Gene Transfer for Pompe Disease

Recruiting at 30 trial locations

Overseen By Clinical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Spark Therapeutics, Inc.

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

4 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment called SPK-3006 for adults with late-onset Pompe disease who are already on enzyme replacement therapy. The treatment involves an infusion that delivers a gene to help produce a missing enzyme. The goal is to see if this new approach is safe and effective.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you have been on enzyme replacement therapy (ERT) for at least the past 24 months.

What data supports the effectiveness of the treatment SPK-3006 for Pompe Disease?

Research on gene therapy for Pompe disease in mice showed that delivering a modified version of the enzyme needed to break down glycogen improved muscle and heart function, reduced glycogen buildup, and increased survival. This suggests that gene transfer treatments like SPK-3006 could potentially be effective in treating Pompe disease. ^{1 2 3 4 5}

Is the gene therapy treatment for Pompe disease safe for humans?

Initial studies of the gene therapy using AAV8-LSPhGAA for late-onset Pompe disease showed no serious side effects related to the treatment, and it was safe to stop enzyme replacement therapy after a certain period. This supports the safety of the treatment in humans. ^{1 2 3 6 7}

How does the treatment SPK-3006 for Pompe disease differ from other treatments?

SPK-3006 is a gene therapy that uses a single infusion to deliver a vector for continuous production of the enzyme needed to treat Pompe disease, unlike enzyme replacement therapy which requires frequent infusions. This approach aims to improve efficacy by reducing immune responses and enhancing enzyme delivery to affected tissues, including the brain and muscles. ^{1 4 5 8 9}

Research Team

Tahseen Mozaffar, MD

Principal Investigator

University of California Irvine Health

Eligibility Criteria

Adults over 18 with moderate, late-onset Pompe disease who've been on enzyme replacement therapy (ERT) for at least 2 years can join. They must not be pregnant or nursing, have no active infections including hepatitis B/C and HIV, no history of liver cancer or significant liver disease, and agree to use contraception.

Inclusion Criteria

Agree to use reliable contraception

Provide written informed consent

I am 18 or older with late-onset Pompe disease.

Exclusion Criteria

You have antibodies in your body that could affect the study.

Pregnant or nursing women

You have a strong immune response to rhGAA.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intravenous infusion of SPK-3006

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• SPK-3006

Trial Overview The trial is testing SPK-3006's safety and effectiveness in adults with Pompe disease. It involves a single intravenous dose of the gene therapy drug given to different groups one after another at increasing dose levels while they continue their regular ERT.

Participant Groups

Group I: SPK-3006 Experimental Treatment 1 Intervention

All participants who meet the eligibility criteria will receive a single intravenous (i.v.) administration of SPK-3006.

Who Is Running the Clinical Trial?

Spark Therapeutics, Inc.

Lead Sponsor

Trials

16

Recruited

410+

Spark Therapeutics

Lead Sponsor

Trials

14

Recruited

350+

Findings from Research

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 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]

In a 52-week study involving 3 patients with late-onset Pompe disease, gene therapy using the AAV8 vector showed promising safety and bioactivity, allowing subjects to discontinue enzyme replacement therapy (ERT) after 26 weeks without serious adverse events.

All participants exhibited sustained increases in serum GAA activity and significant improvements in muscle GAA activity by week 52, indicating that AAV8-LSPhGAA could effectively replace ERT and warrants further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of liver depot gene therapy in late-onset Pompe disease. Smith, EC., Hopkins, S., Case, LE., et al.[2023]

Gene therapy for Pompe disease, using an adeno-associated virus (AAV) vector, has shown promise in early clinical trials by providing a single infusion that allows the liver to continuously produce the enzyme GAA, potentially surpassing the need for frequent enzyme replacement therapy (ERT).

This gene therapy not only corrects GAA deficiency and reduces glycogen accumulation in the heart and skeletal muscle but also induces immune tolerance to GAA, which may enhance its effectiveness compared to traditional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver depot gene therapy for Pompe disease. Kishnani, PS., Koeberl, DD.[2020]

References

1. United States pubmed.ncbi.nlm.nih.gov

Neuroimaging findings in infantile Pompe patients treated with enzyme replacement therapy. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

A beta-blocker, propranolol, decreases the efficacy from enzyme replacement therapy in Pompe disease. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Screening chimeric GAA variants in preclinical study results in hematopoietic stem cell gene therapy candidate vectors for Pompe disease. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Rescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid α-glucosidase. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Phase I study of liver depot gene therapy in late-onset Pompe disease. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Immune responses and hypercoagulation in ERT for Pompe disease are mutation and rhGAA dose dependent. [2021]

8. China pubmed.ncbi.nlm.nih.gov

Liver depot gene therapy for Pompe disease. [2020]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Advancements in AAV-mediated Gene Therapy for Pompe Disease. [2020]