Cipaglucosidase Alfa + Miglustat for Pompe Disease

Not currently recruiting at 18 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment option for Pompe disease, a condition affecting muscle function and strength. The study examines the safety and effectiveness of combining two drugs, Cipaglucosidase Alfa (an enzyme replacement therapy) and Miglustat, for children who may or may not have tried other enzyme replacement therapies. Children with Pompe disease who can walk at least 75 meters in six minutes and weigh 115 kg or less might qualify for this study. The goal is to determine if this treatment can improve symptoms and quality of life for participants. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that Cipaglucosidase Alfa and Miglustat are likely to be safe for humans?

Research has shown that the combination of Cipaglucosidase Alfa and Miglustat has been tested in adults with Pompe disease for over two years. In these studies, most participants tolerated the treatment well. Many experienced improvement or stability in their condition, suggesting the treatment's potential safety. However, individual experiences can vary, and some may encounter side effects.

The FDA has approved the treatment for certain adults, providing some confidence in its safety. Since this study focuses on a younger group, discussing any concerns with a healthcare provider is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Pompe disease?

Researchers are excited about Cipaglucosidase Alfa combined with Miglustat for Pompe Disease because it represents a novel approach in treatment. Unlike current standard therapies like enzyme replacement therapy (ERT) with alglucosidase alfa, this combination uses Cipaglucosidase Alfa, which is designed to be more efficiently taken up by cells. Additionally, Miglustat acts as a chaperone to stabilize and enhance the activity of Cipaglucosidase Alfa, potentially leading to improved efficacy in breaking down glycogen. This dual mechanism could offer better outcomes for patients by addressing the underlying enzyme deficiency more effectively.

What evidence suggests that Cipaglucosidase Alfa + Miglustat might be an effective treatment for Pompe disease?

Research has shown that the combination of Cipaglucosidase Alfa and Miglustat, which participants in this trial will receive, may help treat Pompe disease. In one study, patients who received this treatment walked an average of 17 meters further after 52 weeks, indicating better mobility. This treatment helps cells break down waste properly, reducing symptoms like muscle weakness and breathing problems. Overall, these findings suggest that this treatment could improve the quality of life for people with Pompe disease. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. ir.amicusrx.com ir.amicusrx.com/news-releases/news-release-details/new-4-year-data-pombilitir-cipaglucosidase-alfa-atga-opfoldar

New 4-Year Data for Pombiliti® (cipaglucosidase alfa-atga) ... After 52 weeks, ERT-experienced patients treated with cipaglucosidase alfa-atga + miglustat (n=61) walked an estimated 17 meters (95% CI, 0.2, ...

2. ir.amicusrx.com ir.amicusrx.com/news-releases/news-release-details/new-analysis-pombilitir-cipaglucosidase-alfa-atga-opfoldar

New Analysis of Pombiliti® (cipaglucosidase alfa-atga) ... Patients remaining on alglucosidase alfa + pbo demonstrated statistically significant worsening for several lung function outcomes, biomarker ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2772632024000138

Unveiling new horizons in Pompe disease therapy This drug aims to restore the normal physiological function of lysosomes, thereby mitigating the impact of Pompe disease on affected individuals.

4. pombilitiopfolda.com pombilitiopfolda.com/

Learn About POMBILITI® (cipaglucosidase alfa-atga) + ... Learn about an FDA-approved two-component therapy option for certain adults. See how it works, view the trial results, and access support and resources.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11426283/

Comparing the efficacy of cipaglucosidase alfa plus ... These two outcomes capture the key Pompe disease manifestations of impaired motor and pulmonary function and served as either the primary or key ...

6. pombilitiopfoldahcp.com pombilitiopfoldahcp.com/clinical-data

Study Results for POMBILITI® (cipaglucosidase alfa-atga) + ... 104-week efficacy and safety of cipglucosidase alfa plus miglustat in adults with late-onset Pompe disease: a phase III open-label extension study (ATB200-07).

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38418563/

104-week efficacy and safety of cipaglucosidase alfa plus ... Cipa + mig treatment up to 104 weeks was associated with overall maintained improvements (6MWD, biomarkers) or stabilization (FVC) from baseline with continued ...