was performed with an overall 2-sided 5% level of significance.

  Baseline, Week 49

Secondary Outcomes (9)

• PAP: Change From Baseline in Total Distance Walked During Six-minute Walk Test (6MWT) at Week 49

  Baseline, Week 49

• PAP: Change From Baseline in Percent Predicted Maximal Inspiratory Pressure (MIP) in Upright Position at Week 49

  Baseline, Week 49

• PAP: Change From Baseline in Percent Predicted Maximal Expiratory Pressure (MEP) in Upright Position at Week 49

  Baseline, Week 49

• PAP: Change From Baseline in Lower Extremity Muscle Strength at Week 49 as Assessed by Hand-Held Dynamometry (HHD)

  Baseline, Week 49

• PAP: Change From Baseline in Quick Motor Function Test (QMFT) Total Scores at Week 49

  Baseline, Week 49

Study Arms (2)

avalglucosidase alfa (GZ402666)

EXPERIMENTAL

Administered intravenously every 2 weeks

Drug: Avalglucosidase alfa (GZ402666)

alglucosidase alfa (GZ419829)

ACTIVE COMPARATOR

Administered intravenously every 2 weeks

Drug: Alglucosidase alfa (GZ419829)

Interventions

Avalglucosidase alfa (GZ402666) DRUG

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

avalglucosidase alfa (GZ402666)

Alglucosidase alfa (GZ419829) DRUG

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

Also known as: Myozyme, Lumizyme

alglucosidase alfa (GZ419829)

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (69)

Investigational Site Number 8400015

Phoenix, Arizona, 85013, United States

Location

Investigational Site Number 8400020

Los Angeles, California, 90095, United States

Location

Investigational Site Number 8400011

Orange, California, 92868, United States

Location

Investigational Site Number 8400017

Stanford, California, 94305, United States

Location

Investigational Site Number 8400016

Gainesville, Florida, 32610, United States

Location

Investigational Site Number 8400007

Decatur, Georgia, 30033, United States

Location

Investigational Site Number 8400023

Chicago, Illinois, 60611, United States

Location

Investigational Site Number 8400002

Iowa City, Iowa, 52242, United States

Location

Investigational Site Number 8400012

Kansas City, Kansas, 66160-7321, United States

Location

Investigational Site Number 8400010

Boston, Massachusetts, 02114, United States

Location

Investigational Site Number 8400001

Detroit, Michigan, 48201, United States

Location

Investigational Site Number 8400019

Minneapolis, Minnesota, 55455, United States

Location

Investigational Site Number 8400026

Great Neck, New York, 11020, United States

Location

Investigational Site Number 8400008

Valhalla, New York, 10595, United States

Location

Investigational Site Number 8400006

Durham, North Carolina, 27710, United States

Location

Investigational Site Number 8400009

Cincinnati, Ohio, 45267-0542, United States

Location

Investigational Site Number 8400014

Portland, Oregon, 97239, United States

Location

Investigational Site Number 8400025

Pittsburgh, Pennsylvania, 15213, United States

Location

Investigational Site Number 8400018

Salt Lake City, Utah, 84132, United States

Location

Investigational Site Number 8400005

Fairfax, Virginia, 22030, United States

Location

Investigational Site Number 8400024

Morgantown, West Virginia, 26506, United States

Location

Investigational Site Number 0320001

Caba, C1181ACH, Argentina

Location

Investigational Site Number 0360001

Auchenflower, 4066, Australia

Location

Investigational Site Number 0400001

Vienna, 1090, Austria

Location

Investigational Site Number 0560003

Brussels, 1070, Belgium

Location

Investigational Site Number 0560001

Leuven, 3000, Belgium

Location

Investigational Site Number 0760004

Brasília, 71625-009, Brazil

Location

Investigational Site Number 0760001

São Paulo, 04037-002, Brazil

Location

Investigational Site Number 1240003

Hamilton, L8N 3Z5, Canada

Location

Investigational Site Number 1240002

Montreal, H3A 2B4, Canada

Location

Investigational Site Number 2030001

Prague, 12808, Czechia

Location

Investigational Site Number 2080003

København Ø, 2100, Denmark

Location

Investigational Site Number 2500008

Angers, 49933, France

Location

Investigational Site Number 2500007

Bordeaux, France

Location

Investigational Site Number 2500011

Brest, 29609, France

Location

Investigational Site Number 2500004

Bron, 69677, France

Location

Investigational Site Number 2500010

Clermont-Ferrand, 63003, France

Location

Investigational Site Number 2500005

Lille, 59037, France

Location

Investigational Site Number 2500006

Marseille, 13385, France

Location

Investigational Site Number 2500001

Paris, 75013, France

Location

Investigational Site Number 2760006

Bochum, 44789, Germany

Location

Investigational Site Number 2760001

Mainz, 55131, Germany

Location

Investigational Site Number 2760003

München, 80336, Germany

Location

Investigational Site Number 2760002

Münster, 48149, Germany

Location

Investigational Site Number 3480001

Budapest, 1083, Hungary

Location

Investigational Site Number 3800006

Brescia, 25123, Italy

Location

Investigational Site Number 3800001

Messina, 98125, Italy

Location

Investigational Site Number 3800002

Milan, 20122, Italy

Location

Investigational Site Number 3800007

Napoli, 80131, Italy

Location

Investigational Site Number 3800003

Torino, 10126, Italy

Location

Investigational Site Number 3920002

Kodaira-Shi, Japan

Location

Investigational Site Number 4840001

México, Mexico

Location

Investigational Site Number 5280001

Rotterdam, 3015 GE, Netherlands

Location

Investigational Site Number 6160001

Warsaw, 02-097, Poland

Location

Investigational Site Number 6200001

Braga, 4710-243, Portugal

Location

Investigational Site Number 6430001

Moscow, 125367, Russia

Location

Investigational Site Number 4100001

Seoul, 03080, South Korea

Location

Investigational Site Number 4100002

Seoul, 06273, South Korea

Location

Investigational Site Number 7240002

Barcelona, 08025, Spain

Location

Investigational Site Number 7240003

Barcelona, 08950, Spain

Location

Investigational Site Number 7560002

Zurich, 8091, Switzerland

Location

Investigational Site Number 1580001

Taipei, 10043, Taiwan

Location

Investigational Site Number 7920001

Ankara, 06100, Turkey (Türkiye)

Location

Investigational Site Number 7920002

Istanbul, 34390, Turkey (Türkiye)

Location

Investigational Site Number 8260005

Birmingham, B15 2GW, United Kingdom

Location

Investigational Site Number 8260002

Cambridge, CB2 OQQ, United Kingdom

Location

Investigational Site Number 8260001

London, NW3 2QG, United Kingdom

Location

Investigational Site Number 8260004

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Investigational Site Number 8260003

Salford, M6 8HD, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 40817977 DERIVED

• 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.

  PMID: 37559825 DERIVED

• 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.

  PMID: 37036722 DERIVED

• 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.

  PMID: 34800399 DERIVED

MeSH Terms

Interventions

GAA protein, human

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

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 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2016
• First Posted: May 25, 2016
• Study Start: November 2, 2016
• Primary Completion: March 19, 2020
• Study Completion: May 31, 2023
• Last Updated: April 4, 2024
• Results First Posted: April 8, 2021

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share

Locations

DE (4); US (21); ME (1); BE (2); AU (1); NL (1); PL (1); PT (1); RU (1); ES (2); CH (1); TW (1); TU (2); GB (5); AR (1); KR (2); BR (2); CA (2); HU (1); CZ (1); DK (1); IT (5); JP (1); FR (8)