Antibody Levels and Biomarkers for Pompe Disease

Not currently recruiting at 65 trial locations

Overseen By Astellas Gene Therapies

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Astellas Gene Therapies

Must be taking: Enzyme replacement

Disqualifiers: AAV therapy, Gene therapy, Ventilation support, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies antibody levels and other blood markers in individuals with late-onset Pompe disease, a condition that causes muscle weakness due to a genetic issue. Researchers aim to observe the body's response to standard enzyme replacement therapy and to learn more about antibodies against the treatment and the virus used in gene therapy. Participants will not receive new treatment but will provide blood and urine samples regularly for up to two years. The trial includes teenagers and adults diagnosed with late-onset Pompe disease who have either never received enzyme replacement therapy or have been on it for at least six months. As an unphased trial, this study offers a unique opportunity to enhance the understanding of Pompe disease and its treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on enzyme replacement therapy (ERT), you must have been on it for at least 6 months to participate.

What prior data suggests that this study's methods are safe?

In a previous study, researchers found that the original type of adeno-associated virus (AAV) used in gene therapy is safe for humans. This virus often delivers healthy genes into cells because it can easily enter them. However, some people might have antibodies against AAV if they have been exposed to it before, which could prevent the therapy from working properly.

For enzyme replacement therapy, the current standard treatment for Pompe disease, some patients develop antibodies against the enzyme they receive, affecting the treatment's effectiveness over time. Researchers aim to learn more about these antibodies and other substances in the blood, called biomarkers, which can provide more information about Pompe disease.

In this study, no treatment is given, so there are no safety concerns from interventions. Researchers will only collect blood and urine samples to study these antibodies and biomarkers. Participants won't face risks from new treatments in this study.

Why are researchers excited about this trial?

Researchers are excited about this trial for Pompe disease because it aims to uncover important details about antibody levels and biomarkers in patients with late-onset Pompe disease (LOPD). Unlike standard treatments that focus on enzyme replacement therapies, this study seeks to enhance our understanding of the disease at a molecular level. By identifying specific biomarkers, scientists hope to improve diagnostic methods and potentially develop more targeted and effective treatments in the future. This approach could lead to better management strategies and ultimately improve the quality of life for those affected by LOPD.

What evidence suggests that this study's methods could be effective for understanding antibody levels and biomarkers in late-onset Pompe disease?

Research has shown that Pompe disease results from a faulty gene, causing muscle weakness due to glycogen (a type of sugar) build-up in cells. The usual treatment, enzyme replacement therapy, involves infusions of the missing enzyme. However, the body can sometimes develop antibodies against this enzyme, reducing the treatment's effectiveness over time. Gene therapy is a new method that aims to fix the faulty gene by using viruses to deliver a working version of the gene. Researchers are still studying this approach, especially in individuals who have not previously received gene therapy. This trial focuses on participants with Late-Onset Pompe Disease to learn more about the levels of antibodies against these carriers and the enzyme, which could help improve treatment for Pompe disease.

Who Is on the Research Team?

Medical Director

Principal Investigator

Astellas Gene Therapies

Are You a Good Fit for This Trial?

This study is for older teens and adults with late-onset Pompe disease, a condition causing muscle weakness. Participants either have never had enzyme replacement therapy or have been on it for at least 6 months. They must be able to attend study visits and agree not to join other clinical trials during this one.

Inclusion Criteria

I have never had enzyme replacement therapy or have been on it for 6+ months.

I have been diagnosed with Late-Onset Pompe Disease (LOPD).

You promise not to join any other research studies with new treatments while you are in this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Baseline Assessment

Participants undergo a medical examination and have their vital signs checked. Blood and urine samples are taken to check antibody levels and biomarkers.

1 visit

1 visit (in-person)

Monitoring

Blood and urine samples are collected approximately every 4 months to monitor antibody levels and biomarkers.

Up to 2 years

Visits every 4 months (in-person or at home)

Follow-up

Participants are monitored for any medical problems and changes in antibody levels and biomarkers.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• No Intervention

Trial Overview The study isn't testing a new treatment but is looking at antibody levels against AAV8 (a harmless virus used in gene therapy) and the GAA enzyme involved in standard Pompe disease treatment. It also measures biomarkers related to the disease through regular blood and urine tests over two years.

How Is the Trial Designed?

Group I: Participants with Late-Onset Pompe Disease Experimental Treatment 1 Intervention

Adolescent or adult participants with LOPD.

Who Is Running the Clinical Trial?

Astellas Gene Therapies

Lead Sponsor

Trials

7

Recruited

400+

Published Research Related to This Trial

Out of 344,056 newborns screened since 2005, 13 were identified with later-onset Pompe disease, demonstrating that newborn screening effectively facilitates early detection of this condition.

Early treatment was initiated for four patients based on symptoms like hypotonia and muscle weakness, highlighting the importance of monitoring motor development and serum creatine kinase levels for timely intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Later-onset Pompe disease: early detection and early treatment initiation enabled by newborn screening. Chien, YH., Lee, NC., Huang, HJ., et al.[2022]

In a study involving 8 infants with infantile-onset Pompe disease, treatment with recombinant human acid alpha-glucosidase (rhGAA) for 52 weeks resulted in improved survival rates, with 6 out of 8 patients alive and 5 free from invasive ventilator support by the end of the study.

The treatment was found to be safe and well tolerated, leading to significant clinical improvements in cardiomyopathy, growth, and motor function, with patients achieving new motor milestones and a median age at death or treatment withdrawal of 21.7 months, which is significantly later than expected for untreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease. Kishnani, PS., Nicolino, M., Voit, T., et al.[2022]

Avalglucosidase alfa demonstrated a positive clinical effect in individuals with infantile-onset Pompe disease who had previously shown clinical decline on alglucosidase alfa, with trends indicating improved motor function, especially at the 40 mg/kg dose.

The study, involving 22 participants over a 25-week period, reported high treatment compliance (100%) and no serious treatment-related adverse events, suggesting that avalglucosidase alfa is safe and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of avalglucosidase alfa in individuals with infantile-onset Pompe disease enrolled in the phase 2, open-label Mini-COMET study: The 6-month primary analysis report. Kishnani, PS., Kronn, D., Brassier, A., et al.[2023]

In a study of 243 patients with infantile Pompe disease, 25.1% were identified as CRIM-negative, which is associated with poor response to enzyme replacement therapy (ERT) due to high antibody levels against the treatment.

Understanding a patient's CRIM status, which can often be predicted from GAA gene mutations, is crucial before starting ERT, as it can guide immunomodulation strategies to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting cross-reactive immunological material (CRIM) status in Pompe disease using GAA mutations: lessons learned from 10 years of clinical laboratory testing experience. Bali, DS., Goldstein, JL., Banugaria, S., et al.[2022]

Newborn screening for classic infantile-onset Pompe disease (IOPD) allows for early treatment with recombinant human acid α-glucosidase (rhGAA), leading to positive long-term outcomes such as independent walking and no need for mechanical ventilation in all patients studied.

After a median treatment duration of 63 months, while patients showed good motor function and daily activity participation, some experienced gradual muscle weakness and common speech disorders, indicating that while rhGAA is effective, there are still limitations and ongoing challenges in managing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term prognosis of patients with infantile-onset Pompe disease diagnosed by newborn screening and treated since birth. Chien, YH., Lee, NC., Chen, CA., et al.[2022]

Enzyme replacement therapy (ERT) for adults with late-onset Pompe disease showed significant improvements in walking distance and muscle strength over the first two years of treatment, based on a study of 62 patients.

However, ERT did not demonstrate a statistically significant impact on respiratory function or body mass index, indicating that while ERT is effective for certain outcomes, it may not address all aspects of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of enzyme replacement therapy in adults with late-onset Pompe disease: results from the NCS-LSD cohort study. Anderson, LJ., Henley, W., Wyatt, KM., et al.[2022]

In a study of 23 infants with infantile Pompe disease (IPD), 70% showed neuroimaging abnormalities at baseline, but many of these issues, such as ventricular enlargement and cerebrospinal fluid accumulation, improved significantly with enzyme replacement therapy (ERT) over time.

Follow-up imaging revealed emerging white matter changes in some older patients, highlighting the need for ongoing neuroimaging to monitor potential complications like cerebral aneurysms in patients receiving ERT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuroimaging findings in infantile Pompe patients treated with enzyme replacement therapy. McIntosh, PT., Hobson-Webb, LD., Kazi, ZB., et al.[2022]

In a study of 6 Hungarian patients with Pompe disease receiving enzyme replacement therapy (ERT), it was found that treatment led to increased activation of T cells, indicating a pro-inflammatory immune response.

The therapy also resulted in a dose-dependent increase in interferon-gamma (IFN-γ) production from T cells, suggesting that while ERT is effective, it may provoke immune responses that could interfere with its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzyme replacement therapy induces T-cell responses in late-onset Pompe disease. Banati, M., Hosszu, Z., Trauninger, A., et al.[2011]

In a study of 25 patients with late onset Pompe disease treated with enzyme replacement therapy (ERT), 72% developed antibodies against the treatment, but these antibodies did not significantly affect clinical outcomes over one year.

Patients with low to intermediate antibody titers showed no differences in muscle function, respiratory performance, or muscle imaging results compared to those without antibodies, suggesting that these antibody levels may not impact the efficacy of ERT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study of the effect of anti-rhGAA antibodies at low and intermediate titers in late onset Pompe patients treated with ERT. Fernández-Simón, E., Carrasco-Rozas, A., Gallardo, E., et al.[2020]

In a study of 168 patients with infantile-onset Pompe disease, the median age for symptom onset was 2 months, with a high mortality rate; only 25.7% survived past 12 months and 12.3% were ventilator-free.

Key symptoms such as cardiomegaly, hypotonia, and respiratory distress typically appeared around 4 months of age, and early symptom onset was linked to a higher risk of early death, highlighting the severe nature of this condition despite treatment efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. Kishnani, PS., Hwu, WL., Mandel, H., et al.[2022]

Citations