Cipaglucosidase Alfa + Miglustat for Pompe Disease

(ROSSELLA Trial)

Recruiting at 19 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination of cipaglucosidase alfa (an enzyme replacement therapy) and miglustat for children with Pompe disease, particularly those with muscle and heart issues. The trial aims to assess the safety and effectiveness of the treatment for children who have previously tried enzyme replacement therapy (ERT) and those who have not. Eligible participants include children diagnosed with Pompe disease and heart problems, whether they have not tried ERT before or have experienced a decline despite current treatment. As a Phase 3 trial, this study serves as the final step before FDA approval, offering participants the opportunity to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of cipaglucosidase alfa and miglustat has been studied for safety in treating Pompe disease. Some patients may experience serious side effects, such as strong allergic reactions, which can be severe and potentially life-threatening.

One study found that after 104 weeks of treatment, patients generally maintained improvements or stayed stable in their condition. This suggests the treatment is well-tolerated over a long period, as many people do not experience side effects severe enough to stop the treatment.

This treatment is already approved for other uses, which provides some confidence in its safety. However, discussing any concerns with healthcare providers is important to understand what these findings might mean for individual patients. ^{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 because it offers a new approach to treating Pompe disease, especially in pediatric patients. Unlike traditional enzyme replacement therapies (ERT) that primarily focus on supplementing the missing enzyme, this combination therapy potentially enhances the enzyme's effectiveness by inhibiting the breakdown of glycogen through Miglustat. This dual action not only targets the root cause of Pompe disease more comprehensively but also holds promise for improved clinical outcomes in both ERT-experienced and ERT-naïve young patients.

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 can help treat Pompe disease, a rare genetic disorder. Participants in this trial will receive this combination therapy. In a previous study, patients who had previously received enzyme replacement therapy walked an average of 17 meters farther after 52 weeks of using these drugs, indicating improved muscle function. The treatment helps lysosomes, parts of cells that break down waste, function normally. This process helps lessen the effects of Pompe disease on the body. These drugs are already used to treat adults with late-onset Pompe disease and have proven effective in managing symptoms. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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, 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]

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]

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 (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]

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. 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.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12398902/

Cipaglucosidase alfa and miglustat for treatment of late- ... STIG study: real-world data of long-term outcomes of adults with Pompe disease under enzyme replacement therapy with alglucosidase alfa. J ...

4. pombilitiopfoldahcp.com pombilitiopfoldahcp.com/

POMBILITI® (cipaglucosidase alfa-atga) + OPFOLDA ... POMBILITI (cipaglucosidase alfa-atga) in combination with OPFOLDA (miglustat) is indicated for the treatment of adult patients with late-onset Pompe disease.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38057636/

an open-label phase I/II study (ATB200-02) - PubMed Cipaglucosidase alfa plus miglustat (cipa + mig) is a novel, two-component therapy for Pompe disease. We report data from the Phase I/II ATB200-02 study for up ...

6. pombilitiopfolda.com pombilitiopfolda.com/

Learn About POMBILITI® (cipaglucosidase alfa-atga) + ... POMBILITI in combination with OPFOLDA may cause serious side effects, including: Hypersensitivity reactions (including anaphylaxis): Severe and potentially ...

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 ...