Cipaglucosidase Alfa + Miglustat for Pompe Disease

Recruiting at 15 trial locations

Overseen By For Patient

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Amicus Therapeutics

Must be taking: ERT

Must not be taking: Gene therapy, Anabolic steroids

Disqualifiers: Pregnancy, Hypertrophic cardiomyopathy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

22 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 3, open-label, multicenter study to evaluate the safety, PK, efficacy, PD, and immunogenicity of Cipaglucosidase Alfa/Miglustat treatment in enzyme replacement therapy (ERT)-experienced and ERT-naïve pediatric subjects with Pompe disease, aged 0 to \< 18 years

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that you cannot have received any investigational drugs or certain prohibited medications within 30 days before screening. It's best to discuss your current medications with the trial team to see if they are allowed.

What data supports the effectiveness of the drug Cipaglucosidase Alfa + Miglustat for Pompe Disease?

Research shows that Cipaglucosidase Alfa combined with Miglustat improved walking distance and respiratory function in patients with Pompe disease over 48 months. In a study, patients who switched to this treatment showed significant improvements in motor skills and respiratory function, indicating its potential as an effective long-term treatment option. ^{1 2 3 4 5}

Is Cipaglucosidase Alfa + Miglustat safe for humans?

Cipaglucosidase Alfa combined with Miglustat has been studied for up to 48 months in people with Pompe disease and was generally well tolerated, showing a safety profile similar to an existing treatment called alglucosidase alfa. This means that the treatment did not cause unexpected or severe side effects in the study participants. ^{1 2 3 4 5}

How is the drug Cipaglucosidase Alfa + Miglustat unique for treating Pompe disease?

Cipaglucosidase Alfa + Miglustat is unique because it combines a new form of enzyme replacement therapy with an enzyme stabilizer, which improves the drug's effectiveness and uptake in the body. This combination has shown better results in improving muscle and respiratory function compared to previous treatments, especially in patients who did not respond well to existing therapies. ^{1 2 3 4 6}

Eligibility Criteria

This trial is for pediatric patients with Pompe disease, aged from birth to less than 18 years. It includes those who have previously received enzyme replacement therapy and those who haven't. Participants must meet certain breathing capacity criteria, agree to use contraception if of reproductive age, and not exceed a weight limit (for older children).

Inclusion Criteria

I can walk at least 75 meters if I'm 12-17 years old, or at least 40 meters if I'm 5-11 years old.

My lung function is at least 30% of what is expected for a healthy person my age.

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

Exclusion Criteria

I have a severe thickening of my heart muscle.

Subject has any intercurrent illness or condition at screening or baseline that may preclude the subject from fulfilling the protocol requirements or suggests to the investigator and/or the medical monitor that the potential subject may have an unacceptable risk by participating in this study

I was diagnosed with Pompe disease at birth and show no symptoms.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Cipaglucosidase Alfa (ATB200) co-administered with Miglustat (AT2221) for enzyme replacement therapy

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Cipaglucosidase Alfa
• Miglustat

Trial Overview The study tests the safety and effectiveness of Cipaglucosidase Alfa/Miglustat in treating Pompe disease in children. This Phase 3 trial involves both experienced and new patients to enzyme replacement therapy, assessing how the body processes the drug, its efficacy, pharmacodynamics, and potential immune response.

Participant Groups

Group I: Cipaglucosidase Alfa (ATB200)/Miglustat(AT2221) Experimental Treatment 2 Interventions

Participants received Cipaglucosidase Alfa (ATB200) co-administered with Miglustat (AT2221) capsule

Cipaglucosidase Alfa is already approved in European Union, United States for the following indications:

Approved in European Union as Pombiliti for:

• Late-onset Pompe disease (acid α-glucosidase [GAA] deficiency)

Approved in United States as Pombiliti for:

• Late-onset Pompe disease (acid α-glucosidase [GAA] deficiency)

Who Is Running the Clinical Trial?

Amicus Therapeutics

Lead Sponsor

Trials

55

Recruited

2,700+

Findings from Research

Cipaglucosidase alfa, a recombinant human enzyme, was approved in the EU as a long-term enzyme replacement therapy for adults with late-onset Pompe disease, a condition caused by a deficiency of the enzyme GAA.

This therapy is used in combination with miglustat, an enzyme stabilizer, marking a significant advancement in the treatment options available for this rare genetic disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cipaglucosidase Alfa: First Approval. Blair, HA.[2023]

Cipaglucosidase alfa combined with miglustat (cipa + mig) demonstrated significant improvements in six-minute walking distance over 48 months in both ambulatory and ERT-naïve cohorts, indicating its efficacy as a long-term treatment for Pompe disease.

The treatment was well tolerated, showing a safety profile similar to that of the existing enzyme replacement therapy, alglucosidase alfa, suggesting it could be a viable alternative for patients with Pompe disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of cipaglucosidase alfa plus miglustat in individuals living with Pompe disease: an open-label phase I/II study (ATB200-02). Byrne, BJ., Schoser, B., Kishnani, PS., et al.[2023]

In a phase 3 trial involving 125 patients with late-onset Pompe disease, the investigational therapy cipaglucosidase alfa plus miglustat did not show statistically significant improvement in 6-minute walk distance compared to alglucosidase alfa plus placebo after 52 weeks.

Despite similar rates of treatment-emergent adverse events between the two groups, the study suggests further investigation into the long-term safety and potential benefits of cipaglucosidase alfa plus miglustat, especially for patients who have been on enzyme replacement therapy for over 2 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo in late-onset Pompe disease (PROPEL): an international, randomised, double-blind, parallel-group, phase 3 trial. Schoser, B., Roberts, M., Byrne, BJ., et al.[2023]

Cipaglucosidase alfa, combined with Miglustat, has shown significant improvements in a patient with severe infantile Pompe disease, reversing serious symptoms like respiratory failure and cardiomyopathy, and restoring motor functions.

This new enzyme replacement therapy (ERT) proved more effective than the previous standard treatment, allowing the patient to regain motor skills, including head control and independent movement, highlighting its potential as a superior option for managing Pompe disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Enzyme Replacement Therapy with Cipaglucosidase Alfa/Miglustat in Infantile Pompe Disease. Fiege, L., Duran, I., Marquardt, T.[2023]

Avalglucosidase alfa, a new treatment for late-onset Pompe disease, was found to be well-tolerated in a study involving 23 patients over 24 weeks, with no deaths or life-threatening adverse events reported.

Exploratory efficacy results showed that patients' pulmonary function and functional capacity remained stable or improved, suggesting that avalglucosidase alfa may be effective in managing symptoms of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoGAA) in treatment-naïve and alglucosidase alfa-treated patients with late-onset Pompe disease: A phase 1, open-label, multicenter, multinational, ascending dose study. Pena, LDM., Barohn, RJ., Byrne, BJ., et al.[2020]

Miglustat, an oral medication developed for type 1 Gaucher disease, works by inhibiting glucosylceramide glucosyltransferase, which is crucial for managing this genetic disorder.

Approved in the EU in November 2002 and launched in the UK in March 2003, miglustat is also being explored for treating other glycolipid storage disorders, indicating its potential broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Miglustat. Oxford GlycoSciences/Actelion. Lachmann, RH.[2016]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Cipaglucosidase Alfa: First Approval. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of cipaglucosidase alfa plus miglustat in individuals living with Pompe disease: an open-label phase I/II study (ATB200-02). [2023]

3. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of cipaglucosidase alfa plus miglustat versus alglucosidase alfa plus placebo in late-onset Pompe disease (PROPEL): an international, randomised, double-blind, parallel-group, phase 3 trial. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Improved Enzyme Replacement Therapy with Cipaglucosidase Alfa/Miglustat in Infantile Pompe Disease. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoGAA) in treatment-naïve and alglucosidase alfa-treated patients with late-onset Pompe disease: A phase 1, open-label, multicenter, multinational, ascending dose study. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Miglustat. Oxford GlycoSciences/Actelion. [2016]