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

Not Applicable
Recruiting
Conditions
Pompe Disease (Late-onset)
Interventions
Other: No Intervention
Registration Number
NCT06150820
Lead Sponsor
Astellas Gene Therapies
Brief Summary

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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
100
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Participants with Late-Onset Pompe DiseaseNo InterventionAdolescent or adult participants with LOPD.
Primary Outcome Measures
NameTimeMethod
Occurrence of total antibodies to AAV8Up to 2 years

Antibodies to AAV8 will be recorded from serum blood samples collected.

Occurrence of neutralizing antibodies to AAV8Up to 2 years

Antibodies to AAV8 will be recorded from serum blood samples collected.

Secondary Outcome Measures
NameTimeMethod
Seroconversion of antibodies to AAV8 over timeUp to 2 years

Seroconversion of antibodies to AAV8 will be recorded from serum blood samples collected.

Creatine kinase [CK] levelsUp to 2 years

CK levels will be recorded from blood plasma samples collected.

Urine glucose tetrasaccharide [Glc4]/hexose tetrasaccharide [Hex4] over timeUp to 2 years

Glc4/Hex4 will be recorded from urine samples collected.

Occurrence of anti-GAA antibodies in participants on ERTUp to 2 years

Anti-GAA antibodies will be recorded from serum blood samples collected.

Trial Locations

Locations (51)

DT49006

🇩🇪

Münster, Germany

IT39006

🇮🇹

Pisa, Italy

FR33003

🇫🇷

Nantes, France

FR33004

🇫🇷

Nice Cedex 3, France

FR33001

🇫🇷

Strasbourg, France

DT49005

🇩🇪

Bonn, Germany

DT49004

🇩🇪

Essen, Germany

DT49003

🇩🇪

Hochheim, Germany

IT39002

🇮🇹

Firenze, Italy

IT39005

🇮🇹

Gussago, Italy

IT39012

🇮🇹

Messina, Italy

IT39009

🇮🇹

Milano, Italy

IT39011

🇮🇹

Milano, Italy

IT39008

🇮🇹

Pavia, Italy

IT39004

🇮🇹

Roma, Italy

University of California Irvine

🇺🇸

Irvine, California, United States

Emory Clinic

🇺🇸

Atlanta, Georgia, United States

University of Kansas Medical Center

🇺🇸

Kansas City, Kansas, United States

University of Michigan

🇺🇸

Ann Arbor, Michigan, United States

Children's Hospitals and Clinics of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

University of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

🇺🇸

Pittsburgh, Pennsylvania, United States

Lysosomal and Rare Diseases Research and Treatment Center, Inc.

🇺🇸

Fairfax, Virginia, United States

AU61003

🇦🇺

Adelaide, Australia

AU61001

🇦🇺

Herston, Australia

BR55002

🇧🇷

Porto Alegre, Brazil

CN15003

🇨🇦

Edmonton, Canada

CA15001

🇨🇦

Montreal, Canada

FR33006

🇫🇷

Angers, France

FR33009

🇫🇷

Garches, France

FR33005

🇫🇷

Lille, France

FR33007

🇫🇷

Limoges, France

FR33002

🇫🇷

Marseille, France

National Center of Neurology and Psychiatry

🇯🇵

Kodaira-Shi, Japan

Tokyo Women's Medical University Hospital

🇯🇵

Shinjuku-Ku, Japan

ES34003

🇪🇸

Albacete, Spain

ES34004

🇪🇸

Barcelona, Spain

ES34006

🇪🇸

Barcelona, Spain

ES34007

🇪🇸

L'hospitalet de Llobregat, Spain

ES34001

🇪🇸

Madrid, Spain

ES34005

🇪🇸

Madrid, Spain

ES34009

🇪🇸

San Sebastian, Spain

ES34002

🇪🇸

Valencia, Spain

TW88601

🇨🇳

Taipei, Taiwan

TW88602

🇨🇳

Taipei, Taiwan

TW88603

🇨🇳

Taoyuan City, Taiwan

UK44003

🇬🇧

Cambridge, United Kingdom

UK44001

🇬🇧

Newcastle upon Tyne, United Kingdom

UK44004

🇬🇧

Salford, United Kingdom

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