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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03729362




Registration number
NCT03729362
Ethics application status
Date submitted
10/10/2018
Date registered
2/11/2018

Titles & IDs
Public title
A Study Comparing ATB200/AT2221 With Alglucosidase Alfa/Placebo in Adult Subjects With Late-onset Pompe Disease
Scientific title
A Phase 3 Double-blind Randomized Study to Assess the Efficacy and Safety of Intravenous ATB200 Co-administered With Oral AT2221 in Adult Subjects With Late-onset Pompe Disease Compared With Alglucosidase Alfa/Placebo
Secondary ID [1] 0 0
ATB200-03
Universal Trial Number (UTN)
Trial acronym
PROPEL
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pompe Disease (Late-onset) 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Cipaglucosidase Alfa
Treatment: Drugs - Miglustat
Treatment: Other - Alglucosidase Alfa
Treatment: Drugs - Placebo

Experimental: Cipaglucosidase Alfa/Miglustat - Participants received cipaglucosidase alfa co-administered with miglustat every 2 weeks (Q2W).

Active comparator: Alglucosidase Alfa/Placebo - Participants received alglucosidase alfa co-administered with placebo Q2W.


Treatment: Other: Cipaglucosidase Alfa
Participants received an intravenous (IV) infusion dose over a 4-hour duration every 2 weeks (Q2W).

Treatment: Drugs: Miglustat
Participants received weight-based doses 1 hour prior to cipaglucosidase alfa infusion Q2W.

Treatment: Other: Alglucosidase Alfa
Participants received an IV infusion dose over a 4-hour duration Q2W.

Treatment: Drugs: Placebo
Miglustat matching placebo was administered orally 1 hour prior to alglucosidase alfa infusion Q2W.

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline to Week 52 in 6 Minute Walk Distance (6MWD)
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [1] 0 0
Change From Baseline to Week 52 in Sitting Forced Vital Capacity (FVC; % Predicted)
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [2] 0 0
Change From Baseline to Week 52 in the Manual Muscle Test (MMT) Score for the Lower Extremities
Timepoint [2] 0 0
Baseline, Week 52
Secondary outcome [3] 0 0
Change From Baseline to Week 26 in 6MWD
Timepoint [3] 0 0
Baseline, Week 26
Secondary outcome [4] 0 0
Change From Baseline to Week 52 in the Total Score for the Patient- Reported Outcomes Measurement Information System (PROMIS®) - Physical Function
Timepoint [4] 0 0
Baseline, Week 52
Secondary outcome [5] 0 0
Change From Baseline to Week 52 in the Total Score for the PROMIS® - Fatigue
Timepoint [5] 0 0
Baseline, Week 52
Secondary outcome [6] 0 0
Change From Baseline to Week 52 in the Total Score for the Gait, Stairs, Gowers' Maneuver, and Chair (GSGC)
Timepoint [6] 0 0
Baseline, Week 52
Secondary outcome [7] 0 0
Change From Baseline to Week 52 in Rasch-Built Pompe-Specific Activity (R-PAct) Total Score
Timepoint [7] 0 0
Baseline, Week 52
Secondary outcome [8] 0 0
Change From Baseline to Week 52 in European Quality of Life-5 Dimensions 5 Response Levels (EQ-5D-5L) Based on the EuroQol Visual Analogue Scale (EQ VAS) Quantitative Score
Timepoint [8] 0 0
Baseline, Week 52
Secondary outcome [9] 0 0
Change From Baseline to Week 52 in Sitting Slow Vital Capacity (SVC) % Predicted
Timepoint [9] 0 0
Baseline, Week 52
Secondary outcome [10] 0 0
Change From Baseline to Week 52 in Maximal Inspiratory Pressure (MIP) % Predicted
Timepoint [10] 0 0
Baseline, Week 52
Secondary outcome [11] 0 0
Change From Baseline to Week 52 in Maximal Expiratory Pressure (MEP) % Predicted
Timepoint [11] 0 0
Baseline, Week 52
Secondary outcome [12] 0 0
Change From Baseline to Week 52 in Sniff Nasal Inspiratory Pressure (SNIP) % Predicted
Timepoint [12] 0 0
Baseline, Week 52
Secondary outcome [13] 0 0
Change From Baseline to Week 52 in % Predicted 6MWD
Timepoint [13] 0 0
Baseline, Week 52
Secondary outcome [14] 0 0
Change From Baseline to Week 52 in the Quantitative Muscle Test (QMT) Values
Timepoint [14] 0 0
Baseline, Week 52
Secondary outcome [15] 0 0
Change From Baseline to Week 52 in Other MMT Scores
Timepoint [15] 0 0
Baseline, Week 52
Secondary outcome [16] 0 0
Change From Baseline to Week 52 in Maximum Vital Capacity (Maximum VC) % Predicted
Timepoint [16] 0 0
Baseline, Week 52
Secondary outcome [17] 0 0
Change From Baseline to Week 52 in PROMIS-Dyspnea and Upper Extremities Total Scores
Timepoint [17] 0 0
Baseline, Week 52
Secondary outcome [18] 0 0
Change From Baseline in the Time to Complete Individual GSGC Component Tests and Timed Up and Go (TUG) Test at Week 52
Timepoint [18] 0 0
Baseline, Week 52
Secondary outcome [19] 0 0
Physician's Global Impression of Change (PGIC) Overall Status at Week 52
Timepoint [19] 0 0
Week 52
Secondary outcome [20] 0 0
Subject's Global Impression of Change (SGIC) at Week 52
Timepoint [20] 0 0
Week 52
Secondary outcome [21] 0 0
Number of Participants Improving on Both 6MWD and % Predicted FVC at Week 52
Timepoint [21] 0 0
Week 52
Secondary outcome [22] 0 0
Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs)
Timepoint [22] 0 0
Baseline up to Week 52
Secondary outcome [23] 0 0
Change From Baseline to Week 52 in Urinary Hexose Tetrasaccharide (Hex4) Level
Timepoint [23] 0 0
Baseline, Week 52
Secondary outcome [24] 0 0
Change From Baseline to Week 52 in Serum Creatine Kinase (CK) Level
Timepoint [24] 0 0
Baseline, Week 52
Secondary outcome [25] 0 0
Population Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Experienced Participants Using Plasma Total GAA Protein Level by Signature Peptide Assay and Plasma Miglustat Concentration
Timepoint [25] 0 0
Days 1 and 364 (Week 52)
Secondary outcome [26] 0 0
Population PK: Area Under the Concentration-Time Curve (AUC) of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Experienced Participants Using Plasma Total GAA Protein Level by Signature Peptide Assay and Plasma Miglustat Concentration
Timepoint [26] 0 0
Days 1 and 364 (Week 52)
Secondary outcome [27] 0 0
Population PK: Cmax of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Participants
Timepoint [27] 0 0
Days 1 and 364 (Week 52)
Secondary outcome [28] 0 0
Population PK: AUC of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Subjects
Timepoint [28] 0 0
Days 1 and 364 (Week 52)
Secondary outcome [29] 0 0
Noncompartmental Analysis: Cmax of Plasma Total GAA Protein by Signature Peptide T09 in ERT-Naïve Subjects
Timepoint [29] 0 0
Day 1
Secondary outcome [30] 0 0
Noncompartmental Analysis: AUC From Time 0 (Predose) to the Time of Last Quantifiable Concentration of Plasma Total GAA Protein by Signature Peptide T09 in ERT-Naïve Subjects
Timepoint [30] 0 0
Day 1
Secondary outcome [31] 0 0
Comparison of Cmax of Cipaglucosidase Alfa in ERT-Experienced and ERT-Naïve Populations
Timepoint [31] 0 0
Days 1 and 364 (Week 52)
Secondary outcome [32] 0 0
Comparison of AUC of Cipaglucosidase Alfa in ERT- Experienced and ERT-Naïve Populations
Timepoint [32] 0 0
Days 1 and 364 (Week 52)

Eligibility
Key inclusion criteria
1. Subject must provide signed informed consent prior to any study-related procedures being performed.
2. Male and female subjects are = 18 years old and weigh = 40 kg at screening.
3. Female subjects of childbearing potential and male subjects must agree to use medically accepted methods of contraception during the study and for 90 days after the last dose of study drug.
4. Subject must have a diagnosis of LOPD based on documentation of one of the following:

1. deficiency of GAA enzyme
2. GAA genotyping
5. Subject is classified as one of the following with respect to ERT status:

1. ERT-experienced, defined as currently receiving standard of care ERT (alglucosidase alfa) at the recommended dose and regimen (ie, 20 mg/kg dose every 2 weeks) for = 24 months
2. ERT-naïve, defined as never having received investigational or commercially available ERT
6. Subject has a sitting FVC = 30% of the predicted value for healthy adults (National Health and Nutrition Examination Survey III) at screening.
7. Subject performs two 6MWTs at screening that are valid, as determined by the clinical evaluator, and that meet all of the following criteria:

1. both screening values of 6MWD are = 75 meters
2. both screening values of 6MWD are = 90% of the predicted value for healthy adults
3. the lower value of 6MWD is within 20% of the higher value of 6MWD
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

1. Subject has received any investigational therapy or pharmacological treatment for Pompe disease, other than alglucosidase alfa, within 30 days or 5 half-lives of the therapy or treatment, whichever is longer, before Day 1 or is anticipated to do so during the study.
2. Subject has received gene therapy for Pompe disease
3. Subject is taking any of the following prohibited medications within 30 days before Day 1:

* miglitol (eg, Glyset)
* miglustat (eg, Zavesca)
* acarbose (eg, Precose or Glucobay)
* voglibose (eg, Volix, Vocarb, or Volibo)

Note: None of these medications have a half-life that, when multiplied by 5, is longer than 30 days.
4. Subject requires the use of invasive or noninvasive ventilation support for > 6 hours per day while awake.
5. Subject has a hypersensitivity to any of the excipients in ATB200, alglucosidase alfa, or AT2221.
6. Subject has a medical condition or any other extenuating circumstance that may, in the opinion of the investigator or medical monitor, pose an undue safety risk to the subject or may compromise his/her ability to comply with or adversely impact protocol requirements. This includes clinical depression (as diagnosed by a psychiatrist or other mental health professional) with uncontrolled or poorly controlled symptoms.
7. Subject, if female, is pregnant or breastfeeding at screening.
8. Subject, whether male or female, is planning to conceive a child during the study.
9. Subject does not have documentation of diagnosis of Pompe disease and refuses to undergo genetic testing.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC
Recruitment hospital [1] 0 0
Royal Brisbane & Women's Hospital - Herston
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Monash Medical Centre - Melbourne
Recruitment hospital [4] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3168 - Melbourne
Recruitment postcode(s) [4] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Kansas
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Montana
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Utah
Country [19] 0 0
United States of America
State/province [19] 0 0
Virginia
Country [20] 0 0
Argentina
State/province [20] 0 0
Buenos Aires
Country [21] 0 0
Austria
State/province [21] 0 0
Innsbruck
Country [22] 0 0
Belgium
State/province [22] 0 0
Leuven
Country [23] 0 0
Bosnia and Herzegovina
State/province [23] 0 0
Banja Luka
Country [24] 0 0
Bulgaria
State/province [24] 0 0
Sofia
Country [25] 0 0
Canada
State/province [25] 0 0
Alberta
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario
Country [27] 0 0
Denmark
State/province [27] 0 0
Aarhus N
Country [28] 0 0
Denmark
State/province [28] 0 0
Copenhagen
Country [29] 0 0
France
State/province [29] 0 0
Bron
Country [30] 0 0
France
State/province [30] 0 0
Garches
Country [31] 0 0
France
State/province [31] 0 0
Lille
Country [32] 0 0
France
State/province [32] 0 0
Marseille
Country [33] 0 0
France
State/province [33] 0 0
Nice
Country [34] 0 0
Germany
State/province [34] 0 0
Bavaria
Country [35] 0 0
Germany
State/province [35] 0 0
NRW
Country [36] 0 0
Germany
State/province [36] 0 0
Sachsen-Anhalt
Country [37] 0 0
Greece
State/province [37] 0 0
Attica
Country [38] 0 0
Hungary
State/province [38] 0 0
Budapest
Country [39] 0 0
Hungary
State/province [39] 0 0
Pécs
Country [40] 0 0
Hungary
State/province [40] 0 0
Szeged
Country [41] 0 0
Italy
State/province [41] 0 0
NAP
Country [42] 0 0
Japan
State/province [42] 0 0
Hokkaido
Country [43] 0 0
Japan
State/province [43] 0 0
Fukuoka
Country [44] 0 0
Japan
State/province [44] 0 0
Kagoshima
Country [45] 0 0
Japan
State/province [45] 0 0
Osaka
Country [46] 0 0
Japan
State/province [46] 0 0
Tokyo
Country [47] 0 0
Korea, Republic of
State/province [47] 0 0
Gyeongsangnam-do
Country [48] 0 0
Korea, Republic of
State/province [48] 0 0
Seoul
Country [49] 0 0
Netherlands
State/province [49] 0 0
Rotterdam
Country [50] 0 0
New Zealand
State/province [50] 0 0
Auckland
Country [51] 0 0
Poland
State/province [51] 0 0
Malogoskie
Country [52] 0 0
Poland
State/province [52] 0 0
Rzeszów
Country [53] 0 0
Slovenia
State/province [53] 0 0
Ljubljana
Country [54] 0 0
Spain
State/province [54] 0 0
Barcelona
Country [55] 0 0
Sweden
State/province [55] 0 0
Gothenburg
Country [56] 0 0
Taiwan
State/province [56] 0 0
Taipei
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Birmingham
Country [58] 0 0
United Kingdom
State/province [58] 0 0
Cambridge
Country [59] 0 0
United Kingdom
State/province [59] 0 0
London
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amicus Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.