ACTUS-101 for Pompe Disease

Not currently recruiting at 2 trial locations

Overseen By AskFirst Patient Engagement

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AskBio Inc

Must be taking: ERT

Disqualifiers: Invasive ventilation, Active infection, HIV, others

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

Compensation: Varies

Number of Visits: 79

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ACTUS-101 (also known as AAV2/8-LSPhGAA) for individuals with Pompe disease, a genetic disorder affecting muscle function. The goal is to determine the safety of different doses of ACTUS-101 and their impact on the disease. Participants will receive a one-time infusion of ACTUS-101 at varying dose levels. Suitable candidates have been diagnosed with Pompe disease, can walk at least 100 meters with or without assistance, and have undergone enzyme replacement therapy (ERT) for at least two years before the trial. 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 treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must have been on a stable dose of enzyme replacement therapy (ERT) for at least 52 weeks before starting the trial.

Is there any evidence suggesting that ACTUS-101 is likely to be safe for humans?

Research has shown that ACTUS-101, a gene therapy for Pompe disease, demonstrates promising safety results. In previous studies, researchers delivered this treatment using a virus (AAV8) to carry the therapy into the body. This method appears safe and effective for individuals with Pompe disease. The treatment aims to correct a specific protein issue in these patients.

So far, studies have not reported any major safety concerns. The treatment is well-tolerated, with most participants not experiencing serious side effects. This is encouraging, suggesting that ACTUS-101 could be a safe option for those considering this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ACTUS-101 for Pompe disease because it offers a new approach that differs from current treatments like enzyme replacement therapy (ERT). Unlike ERT, which requires regular infusions, ACTUS-101 is delivered as a one-time intravenous infusion using a gene therapy method. It utilizes an adeno-associated virus (AAV2/8) to deliver the gene responsible for producing the enzyme that people with Pompe disease lack. This innovative delivery could potentially provide a more sustained therapeutic effect, reducing the need for frequent treatments and improving patient quality of life.

What evidence suggests that ACTUS-101 might be an effective treatment for Pompe Disease?

Research shows that ACTUS-101, a gene therapy, could be promising for treating Pompe disease. It uses a viral vector to deliver genes, helping the liver produce an enzyme that people with Pompe disease lack. Studies suggest this method might reduce the need for regular enzyme replacement therapy, the current standard treatment. Early results indicate that even small doses could lead to the desired changes in the body. This trial will test different dose levels of ACTUS-101, with participants receiving a one-time intravenous infusion in one of the study's cohorts. This treatment could potentially improve the quality of life for people with Pompe disease. ^{4 5 6 7 8}

Who Is on the Research Team?

Edward Smith, MD

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Pompe disease, confirmed by specific tests and genetic markers. Participants must be able to walk at least 100 meters and have been on enzyme replacement therapy (ERT) for two years, with a stable dose in the last year. They should have certain lung function levels but can't join if they've used other investigational drugs recently, started or stopped respiratory training near enrollment, have certain infections or liver disease, are pregnant/nursing, need invasive ventilation, or had a live vaccine recently.

Inclusion Criteria

I have been diagnosed with Pompe disease through a blood or skin test.

I can sign and understand the consent form.

I have LOPD and have been on ERT for at least 2 years, with a stable dose for the last year.

Exclusion Criteria

Pregnant or nursing mothers

Received an investigational drug or participated in another interventional study within 90 days prior to Study Day 1. Additionally, subjects cannot participate in any other interventional clinical trial throughout the first 78 weeks after receiving ACTUS-101

I need a machine to help me breathe, either through a mask or a tube.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time intravenous infusion of ACTUS-101 at varying dose levels

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of GAA bioactivity, muscle status, pulmonary function, and antibody formation

78 weeks

Regular visits (in-person and virtual) over 78 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AAV2/8-LSPhGAA
• ACTUS-101

Trial Overview The trial is testing ACTUS-101 given through an IV. It's an open-label study where everyone knows what treatment they're getting. The doses will increase to see how much can be given safely. This is for people who already use standard treatments like ERT but still need help managing their condition.

How Is the Trial Designed?

Group I: Cohort 3 Experimental Treatment 1 Intervention

A one-time intravenous infusion of ACTUS-101 (dose level 3)

Group II: Cohort 2 Experimental Treatment 1 Intervention

A one-time intravenous infusion of ACTUS-101 (dose level 2)

Group III: Cohort 1 Experimental Treatment 1 Intervention

A one-time intravenous infusion of ACTUS-101 (dose level 1)

Who Is Running the Clinical Trial?

AskBio Inc

Lead Sponsor

Trials

8

Recruited

440+

Asklepios Biopharmaceutical, Inc.

Lead Sponsor

Trials

8

Recruited

440+

Published Research Related to This Trial

In a phase 3 trial involving 100 participants with late-onset Pompe disease, avalglucosidase alfa demonstrated a significant improvement in respiratory function (measured by forced vital capacity) compared to the standard treatment, alglucosidase alfa, with a mean difference of 2.43%.

Avalglucosidase alfa also showed better outcomes in functional endurance (measured by the 6-minute walk test), indicating its potential as a more effective treatment option without new safety concerns compared to the existing therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of avalglucosidase alfa versus alglucosidase alfa in patients with late-onset Pompe disease (COMET): a phase 3, randomised, multicentre trial. Diaz-Manera, J., Kishnani, PS., Kushlaf, H., 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 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. scge.mcw.edu scge.mcw.edu/platform/data/clinicalTrials/report/NCT03533673

AAV2/8-LSPhGAA (ACTUS-101) in Late-Onset Pompe ... Screening data from 19 patients with late-onset Pompe disease for a phase I ... Minimum Effective Dose to Achieve Biochemical Correction with Adeno ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5363303/

Low-Dose Liver-Targeted Gene Therapy for Pompe ... The present study compared the efficacy of ERT against gene transfer with an adeno-associated viral (AAV) vector containing a liver-specific promoter. GAA ...

3. cell.com cell.com/molecular-therapy-family/molecular-therapy/pdf/S1525-0016(23)00077-1.pdf

Phase I study of liver depot gene therapy in late-onset ... Gene therapy with an adeno-associated virus serotype 8 (AAV8) vector (AAV8-LSPhGAA) could eliminate the need for enzyme.

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

New horizons in understanding and treating Pompe disease NCT03533673 AAV2/8-LSPhGAA (ACTUS-101) active. Phase 1. Prospective, open-label trial designed to objectively assess the safety and ...

5. askbio.com askbio.com/first-patient-dosed-with-gene-therapy-in-phase-1-2-study-of-actus-101-in-patients-with-pompe-disease/

First Patient Dosed with Gene Therapy in Phase 1/2 Study ... Initial clinical study to evaluate ACTUS-101 over 52 weeks that could improve quality of life for those who are affected with rare genetic disorder – Pompe ...

6. cgtlive.com cgtlive.com/view/askbio-evaluates-actus-101-gene-therapy-late-onset-pompe

AskBio Evaluates ACTUS-101 Gene Therapy for Late- ... ACTUS-101 is an adeno-associated virus (AAV) gene therapy that aims to address the deficiency of acid-alpha-glucosidase (GAA) in patients with Pompe disease.

7. rarediseaseadvisor.com rarediseaseadvisor.com/news/potential-gene-therapy-pompe-disease-yields-promising-results-trial/

Phase 1 Trial Results for Pompe Disease Gene Therapy ... A potential gene therapy with an adeno-associated virus serotype 8 vector (AAV8-LSPhGAA) seems to be safe and bioactive in Pompe disease.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1525001623000771

Phase I study of liver depot gene therapy in late-onset ... Gene therapy with an adeno-associated virus serotype 8 (AAV8) vector (AAV8-LSPhGAA) could eliminate the need for enzyme replacement therapy ...