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

Pompe Disease (Late-onset) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06150820
• Other study ID #: AT845-02
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2024
• Est. completion date: May 31, 2027

Study information

• Verified date: June 2024
• Source: Astellas Pharma Inc
• Contact: Astellas Gene Therapies
• Phone: 800-888-7704
• Email: Astellas.registration[@]astellas.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: May 31, 2027
• Est. primary completion date: May 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 69 Years

Eligibility

Inclusion Criteria:

• Participant has a documented clinical diagnosis of LOPD.

• Participant is enzyme replacement therapy (ERT) naïve (ERT-N) or has received any ERT for 6 months or more (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.

Related Conditions & MeSH terms

• Glycogen Storage Disease Type II
• Pompe Disease (Late-onset)

Intervention

Other:
• No Intervention
No investigational drug will be administered to participants in this study.

Locations

Country	Name	City	State
Australia	AU61003	Adelaide
France	FR33006	Angers
France	FR33005	Lille
France	FR33007	Limoges
France	FR33002	Marseille
France	FR33003	Nantes
France	FR33004	Nice Cedex 3
France	FR33001	Strasbourg
Italy	IT39004	Roma
Spain	ES34003	Albacete
Spain	ES34006	Barcelona
Spain	ES34001	Madrid
Spain	ES34005	Madrid
Spain	ES34009	San Sebastian
Spain	ES34002	Valencia
Taiwan	TW88601	Taipei
Taiwan	TW88602	Taipei
Taiwan	TW88603	Taoyuan City
United States	Lysosomal and Rare Diseases Research and Treatment Center, Inc.	Fairfax	Virginia
United States	Children's Hospitals and Clinics of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Gene Therapies

Countries where clinical trial is conducted

United States,  Australia,  France,  Italy,  Spain,  Taiwan, 

Outcome

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