Gene Transfer for Pompe Disease

Not currently recruiting at 34 trial locations

Overseen By Clinical Director

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Spark Therapeutics, Inc.

Must be taking: Enzyme replacement

Disqualifiers: Hepatitis, HIV, Liver disease, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy treatment called SPK-3006 for adults with late-onset Pompe disease. The goal is to determine if a single infusion of SPK-3006 is safe, well-tolerated, and effective for those already relying on enzyme replacement therapy (ERT). It targets individuals who have been on ERT for at least two years and have clinically moderate symptoms of Pompe disease, which affects muscle strength and breathing. Participants will receive the treatment at different dose levels to identify the most effective one. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that SPK-3006 is likely to be safe for humans?

Research has shown that SPK-3006 is being explored as a new treatment for late-onset Pompe disease, which affects how the body processes sugar and leads to muscle issues. Early studies indicate that SPK-3006 is a gene therapy delivered through a single IV infusion.

Patients have generally tolerated SPK-3006 well, with no major safety concerns reported in these early studies. While some minor side effects might occur, most people manage the treatment without serious problems. Since the trial is in its early stages, the main goal is to ensure the treatment's safety. This phase suggests that SPK-3006 appears safe in humans, but further research is needed to confirm these results. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about SPK-3006 for Pompe Disease because it uses a cutting-edge gene transfer approach. Unlike current treatments that typically involve enzyme replacement therapy, SPK-3006 delivers a functional copy of the defective gene directly to the patient's cells via a single intravenous administration. This method aims to enable the body to produce its own enzymes, potentially providing a longer-lasting and more effective solution. The excitement lies in its potential to address the root cause of Pompe Disease rather than just managing the symptoms.

What evidence suggests that SPK-3006 might be an effective treatment for Pompe disease?

Research has shown that SPK-3006, a gene therapy, could be a promising treatment for late-onset Pompe disease. In studies with mice, the treatment completely reversed the disease's symptoms. SPK-3006 uses a virus to deliver a healthy version of a gene that helps break down glycogen, a type of sugar. In people with Pompe disease, glycogen accumulates, causing muscle weakness and other issues. This new therapy aims to provide a longer-lasting solution compared to current treatments, which mainly slow the disease's progression. Early results suggest that SPK-3006 could improve muscle strength and overall quality of life for those with this condition. Participants in this trial will receive a single intravenous (i.v.) administration of SPK-3006. ^{1 2 3 6 7}

Who Is on the Research Team?

Tahseen Mozaffar, MD

Principal Investigator

University of California Irvine Health

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04093349

NCT04093349 | A Gene Transfer Study for Late-Onset ... The purpose of this study is to evaluate the safety, tolerability, and efficacy of a single intravenous infusion of SPK-3006 in adults with clinically moderate, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9759116/

Therapeutic Options for the Management of Pompe Disease Although the treatment has improved many aspects of the disease, such as prolonged survival through improved cardiomyopathy and acquisition of ...

3. nmd-journal.com nmd-journal.com/article/S0960-8966(19)30412-2/fulltext

O.6Pre-clinical development of SPK-3006, an investigational ... Enzyme replacement therapy (ERT) increases survival, slows disease progression, and is the current standard of care for Pompe disease patients. However, ERT has ...

4. clinicaltrials.eu clinicaltrials.eu/inn/vanglusagene-ensiparvovec/

Vanglusagene Ensiparvovec – Application in Therapy and ... Vanglusagene Ensiparvovec, also known as SPK-3006, is an investigational gene therapy being studied for the treatment of Late-Onset Pompe Disease (LOPD).

5. researchgate.net researchgate.net/publication/336190774_O6Pre-clinical_development_of_SPK-3006_an_investigational_liver-directed_AAV_gene_therapy_for_the_treatment_of_Pompe_disease

(PDF) O.6Pre-clinical development of SPK-3006, an ... We previously reported full rescue of Pompe disease in symptomatic four-month-old Gaa-/- mice by adeno-associated virus (AAV) vector-mediated ...

6. jpccr.eu jpccr.eu/pdf-193653-119773?filename=New%20Horizons%20in.pdf

New horizons in understanding and treating Pompe disease Pompe disease (PD), also known as glycogenosis type II or acidic maltase deficiency, is a rare genetic and metabolic disease caused by an ...

7. withpower.com withpower.com/trial/phase-2-glycogen-storage-disease-9-2020-c76f0

Gene Transfer for Pompe Disease · Info for Participants This trial is testing a new treatment called SPK-3006 for adults with late-onset Pompe disease who are already on enzyme replacement therapy.