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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03729362
Ethics application status
Date submitted
10/10/2018
Date registered
2/11/2018
Date last updated
31/07/2019

Titles & IDs
Public title
PROPEL Study - A Study Comparing ATB200/AT2221 With Alglucosidase/Placebo in Adult Subjects With LOPD
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
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: Drugs - AT2221
Other interventions - alglucosidase alfa
Other interventions - ATB200

Experimental: ATB200/AT2221 - Participants received ATB200 co-administered with AT2221 capsule (Miglustat)

Active Comparator: alglucosidase alfa/placebo - Participants received alglucosidase alfa co-administered with placebo capsules.


Treatment: Drugs: AT2221
Participants received ATB200 co-administered with AT2221 (Miglustat)

Other interventions: alglucosidase alfa
alglucosidase alfa via intravenous infusion as prescribed by the participant's treating physician and in accordance with the approved prescribing information via intravenous infusion as prescribed by the participant's treating physician and in accordance with the approved prescribing information

Other interventions: ATB200
Enzyme Replacement Therapy via intravenous infusion

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

Outcomes
Primary outcome [1] 0 0
6-Minute Walk Test - Change in 6MWD from baseline to assess the efficacy of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo
Timepoint [1] 0 0
12 months
Secondary outcome [1] 0 0
Pulmonary Function - Forced vital capacity (FVC) - Change from baseline in FVC (sitting and supine) to assess the efficacy of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo
Timepoint [1] 0 0
12 months
Secondary outcome [2] 0 0
Manual Muscle Strength - Change in manual muscle strength from baseline to assess the efficacy of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo
Timepoint [2] 0 0
12 months
Secondary outcome [3] 0 0
Quantitative Muscle Strength - Change in Quantitative muscle strength from baseline to assess the efficacy of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo
Timepoint [3] 0 0
12 months
Secondary outcome [4] 0 0
PROMIS instruments questionnaires - Change from baseline in scores of PROMIS instruments for physical function, fatigue, dyspnea, and upper extremity questionnaire to assess the efficacy of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo. The PROMIS instruments for physical function (20 items), d upper extremity (7 items) measure signs and symptoms using general questions without a temporal reference. The PROMIS instruments for fatigue (8 items) and dyspnea severity (10 items) measure signs and symptoms over the past 7 days. A 5-point scale is used for each instrument (though responses may vary within or among instruments), and a total score is generated for each instrument.
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Motor Function - Gait, Stairs, Gower, Chair (GSGC) test - Change from baseline in GSGC score to assess the efficacy of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo. The GSGC consists of a 10-meter walk for evaluation of gait, a 4-stair climb, Gower's maneuver, and arising from a chair. Results of the GSGC include the time required to complete the individual tests, individual scores for each of the tests (1 to 7 points for each of gait, 4-stair climb, and Gower's maneuver and 1 to 6 points for arising from a chair), and a total score. The total score ranges from a minimum of 4 points (normal performance) to a maximum of 27 points (worst score).
Timepoint [5] 0 0
12 months
Secondary outcome [6] 0 0
Motor Function - Timed Up and Go (TUG) - Change from baseline in TUG to assess the efficacy of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo. The TUG test measures the time it takes for the subject to rise from a chair, walk 3 meters, turn around, walk back to the chair, and sit down will be recorded.
Timepoint [6] 0 0
12 months
Secondary outcome [7] 0 0
The Rasch-built Pompe-specific activity (R-PAct) questionnaires - Change from baseline in scores of R-PAct scale questionnaire to assess the efficacy of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo. The R-PAct scale is an 18-item questionnaire to measure limitations in activities and restriction in social participation. Possible responses to questions are as follows: unable to perform, able to perform, but with difficulty, and able to perform without difficulty. A raw score ranging from 0 to 36 points is generated. The low score indicates the highest level of disability.
Timepoint [7] 0 0
12 months
Secondary outcome [8] 0 0
EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) questionnaires - Change from baseline in scores of EQ-5D-5L questionnaire to assess the efficacy of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo. The EQ-5D-5L comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. Subjects are asked to indicate their health state by ticking the box next to the most appropriate statement in each of the 5 dimensions. The subject's self rated health is also recorded on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'.
Timepoint [8] 0 0
12 months
Secondary outcome [9] 0 0
Subject's Global Impression of Change questionnaires - Change from baseline in scores of Subject's Global Impression of Change (SGIC) questionnaire to assess the efficacy of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo. The Subject's Global Impression of Change is designed to record the subjects' impression of their functional status since starting study drug using a 7-point scale ranging from "very much worse" to "very much improved".
Timepoint [9] 0 0
12 months
Secondary outcome [10] 0 0
Physician Overall Clinical Impression - Change in the Physician's Global Impression of Change (PGIC) evaluation to assess the efficacy of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo
Timepoint [10] 0 0
12 months
Secondary outcome [11] 0 0
Pulmonary Function - Slow Vital Capacity (SVC) - Change from baseline in SVC (sitting and supine) to assess the efficacy of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo
Timepoint [11] 0 0
12 months
Secondary outcome [12] 0 0
Pulmonary Function - Maximum Inspiratory Pressure (MIP) - Change from baseline in MIP to assess the efficacy of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo
Timepoint [12] 0 0
12 months
Secondary outcome [13] 0 0
Pulmonary Function - Maximum Expiratory Pressure - Change from baseline in MEP to assess the efficacy of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo
Timepoint [13] 0 0
12 months
Secondary outcome [14] 0 0
Pulmonary Function - Sniff Nasal Inspiratory Pressure (SNIP) - Change from baseline in SNIP to assess the efficacy of ATB200/AT2221 co-administration compared with alglucosidase alfa/placebo
Timepoint [14] 0 0
12 months
Secondary outcome [15] 0 0
Number of participants with TEAEs and SARs - Evaluation of Treatment Emergent Adverse Events (TEAEs) begins after written informed consent is provided, including study related events that occur as a direct result of a study procedure to assess the safety, tolerability of ATB200/AT2221 co administration compared with alglucosidase alfa/placebo
Timepoint [15] 0 0
12 months
Secondary outcome [16] 0 0
Immunogenicity - Measurement of anti-rhGAA Abs (total, cross-reactive, and neutralizing) to assess the Immunogenicity of ATB200/AT2221 co administration compared with alglucosidase alfa/placebo
Timepoint [16] 0 0
12 months
Secondary outcome [17] 0 0
Biomarkers/Pharmacodynamics of muscle injury and disease substrate - Change from baseline in Creatine Kinase and Urinary Hexose Tetrasaccharide
Timepoint [17] 0 0
12 months
Secondary outcome [18] 0 0
popPK: Cmax - Maximum observed plasma concentration
Timepoint [18] 0 0
12 months
Secondary outcome [19] 0 0
popPK: Tmax - time to reach Tmax
Timepoint [19] 0 0
12 months
Secondary outcome [20] 0 0
popPK: AUC0-inf - Area under the curve from time 0 extrapolated to infinite time
Timepoint [20] 0 0
12 months
Secondary outcome [21] 0 0
popPK: t1/2 - terminal elimination half-live
Timepoint [21] 0 0
12 months
Secondary outcome [22] 0 0
popPK: CLT - Total Body Clearance
Timepoint [22] 0 0
12 months

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
Gender
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
Recruiting
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
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
Montana
Country [8] 0 0
United States of America
State/province [8] 0 0
New Jersey
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
Utah
Country [15] 0 0
United States of America
State/province [15] 0 0
Virginia
Country [16] 0 0
Argentina
State/province [16] 0 0
Buenos Aires
Country [17] 0 0
Belgium
State/province [17] 0 0
Leuven
Country [18] 0 0
Bosnia and Herzegovina
State/province [18] 0 0
Banja Luka
Country [19] 0 0
Bulgaria
State/province [19] 0 0
Sofia
Country [20] 0 0
Canada
State/province [20] 0 0
Alberta
Country [21] 0 0
Denmark
State/province [21] 0 0
Aarhus N
Country [22] 0 0
Denmark
State/province [22] 0 0
Copenhagen
Country [23] 0 0
France
State/province [23] 0 0
Bron
Country [24] 0 0
France
State/province [24] 0 0
Nice
Country [25] 0 0
Hungary
State/province [25] 0 0
Budapest
Country [26] 0 0
Hungary
State/province [26] 0 0
Pécs
Country [27] 0 0
Hungary
State/province [27] 0 0
Szeged
Country [28] 0 0
Korea, Republic of
State/province [28] 0 0
Seoul
Country [29] 0 0
Poland
State/province [29] 0 0
Malogoskie
Country [30] 0 0
Poland
State/province [30] 0 0
Rzeszów
Country [31] 0 0
Spain
State/province [31] 0 0
Barcelona
Country [32] 0 0
Taiwan
State/province [32] 0 0
Taipei
Country [33] 0 0
United Kingdom
State/province [33] 0 0
London
Country [34] 0 0
United Kingdom
State/province [34] 0 0
Salford

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a phase 3 double-blind randomized study to study 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.
Trial website
https://clinicaltrials.gov/show/NCT03729362
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
For Site
Address 0 0
Country 0 0
Phone 0 0
609-662-2000
Fax 0 0
Email 0 0
PompeSiteInfo@amicusrx.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03729362