A Study Comparing ATB200/AT2221 With Alglucosidase Alfa/Placebo in Adult Subjects With Late-onset Pompe Disease (PROPEL)

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

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.

Study Overview

• Status: Completed
• Conditions: Pompe Disease (Late-onset)
• Intervention / Treatment: Biological: Cipaglucosidase Alfa; Drug: Miglustat; Biological: Alglucosidase Alfa; Drug: Placebo

Detailed Description

This is a double-blind, randomized, multicenter, international study of ATB200/AT2221 in adult subjects with late-onset Pompe disease (LOPD) who have received enzyme replacement therapy with alglucosidase alfa (ie, ERT-experienced) or who have never received ERT (ie, ERT naïve) compared with alglucosidase alfa/placebo.

The study will consist of a screening period up to 30 days, a 12-month treatment period, and a 30 day safety follow-up period. Subjects who complete this study will have the option to participate in an open label extension study to receive ATB200/AT2221 under a separate protocol.

Enzyme replacement therapy-experienced subjects will continue to take alglucosidase alfa during the screening period; treatment with alglucosidase alfa will then be replaced by study drug (ATB200/AT2221 or alglucosidase alfa/placebo) on the same schedule without interruption (ie, every 2 weeks).

Infusion visits will be scheduled every 2 weeks throughout the study; assessments (eg, clinical laboratory tests) for initial safety monitoring will be performed at these visits for the first 6 weeks of the study. Study visits that include efficacy, safety, and other assessments will be scheduled approximately every 3 months and may occur over 2 days, provided all study assessments and procedures (with the exception of pharmacokinetic [PK] sample collection) are performed before administration of study drug.

Efficacy assessments (ie, functional assessments) include evaluation of ambulatory function (6MWT), motor function tests (Gait, Stair, Gowers' maneuver, and Chair [GSGC] test and Timed Up and Go [TUG] test), muscle strength (manual muscle testing and quantitative muscle testing), and pulmonary function tests (forced vital capacity [FVC], slow vital capacity [SVC], maximal inspiratory pressure [MIP], maximal expiratory pressure [MEP], and sniff nasal inspiratory pressure [SNIP]). Patient reported outcomes (Rasch-built Pompe-specific Activity [R PAct] Scale, EuroQol 5 Dimensions 5 Levels Instrument [EQ-5D-5L], Patient-Reported Outcomes Measurement Information System [PROMIS®] instruments for physical function, fatigue, dyspnea, and upper extremity, and Subject's Global Impression of Change). The Physician's Global Impression of Change will also be performed.

Pharmacodynamic assessments include measurement of biomarkers of muscle injury (creatine kinase [CK]) and disease substrate (urinary hexose tetrasaccharide [Hex4]). Blood samples will be collected for determination of total GAA protein levels and AT2221 concentrations in plasma for a population PK analysis. Safety assessments include monitoring of adverse events (AEs), including infusion associated reactions (IARs), clinical laboratory tests (chemistry, hematology, and urinalysis), vital signs, physical examinations including weight, electrocardiograms (ECGs), and immunogenicity. Concomitant medications and nondrug therapies will also be recorded.

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, B1629ODT
    • Hospital Universitario Austral
• Australia
  • Westmead, Australia, 2145
    • Westmead Hospital
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane & Women's Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3168
      • Monash Medical Centre
• Austria
  • Innsbruck, Austria
    • Medizinische Universität Innsbruck
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • University Clinical Centre of the Republic of Srpska
• Bulgaria
  • Sofia, Bulgaria
    • UMHAT Alexandrovska
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Heritage Medical Research Clinic, University of Calgary
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical Centre
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitets Hospital
  • Copenhagen, Denmark, 2100
    • Rigshospitalet Copenhagen Neuromuscular Center
• France
  • Bron, France, 69677
    • Hôpital Neurologique Pierre Wertheimer
  • Garches, France, 92380
    • Hopital Raymond Poincare
  • Lille, France, 59037
    • Hôpital Salengro
  • Marseille, France, 13385
    • Hôpital de la Timone
  • Nice, France, 06001
    • Hôpital Pasteur
• Germany
  • Bavaria
    • Munich, Bavaria, Germany, 80336
      • Friedrich-Baur Institut
  • North Rhine-Westphalia
    • Bonn, North Rhine-Westphalia, Germany, 53105
      • Universitätsklinikum Bonn
    • Münster, North Rhine-Westphalia, Germany, 48149
      • Universitätsklinikum Münster
  • Saxony-Anhalt
    • Halle, Saxony-Anhalt, Germany, 06120
      • Universitätsklinikum Halle (Saale)
• Greece
  • Attica
    • Athens, Attica, Greece, 11528
      • Eginition Hospital
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis University, Institute of Genomic Medicine and Rare Disease
  • Pécs, Hungary, 7623
    • University of Pecs
  • Szeged, Hungary, 6725
    • University of Szeged
• Italy
  • NAP
    • Messina, NAP, Italy, 98125
      • UOC di Neurologia e Malattie Neuromuscolari
    • Napoli, NAP, Italy, 80131
      • UOC Genetica Medica
• Japan
  • Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Kagoshima, Japan
    • Kagoshima University Hospital
  • Osaka, Japan
    • Izumi City General Hospital
  • Tokyo, Japan
    • National Center of Neurology and Psychiatry
  • Tokyo, Japan, 105-8471
    • The Jikei University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060 8648
      • Hokkaido University Hospital
• Netherlands
  • Rotterdam, Netherlands, 3015GD
    • Erasmus MC
• New Zealand
  • Auckland, New Zealand
    • University of Auckland
• Poland
  • Małogoskie, Poland, 31-066
    • Szpital Uniwersytecki w Krakowie
  • Rzeszów, Poland, 35-326
    • Centrum Medyczne
• Slovenia
  • Ljubljana, Slovenia, 1000
    • University Medical Centre Ljubljana
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Gyeongsangnam-do
    • Yangsan, Gyeongsangnam-do, South Korea, 50612
      • Pusan National University
• Spain
  • Barcelona, Spain, 08026
    • Hospital De La Santa Creu I Sant Pau
• Sweden
  • Gothenburg, Sweden, 41345
    • Sahlgrenska University Hospital
• Taiwan
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
• United Kingdom
  • Birmingham, United Kingdom
    • Queen Elizabeth Hospital Birmingham
  • Cambridge, United Kingdom
    • Cambridge University Hospitals
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital NHS
  • Salford, United Kingdom, M6 8HD
    • Salford Royal NHS Foundation Trust
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85028
      • Neuromuscular Research Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Irvine, California, United States, 92868
      • University of California, Irvine
  • Florida
    • Gainesville, Florida, United States, 32610
      • UF Helath: University of Florida Clinical Research Center
    • Tampa, Florida, United States, 33612
      • University of South Florida Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Clinic
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Neuroscience Center
  • Kansas
    • Kansas City, Kansas, United States, 66205
      • University of Kansas Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Clinical Research Unit
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • Manhasset, New York, United States, 11030
      • The Feinstein Institute for Medical Research
    • New York, New York, United States, 10017
      • NYU School of Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Neurology
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah, Center for Clinical and Translational Sciences
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Lysosomal and Rare Disorders Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cipaglucosidase Alfa/Miglustat; Participants received cipaglucosidase alfa co-administered with miglustat every 2 weeks (Q2W).	Biological: Cipaglucosidase Alfa; Participants received an intravenous (IV) infusion dose over a 4-hour duration every 2 weeks (Q2W).; Other Names: ATB200; Drug: Miglustat; Participants received weight-based doses 1 hour prior to cipaglucosidase alfa infusion Q2W.; Other Names: AT2221
Active Comparator: Alglucosidase Alfa/Placebo; Participants received alglucosidase alfa co-administered with placebo Q2W.	Biological: Alglucosidase Alfa; Participants received an IV infusion dose over a 4-hour duration Q2W.; Other Names: Myozyme; Drug: Placebo; Miglustat matching placebo was administered orally 1 hour prior to alglucosidase alfa infusion Q2W.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 52 in 6 Minute Walk Distance (6MWD)	The efficacy of cipaglucosidase alfa/miglustat co-administration on ambulatory function was measured by the 6MWT. The 6MWD, measured in meters, is the distance walked on the 6MWT. A greater distance indicated greater endurance. An increase from baseline indicated improvement.	Baseline, Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 52 in Sitting Forced Vital Capacity (FVC; % Predicted)	The efficacy of cipaglucosidase alfa/miglustat co-administration on pulmonary function was measured by sitting FVC (% predicted). FVC is a standard pulmonary function test used to quantify respiratory muscle weakness.	Baseline, Week 52
Change From Baseline to Week 52 in the Manual Muscle Test (MMT) Score for the Lower Extremities	The total score for the MMT lower extremity strength included the following 8 body parts: right/left hip flexion, right/left hip abduction, right/left knee flexion and right/left knee extension. The MMT lower extremity score ranged from 0 to 40, with lower scores indicating weaker muscle strength. An increase from baseline indicated increased muscle strength.	Baseline, Week 52
Change From Baseline to Week 26 in 6MWD	The 6MWD, measured in meters, is the distance walked on the 6MWT.	Baseline, Week 26
Change From Baseline to Week 52 in the Total Score for the Patient- Reported Outcomes Measurement Information System (PROMIS®) - Physical Function	Physical Function Short Form 20a (v2.0) consisted of 20 questions. The first 14 questions were each scored on a scale from 1 to 5 as follows: 1 = unable to do; 2 = with much difficulty; 3 = with some difficulty; 4 = with a little difficulty; 5 = without any difficulty; the next 6 questions were each scored on a scale from 1 to 5 as follows: 1 = cannot do; 2 = quite a lot; 3 = somewhat; 4 = very little; 5 = not at all. The total score was calculated by summing up scores (1 to 5) across all items. Total scores range from 20 to 100. A higher score represented a better outcome.	Baseline, Week 52
Change From Baseline to Week 52 in the Total Score for the PROMIS® - Fatigue	Fatigue Short Form 8a consisted of 6 questions, each scored on a scale from 1 to 5 as follows: 1 = not at all; 2 = a little bit; 3 = somewhat; 4 = quite a bit; 5 = very much; and 2 questions, each scored on a scale from 1 to 5 as follows: 1 = never; 2 = rarely; 3 = sometimes; 4 = often; 5 = always. The total score was calculated by summing up scores (1 to 5) across all items. A lower score represented lower fatigue symptoms.	Baseline, Week 52
Change From Baseline to Week 52 in the Total Score for the Gait, Stairs, Gowers' Maneuver, and Chair (GSGC)	The GSGC consisted of a 10-meter walk for evaluation of gait, a 4-stair climb, Gowers' maneuver, and arising from a chair. Results of the GSGC included 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 Gowers' maneuver, and 1 to 6 points for arising from a chair), and a total score. GSGC total score was the sum of the component scores from the 4 functional tests. The total score ranged from a minimum of 4 points (normal performance) to a maximum of 27 points (worst performance).	Baseline, Week 52
Change From Baseline to Week 52 in Rasch-Built Pompe-Specific Activity (R-PAct) Total Score	The R-PAct scale was an 18-item questionnaire to measure limitations in activities and restriction in social participation. Possible responses to questions were as follows: unable to perform, able to perform, but with difficulty, and able to perform without difficulty. The total score was calculated by summing up the observed scores across the 18 items and it ranged from 0 to 36, with higher values representing lower level of disease impact on the muscles.	Baseline, Week 52
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	The EuroQol Visual Analogue Scale (EQ VAS) is a vertical visual analogue scale that records the respondent's own assessment of his or her overall health status at the time of completion. Scores range from 0 (the worst health you can imagine) to 100 (the best health you can imagine). Higher EQ VAS scores represent an improved sense of overall health while lower scores represent a worsening of overall health.	Baseline, Week 52
Change From Baseline to Week 52 in Sitting Slow Vital Capacity (SVC) % Predicted	SVC is a standard pulmonary function test used to quantify respiratory muscle weakness.	Baseline, Week 52
Change From Baseline to Week 52 in Maximal Inspiratory Pressure (MIP) % Predicted	The percent predicted values of MIP were calculated as: % predicted = (actual result / predicted result)* 100, where the predicted results were obtained using the reference equations from Uldry and Fitting (1995).	Baseline, Week 52
Change From Baseline to Week 52 in Maximal Expiratory Pressure (MEP) % Predicted	The percent predicted values of MEP were calculated as: % predicted = (actual result / predicted result) * 100, where the predicted results were obtained using the reference equations from Uldry and Fitting (1995).	Baseline, Week 52
Change From Baseline to Week 52 in Sniff Nasal Inspiratory Pressure (SNIP) % Predicted	The percent predicted values of SNIP were calculated as: % predicted = (actual result / predicted result) * 100, where the predicted results were obtained using the reference equations from Evans and Whitelaw (2009).	Baseline, Week 52
Change From Baseline to Week 52 in % Predicted 6MWD	The % predicted 6MWD = (actual 6MWD / predicted 6MWD) * 100. The predicted values were calculated using Enright And Sherrill 1998 Reference Equations.	Baseline, Week 52
Change From Baseline to Week 52 in the Quantitative Muscle Test (QMT) Values	QMT was measured using the hand-held dynamometer. Larger values (in kg) indicated greater muscle strength.	Baseline, Week 52
Change From Baseline to Week 52 in Other MMT Scores	Each manual muscle test was evaluated on a scoring scale from 0 to 5, as follows: 0 = no muscle movement; 1 = visible muscle movement, but no movement at the joint; 2 = movement at the joint, but not against gravity; 3 = movement against gravity, but not against added resistance; 4 = movement against resistance, but less than normal; 5 = normal strength. Upper extremity score was the sum of scores for right/left shoulder abduction, right/left shoulder adduction, right/left elbow extension, and right/left elbow flexion, with the total score ranging from 0 to 40. Proximal muscle group score, the sum of scores for right/left hip flexion, right/left hip abduction, right/left shoulder abduction, and right/left shoulder adduction, with the total score ranging from 0 to 40. MMT total score was the sum of the lower and upper extremity scores and ranged from 0 to 80. Lower scores indicated lower overall muscle strength. An increase from baseline indicated improvement in muscle strength.	Baseline, Week 52
Change From Baseline to Week 52 in Maximum Vital Capacity (Maximum VC) % Predicted	Maximum VC is the greater of the two VC values (FVC or SVC).	Baseline, Week 52
Change From Baseline to Week 52 in PROMIS-Dyspnea and Upper Extremities Total Scores	The Upper Extremities Short Form 7a consisted of 7 items each scored on a decreasing scale from 1 to 5 as follows: 1 = unable to do; 2 = with much difficulty; 3 = with some difficulty; 4 = with a little difficulty; 5 = without any difficulty. Dyspnea Severity Short Form 10a consisted of 10 items each scored on a scale from 0 to 3 as follows: 0 = no shortness of breath; 1 = mildly short of breath; 2 = moderately short of breath; 3 = severely short of breath. A total score was generated for each instrument by adding up each item. Total scores for upper extremities range from 7 to 35. Total scores for dyspnea range from 0 to 30. A higher score for upper extremities represented improvement in symptoms. A lower score for dyspnea severity represented improvement in symptoms.	Baseline, Week 52
Change From Baseline in the Time to Complete Individual GSGC Component Tests and Timed Up and Go (TUG) Test at Week 52	Motor function test assessed the time to complete individual GSGC component tests (10-meter walk, 4- stair climb, Gowers' maneuver, and arise from a chair) and the TUG test. The TUG test assessed the time a subject needed to rise from a chair, walk 3 meters, turn around, walk back to the chair, and sit down.	Baseline, Week 52
Physician's Global Impression of Change (PGIC) Overall Status at Week 52	Physician's Global Impression of Change is based on a single item that is scored on a 7-point rating scale ranging from 1 "very much worse" to 7 "very much improved". A tertiary response variable (improving, declining, stable) was defined as follows: "Improving", which consisted of improved, moderately improved, and very much improved; "Declining", which consisted of worse, moderately worse, and very much worse; and "Stable", which equaled to no change.	Week 52
Subject's Global Impression of Change (SGIC) at Week 52	The SGIC is designed to record the participants' impression of their functional status since starting study drug using a 7-point scale ranging from 1 "very much worse" to 7 "very much improved". A tertiary response variable (improving, declining, stable) was defined as follows: "Improving", which consisted of improved, moderately improved, and very much improved; "Declining", which consisted of worse, moderately worse, and very much worse; and "Stable", which equaled to no change.	Week 52
Number of Participants Improving on Both 6MWD and % Predicted FVC at Week 52	A composite subject-level response of the 2 relevant clinical outcomes, 6MWD and FVC (% predicted), was assessed. Prespecified thresholds were used for assessment of improvement consistent with published minimal clinically important difference values for comparable instruments in similar disease.	Week 52
Number of Participants With Treatment-Emergent Anti-Drug Antibodies (ADAs)	Treatment-emergent ADAs were defined as participants who had seroconverted or boosted their preexisting ADA during the study period.	Baseline up to Week 52
Change From Baseline to Week 52 in Urinary Hexose Tetrasaccharide (Hex4) Level	Levels of urinary Hex4, a biomarker of disease substrate, were measured. The assay specifically targets Hex4, the glucose tetrasaccharide (Glc4), which is a biomarker of glycogen storage.	Baseline, Week 52
Change From Baseline to Week 52 in Serum Creatine Kinase (CK) Level	Change from baseline to Week 52 in serum CK level. CK levels were measured as part of the serum chemistry panel.	Baseline, Week 52
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	On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-experienced participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.	Days 1 and 364 (Week 52)
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	On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-experienced participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.	Days 1 and 364 (Week 52)
Population PK: Cmax of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Participants	On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-naïve participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.	Days 1 and 364 (Week 52)
Population PK: AUC of Cipaglucosidase Alfa and Alglucosidase Alfa in ERT-Naïve Subjects	On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis in ERT-naïve participants at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.	Days 1 and 364 (Week 52)
Noncompartmental Analysis: Cmax of Plasma Total GAA Protein by Signature Peptide T09 in ERT-Naïve Subjects	A noncompartmental analysis was performed on ERT-naïve subjects, who underwent serial PK sampling during the study. On Day 1, serial blood samples were collected for ERT-naïve participants just prior to initiation of cipaglucosidase alfa/alglucosidase alfa infusion (time 0) and at 1, 2, 3, 3.5, 4, 4.5, 6, 8, 10, and 24 hours after the start of cipaglucosidase alfa/alglucosidase alfa infusion for plasma total human acid α-glucosidase (GAA) protein signature peptide T09 and plasma miglustat determinations.	Day 1
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	A noncompartmental analysis was performed on ERT-naïve subjects, who underwent serial PK sampling during the study. On Day 1, serial blood samples were collected for ERT-naïve participants just prior to initiation of cipaglucosidase alfa/alglucosidase alfa infusion (time 0) and at 1, 2, 3, 3.5, 4, 4.5, 6, 8, 10, and 24 hours after the start of cipaglucosidase alfa/alglucosidase alfa infusion for plasma total GAA protein signature peptide T09 and plasma miglustat determinations.	Day 1
Comparison of Cmax of Cipaglucosidase Alfa in ERT-Experienced and ERT-Naïve Populations	On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.	Days 1 and 364 (Week 52)
Comparison of AUC of Cipaglucosidase Alfa in ERT- Experienced and ERT-Naïve Populations	On Days 1 and 364 (Week 52), sparse blood samples were collected for PK analysis at 0, 1, 4, 6, 12, and 24 hours post-dose. Collection of the 12-hour sample was optional.	Days 1 and 364 (Week 52)

Collaborators and Investigators

• Sponsor: Amicus Therapeutics

Publications and helpful links

General Publications

• Schoser B, Roberts M, Byrne BJ, Sitaraman S, Jiang H, Laforet P, Toscano A, Castelli J, Diaz-Manera J, Goldman M, van der Ploeg AT, Bratkovic D, Kuchipudi S, Mozaffar T, Kishnani PS; PROPEL Study Group. Safety and efficacy of cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo in late-onset Pompe disease (PROPEL): an international, randomised, double-blind, parallel-group, phase 3 trial. Lancet Neurol. 2021 Dec;20(12):1027-1037. doi: 10.1016/S1474-4422(21)00331-8.
• Kushlaf H, Diaz-Manera J, Bratkovic D, Byrne BJ, Claeys KG, Clemens PR, Dimachkie MM, Kishnani PS, Laforet P, Roberts M, Schoser B, Toscano A, Castelli J, Holdbrook F, Sitaraman Das S, Goldman M, Mozaffar T; PROPEL Study Group. Switching Enzyme Replacement Therapy for Late-Onset Pompe Disease From Alglucosidase Alfa to Cipaglucosidase Alfa Plus Miglustat: Post Hoc Effect Size Analysis of PROPEL. Muscle Nerve. 2025 Aug;72(2):230-239. doi: 10.1002/mus.28420. Epub 2025 May 7.
• Kishnani PS, Byrne BJ, Claeys KG, Diaz-Manera J, Dimachkie MM, Kushlaf H, Mozaffar T, Roberts M, Schoser B, Hummel N, Kopiec A, Holdbrook F, Shohet S, Toscano A; PROPEL Study Group. Switching treatment to cipaglucosidase alfa plus miglustat positively affects patient-reported outcome measures in patients with late-onset Pompe disease. J Patient Rep Outcomes. 2024 Nov 13;8(1):132. doi: 10.1186/s41687-024-00805-w.
• MacCulloch A, Griffiths A, Johnson N, Shohet S. Health-Related Quality-of-Life Utility Values in Adults With Late-Onset Pompe Disease: Analyses of EQ-5D Data From the PROPEL Clinical Trial. J Health Econ Outcomes Res. 2024 Sep 18;11(2):80-85. doi: 10.36469/001c.121928. eCollection 2024.
• Kishnani PS, Shohet S, Raza S, Hummel N, Castelli JP, Sitaraman Das S, Jiang H, Kopiec A, Keyzor I, Hahn A. Validation of the Patient-Reported Outcomes Measurement Information System (PROMIS(R)) physical function questionnaire in late-onset Pompe disease using PROPEL phase 3 data. J Patient Rep Outcomes. 2024 Jan 31;8(1):13. doi: 10.1186/s41687-024-00686-z.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2018
• Primary Completion (Actual): December 15, 2020
• Study Completion (Actual): January 15, 2021

Study Registration Dates

• First Submitted: October 10, 2018
• First Submitted That Met QC Criteria: November 1, 2018
• First Posted (Actual): November 2, 2018

Study Record Updates

• Last Update Posted (Estimated): September 11, 2025
• Last Update Submitted That Met QC Criteria: September 9, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Pompe; rhGAA
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lysosomal Storage Diseases, Nervous System; Glycogen Storage Disease; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Glycogen Storage Disease Type II; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs; miglustat; GAA protein, human
• Other Study ID Numbers: ATB200-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No