ACTUS-101 for Pompe Disease

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

7 Participants Needed

Trial Summary

What is the purpose of this trial?

Open-label, ascending dose trial of ACTUS-101 administered intravenously.

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.

What data supports the effectiveness of the treatment AAV2/8-LSPhGAA, ACTUS-101 for Pompe Disease?

A study on a similar treatment, AAV8-LSPhGAA, showed that it increased enzyme activity in the blood and muscle of patients with late-onset Pompe disease, suggesting it might help manage the condition. The study also found no serious side effects, supporting its safety. ^{1 2 3 4 5}

How is the treatment ACTUS-101 for Pompe Disease different from other treatments?

ACTUS-101 uses a gene therapy approach with an adeno-associated virus (AAV) to deliver a gene that helps the liver produce the enzyme needed to break down glycogen, potentially eliminating the need for regular enzyme replacement therapy (ERT). This is different from traditional treatments that require frequent ERT infusions. ^{1 2 3 4 6}

Research Team

Edward Smith, MD

Principal Investigator

Duke University

Eligibility Criteria

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

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

Pregnant or nursing mothers

You have signs of being exposed to HIV or having active hepatitis A, B, or C infection.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

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

Clinical characteristics and genotypes in the ADVANCE baseline data set, a comprehensive cohort of US children and adolescents with Pompe disease. [2022]

2. United States 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. [2023]

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

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

5. England 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. [2022]

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

A randomized study of alglucosidase alfa in late-onset Pompe's disease. [2022]