A Study About Antibody Levels and Biomarkers in the Blood in People With Late-onset Pompe Disease

A Study to Evaluate Seroprevalence of Antibodies to AAV8 and Assessment of Biomarkers in Patients With Late-Onset Pompe Disease

Pompe disease is a genetic condition which causes muscle weakness over time. People with Pompe disease have a faulty gene that makes an enzyme called acid alpha-glucosidase (or GAA). This enzyme breaks down a type of sugar called glycogen. Without this enzyme, there is a build-up of glycogen in the cells of the body. This causes muscle weakness and other symptoms. Pompe disease can happen at any age, but in late-onset Pompe disease, symptoms generally start from 12 months old onwards.

The standard treatment for people with Pompe disease is to receive regular infusions of the GAA enzyme. This is known as enzyme replacement therapy. However, people can build up antibodies against the GAA enzyme over time.

Gene therapy is used to treat conditions caused by a faulty gene. It works by replacing the faulty gene with a working gene inside the cells of the body. The working gene is delivered into the cells using certain viruses as carriers (vectors). Viruses are often used as carriers as they can easily get inside cells. The genetic material of the original virus is replaced with the working gene, so only the working gene gets inside the cells. A common virus used as a carrier in gene therapy is the adeno-associated virus (or AAV). This is like an adenovirus, which causes the common cold.

The original type of AAV does not cause any harm to humans. However, people that have previously been infected with the original type of AAV may have built up antibodies against AAV. These antibodies may stop the AAV carrier with the working gene getting inside the cells.

Researchers want to learn more about antibody levels against AAV and the GAA enzyme in people with late-onset Pompe disease. They also want to learn about other substances in the blood that provide more information about late-onset Pompe disease. These are known as biomarkers.

In this study, older teenagers and adults with late-onset Pompe disease will take part. They will not have had gene therapy using AAV. There will be 2 groups - those who have never had enzyme replacement therapy, and those who have had enzyme replacement therapy for 6 months or more. No study treatment will be given during the study, but blood and urine samples will be taken for testing.

The main aims of the study are to check antibody levels against AAV8 (a type of AAV) in people with late-onset Pompe disease who had not received any treatment using AAV, to check antibody levels against the GAA enzyme in people previously treated with GAA as part of enzyme replacement therapy, to check levels of biomarkers for Pompe disease, and to check for medical problems.

In the study, people will visit the study clinic several times. Some visits may be in the person's home. The first visit is to check if they can take part. Those who can take part will have a medical examination, and have their vital signs checked. Vital signs include blood pressure, heart rate, breathing rate and temperature. Blood samples will be taken to check antibody levels against the GAA enzyme and against AAV8. Blood and urine samples will also be taken to check for biomarkers for Pompe disease. Blood and urine samples will be taken about every 4 months for up to 2 years.

Study Overview

• Status: Active, not recruiting
• Conditions: Pompe Disease (Late-onset)
• Intervention / Treatment: Other: No Intervention

Detailed Description

No investigational drug will be administered to participants in this study. Blood and urine will be collected as part of the study. The duration of the study is approximately 2 years, participants may withdraw at any time.

• Study Type: Interventional
• Enrollment (Actual): 119
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia
    • AU61003
  • Herston, Australia
    • AU61001
• Brazil
  • Flamengo, Brazil
    • BR55003
  • Porto Alegre, Brazil
    • BR55002
  • São Paulo, Brazil
    • BR55001
• Canada
  • Edmonton, Canada
    • CN15003
  • Montreal, Canada
    • CA15001
• France
  • Angers, France
    • FR33006
  • Garches, France
    • FR33009
  • Lille, France
    • FR33005
  • Limoges, France
    • FR33007
  • Marseille, France
    • FR33002
  • Nantes, France
    • FR33003
  • Nice, France
    • FR33004
  • Strasbourg, France
    • FR33001
• Germany
  • Bonn, Germany
    • DT49005
  • Essen, Germany
    • DT49004
  • Höchheim, Germany
    • DT49003
  • Münster, Germany
    • DT49006
• Italy
  • Florence, Italy
    • IT39002
  • Gussago, Italy
    • IT39005
  • Messina, Italy
    • IT39012
  • Milan, Italy
    • IT39009
  • Milan, Italy
    • IT39011
  • Pavia, Italy
    • IT39008
  • Pisa, Italy
    • IT39006
  • Roma, Italy
    • IT39004
  • Udine, Italy
    • IT39003
• Japan
  • Kodaira-Shi, Japan
    • National Center of Neurology and Psychiatry
  • Shinjuku-Ku, Japan
    • Tokyo Women's Medical University Hospital
• Spain
  • Albacete, Spain
    • ES34003
  • Barcelona, Spain
    • ES34004
  • Donostia / San Sebastian, Spain
    • ES34009
  • L'Hospitalet de Llobregat, Spain
    • ES34007
  • Madrid, Spain
    • ES34001
  • Madrid, Spain
    • ES34005
  • Valencia, Spain
    • ES34002
• Taiwan
  • Taipei, Taiwan
    • TW88601
  • Taipei, Taiwan
    • TW88602
  • Taoyuan, Taiwan
    • TW88603
• United Kingdom
  • Cambridge, United Kingdom
    • UK44003
  • Newcastle upon Tyne, United Kingdom
    • UK44001
  • Salford, United Kingdom
    • UK44004
• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Clinic
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Children's Hospitals and Clinics of Minnesota
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45221
      • University of Cincinnati
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of UTAH - PPDS
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Lysosomal and Rare Diseases Research and Treatment Center, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has a documented clinical diagnosis of LOPD.
• Participant is enzyme replacement therapy ERT-naïve (ERT-N) or if the participant is currently taking an approved ERT treatment or is participating in an ERT-interventional study, the ERT must have been received for at least 6 months or more (ERT-experienced [ERT-E]).
• Participant is willing and able to comply with study visits and procedures.
• Participant agrees to not start participating in any other clinical study involving an investigational study treatment, including ERT, while participating in this study.

Exclusion Criteria:

• Participant previously received an AAV-related product (any serotype).
• Participant is currently participating in a Pompe-related interventional study (other than ERT-interventional studies) or has received gene or cell therapy.
• Participant requires any invasive or noninvasive ventilation support while awake and upright (non-invasive support while sleeping with either continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) is acceptable for eligibility).
• Participant is unable to ambulate (assistive devices [e.g., cane or walker] are acceptable for eligibility).
• Participants who have received any ERT for less than 6 months as of the Baseline visit are not eligible.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Participants with Late-Onset Pompe Disease; Adolescent or adult participants with LOPD.	Other: No Intervention; No investigational drug will be administered to participants in this study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of total antibodies to AAV8	Antibodies to AAV8 will be recorded from serum blood samples collected.	Up to 2 years
Occurrence of neutralizing antibodies to AAV8	Antibodies to AAV8 will be recorded from serum blood samples collected.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seroconversion of antibodies to AAV8 over time	Seroconversion of antibodies to AAV8 will be recorded from serum blood samples collected.	Up to 2 years
Creatine kinase [CK] levels	CK levels will be recorded from blood plasma samples collected.	Up to 2 years
Urine glucose tetrasaccharide [Glc4]/hexose tetrasaccharide [Hex4] over time	Glc4/Hex4 will be recorded from urine samples collected.	Up to 2 years
Occurrence of anti-GAA antibodies in participants on ERT	Anti-GAA antibodies will be recorded from serum blood samples collected.	Up to 2 years

Collaborators and Investigators

• Sponsor: Astellas Gene Therapies
• Investigators: Study Director: Medical Director, Astellas Gene Therapies

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: November 21, 2023
• First Submitted That Met QC Criteria: November 21, 2023
• First Posted (Actual): November 29, 2023

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Biomarkers; Pompe Disease (Late-onset); Antibodies to AAV8
• 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
• Other Study ID Numbers: AT845-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

Drug and device information, study documents

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