A Study to Assess the Long-term Safety and Efficacy of ATB200/AT2221 in Adult Subjects With Late-Onset Pompe Disease (LOPD)

A Phase 3 Open-label Extension Study to Assess the Long-term Safety and Efficacy of Intravenous ATB200 Co-administered With Oral AT2221 in Adult Subjects With Late-onset Pompe Disease (LOPD)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04138277

Enrollment

119

Registered

2019-10-24

Start date

2019-12-18

Completion date

2024-12-31

Last updated

2026-03-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pompe Disease (Late-onset)

Keywords

Pompe, rhGAA

Brief summary

This is a multicenter, international open-label extension study of ATB200/AT2221 in adult subjects with late-onset Pompe disease (LOPD) who completed Study ATB200-03.

Detailed description

This is an open-label extension study for subjects who completed the ATB200-03 study. The subjects will stay in this study until regulatory approval or marketing authorization and/or commercialization in the participating subject's country.

Interventions

DRUGAT2221

Participants received ATB200 co-administered with AT2221 (miglustat)

BIOLOGICALATB200

Enzyme Replacement Therapy via intravenous infusion

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1\. Subject must have completed Study ATB200-03. Note: Subjects who were forced to withdraw from Study ATB200-03 for a logistical reason not related to the efficacy or safety of cipaglucosidase alfa/miglustat (eg, hospitalization for a car accident, COVID-19 pandemic, or emergency surgery) that resulted in several consecutive missed doses may have been eligible to participate in this study upon approval by the Amicus medical monitor.

Exclusion criteria

1. Subject plans to receive gene therapy or participate in another interventional study for Pompe disease. 2. Subject, if female, is pregnant or breastfeeding. 3. Subject, whether male or female, is planning to conceive a child during the study. 4. Subject had a hypersensitivity to any of the excipients in cipaglucosidase alfa or miglustat, or had a medical condition or any other extenuating circumstance that may have, in the opinion of the investigator or medical monitor, posed an undue safety risk to the subject or may have compromised his/her ability to comply with or adversely impacted protocol requirements.

Design outcomes

Primary

Measure	Time frame	Description
Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Discontinuation of Study Drug	Entire extension study (mean = 40.5 months on treatment)	Number of subjects with TEAE, TESAE, and TEAE leading to discontinuation during this long-term extension study

Secondary

Measure	Time frame	Description
Change From Baseline in 6-Minute Walk Distance (6MWD)	baseline, Week 208	Motor function was measured using the 6-minute walk distance (meters)
Change From Baseline in Sitting % Predicted Forced Vital Capacity (FVC)	baseline, Week 208	Pulmonary function was measured by sitting % predicted forced vital capacity (FVC)
Change From Baseline in Manual Muscle Testing (MMT) Lower Extremity Score	baseline, Week 208	Strength was measured by manual muscle testing (MMT) using the Medical Research Council grading scale (0 to 5 points, with 5 indicating normal function). Change from baseline values \>0 represent improvement.
Change From Baseline in the Total Score for Patient-reported Outcomes Measurement Information System (PROMIS®) - Physical Function	baseline, Week 208	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.
Change From Baseline in the Total Score for PROMIS® - Fatigue	baseline, Week 208	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 resulting in a total score range from 6 (minimum) to 30 (maximum). A lower score represented lower fatigue symptoms.
Change From Baseline in Gait, Stairs, Gower, Chair (GSGC) Test	baseline, Week 208	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).
Change From Baseline in EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Responses	baseline, Week 208	The EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: Level 1=no problems, Level 2=slight problems, Level 3=moderate problems, Level 4=severe problems, and Level 5=extreme problems. In this categorical assessment, subjects were asked to indicate their health state by ticking the box next to the most appropriate statement in each of the 5 dimensions. Outcomes for change from baseline at Week 208 include 'no change', 'worsening' relative to baseline category, or 'improvement' relative to baseline category. Changes (worsening or improvement) are shown by magnitude of change (how many Levels) in each categorical assessment.
Change From Baseline in Overall Physical Well-being (Subject's Global Impression of Change [SGIC], Question 1)	baseline, Week 208	The Subject's Global Impression of Change overall physical well-being (question 1) is scored on a 7-point rating scale ranging from "very much worse" to "very much improved."
Change From Baseline in Physician's Global Impression of Change (PGIC) Overall Status	baseline, Week 208	The Physician's Global Impression of Change (PGIC) is designed to record the physician's assessment of the subject's status, taking into account the subject's signs and symptoms and other neuromuscular symptoms, and signs relative to their status at the Baseline Visit. The PGIC 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."
Percent Change From Baseline in Creatine Kinase (U/L)	baseline, Week 208	Percent change from baseline to Week 208 in the levels of biomarker creatine kinase (CK)
Percent Change From Baseline in Urine Hex4 (mmol/Mol Creatinine)	baseline, Week 208	Percent change from baseline to Week 208 in the levels of biomarker urine Hex4.
Proportion of Subjects With Positive Anti-drug Antibodies at Baseline and Week 208	baseline, Week 208	Immunogenicity was assessed by the number (%) of subjects with positive specific anti-cipaglucosidase antibodies at baseline and at Week 208

Countries

Argentina, Australia, Austria, Belgium, Bosnia and Herzegovina, Canada, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Netherlands, New Zealand, Poland, Slovenia, South Korea, Spain, Sweden, Taiwan, United Kingdom, United States

Participant flow

Participants by arm

Arm	Count
Treatment Continued Group Participants who received ATB200 (20 mg/kg) co-administered with AT2221 (260 mg) in the feeder study who continued on that dose in this long-term extension	81
Treatment Switched Group Participants who received alglucosidase alfa/placebo in the feeder study who were switched to ATB200 (20 mg/kg) co-administered with AT2221 (260 mg) in this long-term extension	37
Total	118

Baseline characteristics

Characteristic	Treatment Continued Group	Treatment Switched Group	Total
Age at diagnosis	40.3 years STANDARD_DEVIATION 13.82	37.2 years STANDARD_DEVIATION 15.4	39.3 years STANDARD_DEVIATION 14.35
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	12 Participants	3 Participants	15 Participants
Age, Categorical Between 18 and 65 years	69 Participants	34 Participants	103 Participants
Age, Continuous	48.9 years STANDARD_DEVIATION 13.53	46.0 years STANDARD_DEVIATION 13.47	48.0 years STANDARD_DEVIATION 13.52
Enzyme Replacement Therapy (ERT)-experienced	61 Participants	29 Participants	90 Participants
ERT-naive	20 Participants	8 Participants	28 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	5 Participants	5 Participants	10 Participants
Race (NIH/OMB) Black or African American	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) More than one race	5 Participants	1 Participants	6 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	71 Participants	30 Participants	101 Participants
Sex: Female, Male Female	48 Participants	18 Participants	66 Participants
Sex: Female, Male Male	33 Participants	19 Participants	52 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	1 / 81	0 / 37
other Total, other adverse events	80 / 81	37 / 37
serious Total, serious adverse events	17 / 81	10 / 37

Outcome results

Primary

Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Discontinuation of Study Drug

Number of subjects with TEAE, TESAE, and TEAE leading to discontinuation during this long-term extension study

Time frame: Entire extension study (mean = 40.5 months on treatment)

Population: Open-label extension (OLE) Safety Population defined as all subjects who took at least one dose of ATB200/AT2221 combination treatment in Study ATB200-07

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Treatment Continued Group	Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Discontinuation of Study Drug	Subjects with TEAEs	80 Participants
Treatment Continued Group	Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Discontinuation of Study Drug	Subjects with TESAEs	17 Participants
Treatment Continued Group	Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Discontinuation of Study Drug	Subjects with TEAEs leading to discontinuation	6 Participants
Treatment Continued Group	Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Discontinuation of Study Drug	Subjects with TEAE leading to death	1 Participants
Treatment Switched Group	Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Discontinuation of Study Drug	Subjects with TEAE leading to death	0 Participants
Treatment Switched Group	Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Discontinuation of Study Drug	Subjects with TEAEs	37 Participants
Treatment Switched Group	Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Discontinuation of Study Drug	Subjects with TEAEs leading to discontinuation	2 Participants
Treatment Switched Group	Incidence of Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Discontinuation of Study Drug	Subjects with TESAEs	10 Participants

Secondary