Clinical trial NCT06150820: A Study About Antibody Levels and Biomarkers in the Blood in People With Late-onset Pompe Disease
Official title: A Study to Evaluate Seroprevalence of Antibodies to AAV8 and Assessment of Biomarkers in Patients With Late-Onset Pompe Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Pompe Disease (Late-onset)
Keywords: Pompe Disease (Late-onset)
Antibodies to AAV8
Biomarkers
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2023-11-29
Enrollment: 100
Sex: ALL
Minimum age (years): 16
Maximum age (years): 69
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence of total antibodies to AAV8
timeFrame: Up to 2 years
measure: Occurrence of neutralizing antibodies to AAV8
timeFrame: Up to 2 years
Secondary outcomes:
measure: Seroconversion of antibodies to AAV8 over time
timeFrame: Up to 2 years
measure: Creatine kinase [CK] levels
timeFrame: Up to 2 years
measure: Urine glucose tetrasaccharide [Glc4]/hexose tetrasaccharide [Hex4] over time
timeFrame: Up to 2 years
measure: Occurrence of anti-GAA antibodies in participants on ERT
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Atlanta
country: United States
facility: Emory Clinic
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Minneapolis
country: United States
facility: Children's Hospitals and Clinics of Minnesota
state: Minnesota
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Fairfax
country: United States
facility: Lysosomal and Rare Diseases Research and Treatment Center, Inc.
state: Virginia
city: Adelaide
country: Australia
facility: AU61003
city: Herston
country: Australia
facility: AU61001
city: Porto Alegre
country: Brazil
facility: BR55002
city: Edmonton
country: Canada
facility: CN15003
city: Montreal
country: Canada
facility: CA15001
city: Angers
country: France
facility: FR33006
city: Garches
country: France
facility: FR33009
city: Lille
country: France
facility: FR33005
city: Limoges
country: France
facility: FR33007
city: Marseille
country: France
facility: FR33002
city: Nantes
country: France
facility: FR33003
city: Nice Cedex 3
country: France
facility: FR33004
city: Strasbourg
country: France
facility: FR33001
city: Bonn
country: Germany
facility: DT49005
city: Essen
country: Germany
facility: DT49004
city: Hochheim
country: Germany
facility: DT49003
city: Münster
country: Germany
facility: DT49006
city: Firenze
country: Italy
facility: IT39002
city: Gussago
country: Italy
facility: IT39005
city: Messina
country: Italy
facility: IT39012
city: Milano
country: Italy
facility: IT39009
city: Milano
country: Italy
facility: IT39011
city: Pavia
country: Italy
facility: IT39008
city: Pisa
country: Italy
facility: IT39006
city: Roma
country: Italy
facility: IT39004
city: Kodaira-Shi
country: Japan
facility: National Center of Neurology and Psychiatry
city: Shinjuku-Ku
country: Japan
facility: Tokyo Women's Medical University Hospital
city: Albacete
country: Spain
facility: ES34003
city: Barcelona
country: Spain
facility: ES34004
city: Barcelona
country: Spain
facility: ES34006
city: L'hospitalet de Llobregat
country: Spain
facility: ES34007
city: Madrid
country: Spain
facility: ES34001
city: Madrid
country: Spain
facility: ES34005
city: San Sebastian
country: Spain
facility: ES34009
city: Valencia
country: Spain
facility: ES34002
city: Taipei
country: Taiwan
facility: TW88601
city: Taipei
country: Taiwan
facility: TW88602
city: Taoyuan City
country: Taiwan
facility: TW88603
city: Cambridge
country: United Kingdom
facility: UK44003
city: Newcastle upon Tyne
country: United Kingdom
facility: UK44001
city: Salford
country: United Kingdom
facility: UK44004
Study officials:
affiliation: Astellas Gene Therapies
name: Medical Director
role: STUDY_DIRECTOR
References: