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Trial record 2 of 3 for:    COMET pompe

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 (COMET)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02782741
Recruitment Status : Active, not recruiting
First Posted : May 25, 2016
Results First Posted : April 8, 2021
Last Update Posted : May 27, 2022
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Genzyme, a Sanofi Company )

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).


Condition or disease Intervention/treatment Phase
Glycogen Storage Disease Type II;Pompe's Disease Drug: Avalglucosidase alfa (GZ402666) Drug: Alglucosidase alfa (GZ419829) Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : November 2, 2016
Actual Primary Completion Date : March 19, 2020
Estimated Study Completion Date : May 2023


Arm Intervention/treatment
Experimental: avalglucosidase alfa (GZ402666)
Administered intravenously every 2 weeks
Drug: Avalglucosidase alfa (GZ402666)
Pharmaceutical form: powder for concentrate for solution for infusion Route of administration: intravenous

Active Comparator: alglucosidase alfa (GZ419829)
Administered intravenously every 2 weeks
Drug: Alglucosidase alfa (GZ419829)
Pharmaceutical form: powder for concentrate for solution for infusion Route of administration: intravenous
Other Names:
  • Myozyme
  • Lumizyme




Primary Outcome Measures :
  1. PAP: Change From Baseline in Percent Predicted Forced Vital Capacity in Upright Position at Week 49 [ Time Frame: Baseline, 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 (% 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.


Secondary Outcome Measures :
  1. PAP: Change From Baseline in Total Distance Walked During Six-minute Walk Test (6MWT) at Week 49 [ Time Frame: Baseline, Week 49 ]
    6MWT was a standardized test that measured the distance (in meters) covered by the participant by walking on a flat, hard surface in a period of a 6-minute walk. Mean distance walked gives an indication of functional endurance. The greater the distance (that a participant could walk in 6 minutes), the greater the endurance. LS mean and SE were derived from MMRM model with baseline FVC (% predicted) and baseline 6MWT (distance walked in meter), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

  2. PAP: Change From Baseline in Percent Predicted Maximal Inspiratory Pressure (MIP) in Upright Position at Week 49 [ Time Frame: Baseline, Week 49 ]
    MIP is a quick and non-invasive test to measure strength of inspiratory muscles, primarily diaphragm, and allows for assessment of ventilatory failure, restrictive lung disease and respiratory muscle strength. MIP refers to how much air pressure force an individual creates by inhaling through the mouth as hard as possible. LS mean and SE were derived from MMRM model for MIP % predicted adjusted for MIP % predicted at baseline, age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

  3. PAP: Change From Baseline in Percent Predicted Maximal Expiratory Pressure (MEP) in Upright Position at Week 49 [ Time Frame: Baseline, Week 49 ]
    MEP is a quick and non-invasive test to measure strength of expiratory muscles, primarily diaphragm, and allows for assessment of ventilatory failure, restrictive lung disease and respiratory muscle strength. MEP is the greater pressure generated during maximal expiration. LS mean and SE were derived from MMRM model for MEP % predicted adjusted for MEP % predicted at baseline, age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

  4. PAP: Change From Baseline in Lower Extremity Muscle Strength at Week 49 as Assessed by Hand-held Dynamometry (HHD) [ Time Frame: Baseline, Week 49 ]
    HHD: a portable method for strength quantitation. To complete a make test, participant exerted maximal force against dynamometer with gradual increase in force and completed isometric hold for 4-5 seconds. Muscle strengths were collected in Newton. Every muscle group (hip: flexion, extension, abduction; knee: flexion, extension and ankle dorsiflexion) were measured 2 times and highest value was reported. Summary score was sum of 12 measurements (2 measurements per muscle group) from 6 muscle groups on each side (left and right). An increase from Baseline was reflective of increased muscle strength, whereas a decrease from Baseline was reflective of decreased muscle strength. LS mean and SE were derived from MMRM model for HHD lower extremity muscle strength composite score adjusted for summary HHD lower extremity score at baseline, baseline FVC (% predicted), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

  5. PAP: Change From Baseline in Quick Motor Function Test (QMFT) Total Scores at Week 49 [ Time Frame: Baseline, Week 49 ]
    The QMFT was an observer administered test to evaluate changes in motor function. QMFT comprised of 16 items specifically difficult for participants with Pompe disease. Each item was scored separately on a 5-point ordinal scale (ranged from 0 to 4, higher score indicated better outcome). Total QMFT score was obtained by adding the scores of all items and ranged from 0 (unable to perform motor function tests) to 64 (normal muscle function), higher score represented better outcome. LS mean and SE were derived from MMRM models adjusted for total QMFT score at baseline, baseline FVC (% predicted), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

  6. 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 [ Time Frame: Baseline, Week 49 ]
    SF-12, a 12 item-questionnaire, used to assess health-related quality of life in participants aged >=18 years at screening/baseline. SF-12 consisted of 12 items, which were categorized into eight domains (subscales) of functioning and well-being: physical functioning, role-physical, role emotional, mental health, bodily pain, general health, vitality and social functioning, with each domain score ranged from 0 (poor health) to 100 (better health), higher scores indicated good health condition. These eight domains were further summarized into 2 summary scores, PCS and MCS. The score range for each of these 2 summary scores was from 0 (poor health) to 100 (better health), higher scores indicated a better health-related quality of life. LS mean and SE were derived from MMRM models adjusted for baseline score (PCS or MCS), baseline FVC (% predicted), age (in years, at baseline), gender, treatment group, visit, and treatment-by-visit interaction as fixed effects.

  7. PAP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Infusion-associated Reactions (IARs) [ Time Frame: From Baseline up to Week 49 ]
    AE: any untoward medical occurrence in participant who took study drug and not necessarily have to had causal relationship with treatment. TEAEs: AEs that developed/worsened in grade/became serious during TEAE period in PAP (from time of 1st treatment date to last treatment date+4 weeks for participants who didn't receive any treatment in open-label or to time just prior to 1st treatment in open-label for participants who received treatment in open-label). Protocol-defined IARs: AE of special interest (AESIs) that occurred during either infusion/observation period following infusion which were deemed to be related/possibly related to study drug. Algorithm-defined IARs: any TEAE meeting either 1 of 2 criteria: 1) event occurred from start to end of infusion + 24 hours, considered related to study drug, 2) If AE time component missed, compare AE start date with infusion start and end date. If AE start date was between infusion start and end date + 1 day and it was related to study drug.

  8. Open-label Period: Number of Participants With Treatment-emergent Adverse Events and Infusion-associated Reactions [ Time Frame: Week 50 to 145 in open-label long-term period ]
    AE: any untoward medical occurrence in a participant who received study drug and did not necessarily have to had a causal relationship with treatment. TEAEs in open-label: AEs that developed/worsened in grade/became serious during TEAE period in open-label (from time of 1st open-label treatment to last treatment date + 4 weeks). Protocol-defined IARs: defined as AESIs that occurred during either infusion/observation period following infusion which were deemed to be related/possibly related to study drug. Algorithm-defined IARs: any TEAE meeting either 1 of 2 criteria: 1) event occurred from start to end of infusion plus 24 hours, considered related to study drug, 2) If AE time component missed, compare AE start date with infusion start and end date. If AE start date was between infusion start and end date plus 1 day and it was related to study drug.

  9. PAP: Percentage of Participants With Treatment-emergent Antidrug Antibodies (ADA) Response [ Time Frame: From Baseline up to Week 49 ]
    ADA response categories: 1) Treatment-induced: ADAs developed following administration of the study drug. If the baseline ADA sample was missing or non-reportable and at least one reportable on-treatment ADA sample was available, the baseline sample was considered as "negative". 2) Treatment-boosted: Pre-existing ADAs that were boosted at least two titer steps from baseline (i.e., 4 fold increase in titers) following administration of the study drug (any time after the first drug administration). 3) Treatment emergent: combination of treatment induced and treatment boosted.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   3 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02782741


Locations
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United States, Arizona
Investigational Site Number 8400015
Phoenix, Arizona, United States, 85013
United States, California
Investigational Site Number 8400020
Los Angeles, California, United States, 90095
Investigational Site Number 8400011
Orange, California, United States, 92868
Investigational Site Number 8400017
Stanford, California, United States, 94305
United States, Florida
Investigational Site Number 8400016
Gainesville, Florida, United States, 32610
United States, Georgia
Investigational Site Number 8400007
Decatur, Georgia, United States, 30033
United States, Illinois
Investigational Site Number 8400023
Chicago, Illinois, United States, 60611
United States, Iowa
Investigational Site Number 8400002
Iowa City, Iowa, United States, 52242
United States, Kansas
Investigational Site Number 8400012
Kansas City, Kansas, United States, 66160-7321
United States, Massachusetts
Investigational Site Number 8400010
Boston, Massachusetts, United States, 02114
United States, Michigan
Investigational Site Number 8400001
Detroit, Michigan, United States, 48201
United States, Minnesota
Investigational Site Number 8400019
Minneapolis, Minnesota, United States, 55455
United States, New York
Investigational Site Number 8400026
Great Neck, New York, United States, 11020
Investigational Site Number 8400008
Valhalla, New York, United States, 10595
United States, North Carolina
Investigational Site Number 8400006
Durham, North Carolina, United States, 27710
United States, Ohio
Investigational Site Number 8400009
Cincinnati, Ohio, United States, 45267-0542
United States, Oregon
Investigational Site Number 8400014
Portland, Oregon, United States, 97239
United States, Pennsylvania
Investigational Site Number 8400025
Pittsburgh, Pennsylvania, United States, 15213
United States, Utah
Investigational Site Number 8400018
Salt Lake City, Utah, United States, 84132
United States, Virginia
Investigational Site Number 8400005
Fairfax, Virginia, United States, 22030
United States, West Virginia
Investigational Site Number 8400024
Morgantown, West Virginia, United States, 26506
Argentina
Investigational Site Number 0320001
Caba, Argentina, C1181ACH
Australia
Investigational Site Number 0360001
Auchenflower, Australia, 4066
Austria
Investigational Site Number 0400001
Wien, Austria, 1090
Belgium
Investigational Site Number 0560003
Bruxelles, Belgium, 1070
Investigational Site Number 0560001
Leuven, Belgium, 3000
Brazil
Investigational Site Number 0760004
Brasilia, Brazil, 71625-009
Investigational Site Number 0760001
Sao Paulo, Brazil, 04037-002
Canada
Investigational Site Number 1240003
Hamilton, Canada, L8N 3Z5
Investigational Site Number 1240002
Montreal, Canada, H3A 2B4
Czechia
Investigational Site Number 2030001
Praha 2, Czechia, 12808
Denmark
Investigational Site Number 2080003
København Ø, Denmark, 2100
France
Investigational Site Number 2500008
Angers, France, 49933
Investigational Site Number 2500007
Bordeaux, France
Investigational Site Number 2500011
Brest Cedex 2, France, 29609
Investigational Site Number 2500004
Bron, France, 69677
Investigational Site Number 2500010
Clermont Ferrand, France, 63003
Investigational Site Number 2500005
Lille, France, 59037
Investigational Site Number 2500006
Marseille Cedex 5, France, 13385
Investigational Site Number 2500001
Paris, France, 75013
Germany
Investigational Site Number 2760006
Bochum, Germany, 44789
Investigational Site Number 2760001
Mainz, Germany, 55131
Investigational Site Number 2760003
München, Germany, 80336
Investigational Site Number 2760002
Münster, Germany, 48149
Hungary
Investigational Site Number 3480001
Budapest, Hungary, 1083
Italy
Investigational Site Number 3800006
Brescia, Italy, 25123
Investigational Site Number 3800001
Messina, Italy, 98125
Investigational Site Number 3800002
Milano, Italy, 20122
Investigational Site Number 3800007
Napoli, Italy, 80131
Investigational Site Number 3800003
Torino, Italy, 10126
Japan
Investigational Site Number 3920002
Kodaira-Shi, Japan
Korea, Republic of
Investigational Site Number 4100001
Seoul, Korea, Republic of, 03080
Investigational Site Number 4100002
Seoul, Korea, Republic of, 06273
Mexico
Investigational Site Number 4840001
Mexico, Mexico
Netherlands
Investigational Site Number 5280001
Rotterdam, Netherlands, 3015 GE
Poland
Investigational Site Number 6160001
Warszawa, Poland, 02-097
Portugal
Investigational Site Number 6200001
Braga, Portugal, 4710-243
Russian Federation
Investigational Site Number 6430001
Moscow, Russian Federation, 125367
Spain
Investigational Site Number 7240002
Barcelona, Spain, 08025
Investigational Site Number 7240003
Barcelona, Spain, 08950
Switzerland
Investigational Site Number 7560002
Zürich, Switzerland, 8091
Taiwan
Investigational Site Number 1580001
Taipei, Taiwan, 10043
Turkey
Investigational Site Number 7920001
Ankara, Turkey, 06100
Investigational Site Number 7920002
Istanbul, Turkey, 34390
United Kingdom
Investigational Site Number 8260005
Birmingham, United Kingdom, B15 2GW
Investigational Site Number 8260002
Cambridge, United Kingdom, CB2 OQQ
Investigational Site Number 8260001
London, United Kingdom, NW3 2QG
Investigational Site Number 8260004
Newcastle Upon Tyne, United Kingdom, NE1 4LP
Investigational Site Number 8260003
Salford, United Kingdom, M6 8HD
Sponsors and Collaborators
Genzyme, a Sanofi Company
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi ( Genzyme, a Sanofi Company ):
Study Protocol  [PDF] December 21, 2020
Statistical Analysis Plan  [PDF] April 14, 2020

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier: NCT02782741    
Other Study ID Numbers: EFC14028
2016-000942-77 ( EudraCT Number )
U1111-1178-4806 ( Other Identifier: WHO universal trial number )
First Posted: May 25, 2016    Key Record Dates
Results First Posted: April 8, 2021
Last Update Posted: May 27, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Glycogen Storage Disease Type II
Glycogen Storage Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Carbohydrate Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases