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

Amicus Therapeutics119 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

119

Conditions

Pompe Disease (Late-onset)

Interventions

AT2221DRUG

Participants received ATB200 co-administered with AT2221 (miglustat)

ATB200BIOLOGICAL

Enzyme Replacement Therapy via intravenous infusion

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (60)

Outcomes

Primary Outcomes

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)

Secondary Outcomes

Change From Baseline in 6-Minute Walk Distance (6MWD)

Motor function was measured using the 6-minute walk distance (meters)

Time frame: baseline, Week 208

Change From Baseline in Sitting % Predicted Forced Vital Capacity (FVC)

Pulmonary function was measured by sitting % predicted forced vital capacity (FVC)

Time frame: baseline, Week 208

Change From Baseline in Manual Muscle Testing (MMT) Lower Extremity Score

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.

Time frame: baseline, Week 208

Change From Baseline in the Total Score for 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.

Time frame: baseline, Week 208

Data from ClinicalTrials.gov

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University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

University of California, Irvine

Irvine, California, United States

University of Florida Clinical Research Center

Gainesville, Florida, United States

Emory Clinic

Atlanta, Georgia, United States

IU Health Neuroscience Center

Indianapolis, Indiana, United States

Washington University School of Medicine

St Louis, Missouri, United States

Billings Clinic

Billings, Montana, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Northwell Health

Great Neck, New York, United States

NYU School of Medicine

New York, New York, United States

...and 50 more locations

Change From Baseline in the Total Score for 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 resulting in a total score range from 6 (minimum) to 30 (maximum). A lower score represented lower fatigue symptoms.

Time frame: baseline, Week 208

Change From Baseline in Gait, Stairs, Gower, Chair (GSGC) Test

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).

Time frame: baseline, Week 208

Change From Baseline in EuroQol 5 Dimensions 5 Levels (EQ-5D-5L) Responses

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.

Time frame: baseline, Week 208

Change From Baseline in Overall Physical Well-being (Subject's Global Impression of Change [SGIC], Question 1)

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."

Time frame: baseline, Week 208

Change From Baseline in Physician's Global Impression of Change (PGIC) Overall Status

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."

Time frame: baseline, Week 208

Percent Change From Baseline in Creatine Kinase (U/L)

Percent change from baseline to Week 208 in the levels of biomarker creatine kinase (CK)

Time frame: baseline, Week 208

Percent Change From Baseline in Urine Hex4 (mmol/Mol Creatinine)

Percent change from baseline to Week 208 in the levels of biomarker urine Hex4.

Time frame: baseline, Week 208

Proportion of Subjects With Positive Anti-drug Antibodies at Baseline and Week 208

Immunogenicity was assessed by the number (%) of subjects with positive specific anti-cipaglucosidase antibodies at baseline and at Week 208

Time frame: baseline, Week 208