Clinical trial NCT02782741: 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
Official title: A Phase 3 Randomized, Multicenter, Multinational, Double-blinded Study Comparing the Efficacy and Safety of Repeated Biweekly Infusions of Avalglucosidase Alfa (neoGAA, GZ402666) and Alglucosidase Alfa in Treatment naïve Patients With Late-onset Pompe Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Glycogen Storage Disease Type II;Pompe's Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2016-05-25
Enrollment: 101
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: PAP: Change From Baseline in Percent Predicted FVC in Upright Position at Week 49
timeFrame: Baseline, Week 49
Secondary outcomes:
measure: PAP: Change From Baseline in Total Distance Walked During Six-minute Walk Test (6MWT) at Week 49
timeFrame: Baseline, Week 49
measure: PAP: Change From Baseline in Percent Predicted Maximal Inspiratory Pressure (MIP) in Upright Position at Week 49
timeFrame: Baseline, Week 49
measure: PAP: Change From Baseline in Percent Predicted Maximal Expiratory Pressure (MEP) in Upright Position at Week 49
timeFrame: Baseline, Week 49
measure: PAP: Change From Baseline in Lower Extremity Muscle Strength at Week 49 as Assessed by Hand-Held Dynamometry (HHD)
timeFrame: Baseline, Week 49
measure: PAP: Change From Baseline in Quick Motor Function Test (QMFT) Total Scores at Week 49
timeFrame: Baseline, Week 49
measure: PAP: Change From Baseline in 12-Item Short-Form Health Survey (SF-12): Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores at Week 49
timeFrame: Baseline, Week 49
measure: PAP: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Infusion-Associated Reactions (IARs)
timeFrame: From Baseline up to Week 49
measure: Open-label Period: Number of Participants With TEAEs and IARs
timeFrame: Week 50 to 289 in open-label long-term period
measure: PAP: Percentage of Participants With Treatment-Emergent Antidrug Antibodies (ADA) Response
timeFrame: From Baseline up to Week 49
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Investigational Site Number 8400015
state: Arizona
city: Los Angeles
country: United States
facility: Investigational Site Number 8400020
state: California
city: Orange
country: United States
facility: Investigational Site Number 8400011
state: California
city: Stanford
country: United States
facility: Investigational Site Number 8400017
state: California
city: Gainesville
country: United States
facility: Investigational Site Number 8400016
state: Florida
city: Decatur
country: United States
facility: Investigational Site Number 8400007
state: Georgia
city: Chicago
country: United States
facility: Investigational Site Number 8400023
state: Illinois
city: Iowa City
country: United States
facility: Investigational Site Number 8400002
state: Iowa
city: Kansas City
country: United States
facility: Investigational Site Number 8400012
state: Kansas
city: Boston
country: United States
facility: Investigational Site Number 8400010
state: Massachusetts
city: Detroit
country: United States
facility: Investigational Site Number 8400001
state: Michigan
city: Minneapolis
country: United States
facility: Investigational Site Number 8400019
state: Minnesota
city: Great Neck
country: United States
facility: Investigational Site Number 8400026
state: New York
city: Valhalla
country: United States
facility: Investigational Site Number 8400008
state: New York
city: Durham
country: United States
facility: Investigational Site Number 8400006
state: North Carolina
city: Cincinnati
country: United States
facility: Investigational Site Number 8400009
state: Ohio
city: Portland
country: United States
facility: Investigational Site Number 8400014
state: Oregon
city: Pittsburgh
country: United States
facility: Investigational Site Number 8400025
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Investigational Site Number 8400018
state: Utah
city: Fairfax
country: United States
facility: Investigational Site Number 8400005
state: Virginia
city: Morgantown
country: United States
facility: Investigational Site Number 8400024
state: West Virginia
city: Caba
country: Argentina
facility: Investigational Site Number 0320001
city: Auchenflower
country: Australia
facility: Investigational Site Number 0360001
city: Wien
country: Austria
facility: Investigational Site Number 0400001
city: Bruxelles
country: Belgium
facility: Investigational Site Number 0560003
city: Leuven
country: Belgium
facility: Investigational Site Number 0560001
city: Brasilia
country: Brazil
facility: Investigational Site Number 0760004
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 0760001
city: Hamilton
country: Canada
facility: Investigational Site Number 1240003
city: Montreal
country: Canada
facility: Investigational Site Number 1240002
city: Praha 2
country: Czechia
facility: Investigational Site Number 2030001
city: København Ø
country: Denmark
facility: Investigational Site Number 2080003
city: Angers
country: France
facility: Investigational Site Number 2500008
city: Bordeaux
country: France
facility: Investigational Site Number 2500007
city: Brest Cedex 2
country: France
facility: Investigational Site Number 2500011
city: Bron
country: France
facility: Investigational Site Number 2500004
city: Clermont Ferrand
country: France
facility: Investigational Site Number 2500010
city: Lille
country: France
facility: Investigational Site Number 2500005
city: Marseille Cedex 5
country: France
facility: Investigational Site Number 2500006
city: Paris
country: France
facility: Investigational Site Number 2500001
city: Bochum
country: Germany
facility: Investigational Site Number 2760006
city: Mainz
country: Germany
facility: Investigational Site Number 2760001
city: München
country: Germany
facility: Investigational Site Number 2760003
city: Münster
country: Germany
facility: Investigational Site Number 2760002
city: Budapest
country: Hungary
facility: Investigational Site Number 3480001
city: Brescia
country: Italy
facility: Investigational Site Number 3800006
city: Messina
country: Italy
facility: Investigational Site Number 3800001
city: Milano
country: Italy
facility: Investigational Site Number 3800002
city: Napoli
country: Italy
facility: Investigational Site Number 3800007
city: Torino
country: Italy
facility: Investigational Site Number 3800003
city: Kodaira-Shi
country: Japan
facility: Investigational Site Number 3920002
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 4100001
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 4100002
city: Mexico
country: Mexico
facility: Investigational Site Number 4840001
city: Rotterdam
country: Netherlands
facility: Investigational Site Number 5280001
city: Warszawa
country: Poland
facility: Investigational Site Number 6160001
city: Braga
country: Portugal
facility: Investigational Site Number 6200001
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430001
city: Barcelona
country: Spain
facility: Investigational Site Number 7240002
city: Barcelona
country: Spain
facility: Investigational Site Number 7240003
city: Zürich
country: Switzerland
facility: Investigational Site Number 7560002
city: Taipei
country: Taiwan
facility: Investigational Site Number 1580001
city: Ankara
country: Turkey
facility: Investigational Site Number 7920001
city: Istanbul
country: Turkey
facility: Investigational Site Number 7920002
city: Birmingham
country: United Kingdom
facility: Investigational Site Number 8260005
city: Cambridge
country: United Kingdom
facility: Investigational Site Number 8260002
city: London
country: United Kingdom
facility: Investigational Site Number 8260001
city: Newcastle Upon Tyne
country: United Kingdom
facility: Investigational Site Number 8260004
city: Salford
country: United Kingdom
facility: Investigational Site Number 8260003
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.