Cipaglucosidase Alfa + Miglustat for Pompe Disease

(ROSSELLA Trial)

Recruiting at 17 trial locations

Overseen By For Site

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Amicus Therapeutics

Must be taking: ERT

Must not be taking: Iminosugars

Disqualifiers: Invasive ventilation, CRIM negative, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 3, open-label, multicenter study to evaluate the safety, efficacy, PK, PD, and immunogenicity of cipaglucosidase alfa/miglustat treatment in ERT-experienced and ERT-naïve pediatric subjects with IOPD.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are already on enzyme replacement therapy (ERT), you must have been on a stable dose for at least 3 months before joining the trial.

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 health, indicating its potential as an effective long-term therapy. ^{1 2 3 4 5}

Is Cipaglucosidase Alfa + Miglustat safe for humans?

Cipaglucosidase Alfa combined with Miglustat has been generally well tolerated in clinical trials for Pompe disease, with a safety profile similar to existing treatments like alglucosidase alfa. Over 48 months, it showed no major safety concerns, making it a potential long-term treatment option. ^{1 2 3 4 5}

What makes the drug Cipaglucosidase Alfa + Miglustat unique for treating Pompe disease?

Cipaglucosidase Alfa + Miglustat is unique because it combines a novel enzyme replacement therapy with an enzyme stabilizer, miglustat, to improve the stability and effectiveness of the treatment for Pompe disease, offering potential benefits over existing therapies like alglucosidase alfa, especially for patients who do not respond well to current treatments. ^{1 2 3 6 7}

Eligibility Criteria

This trial is for children and teens aged 0 to <18 with Infantile-Onset Pompe Disease (IOPD). Participants must have seen benefits from previous treatment without major safety issues, or be new to treatment. They should not require invasive ventilation, have certain immune responses, or conditions affecting motor function. Girls in the trial cannot be pregnant or breastfeeding.

Inclusion Criteria

I have seen improvement with cipaglucosidase alfa/miglustat treatment without major side effects.

I am under 18, have IOPD with heart issues, been on ERT for 6+ months, and my condition has worsened.

I am under 6 months old, have IOPD with heart issues, and haven't had enzyme replacement therapy.

Exclusion Criteria

Criterion: You are using invasive ventilation, have specific genetic markers, had severe reactions to certain treatments, have a history of conditions affecting movement, or are pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cipaglucosidase alfa/miglustat treatment to evaluate safety, efficacy, PK, PD, and immunogenicity

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Cipaglucosidase alfa
• Cipaglucosidase alfa (ATB200)
• Miglustat
• Miglustat (AT2221)

Trial Overview The study tests Cipaglucosidase alfa/Miglustat's safety and effectiveness in kids who've had enzyme replacement therapy (ERT) and those who haven't. It's an open-label Phase 3 trial, meaning everyone knows what treatment they're getting, focusing on how the body processes the drugs and their impact on IOPD.

Participant Groups

Group I: Cohort 2: Cipaglucosidase Alfa/Miglustat in ERT-naïve pediatric IOPD subjects Experimental Treatment 2 Interventions

Pediatric IOPD subjects \<6 months

Group II: Cohort 1: Cipaglucosidase Alfa/Miglustat in ERT-experienced pediatric IOPD subjects Experimental Treatment 2 Interventions

Pediatric IOPD subjects 6 months to \<18 years experiencing clinical decline

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]

Avalglucosidase alfa, a new enzyme replacement therapy for Pompe disease, is designed to enhance binding to the cation-independent mannose-6-phosphate receptor, which is crucial for effective treatment.

While the small molecule miglustat increased the stability of both alglucosidase alfa and avalglucosidase alfa, it did not improve their effectiveness in clearing glycogen in Pompe mice, highlighting the importance of receptor-mediated uptake for therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increasing Enzyme Mannose-6-Phosphate Levels but Not Miglustat Coadministration Enhances the Efficacy of Enzyme Replacement Therapy in Pompe Mice. Anding, A., Kinton, S., Baranowski, K., et al.[2023]

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]

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

Increasing Enzyme Mannose-6-Phosphate Levels but Not Miglustat Coadministration Enhances the Efficacy of Enzyme Replacement Therapy in Pompe Mice. [2023]