Migalastat for Fabry Disease

Overseen By Amicus Therapeutics Patient Advocacy

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Amicus Therapeutics

Must not be taking: Miglitol, Miglustat

Disqualifiers: Renal impairment, Kidney disease, 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

8 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial requires that you have not received enzyme replacement therapy (ERT) for at least 14 days before the screening visit. Additionally, you cannot take Glyset (miglitol) or Zavesca (miglustat) within 6 months before the screening or during the study. Other medications are not specifically mentioned, so it's best to discuss with the study team.

What data supports the effectiveness of the drug migalastat for Fabry disease?

Research shows that migalastat helps maintain kidney function and reduce heart size in patients with Fabry disease who have specific genetic mutations. It is an important treatment option because it is taken orally and has shown to be generally well tolerated. ^{1 2 3 4 5}

Is migalastat safe for humans?

Migalastat has been generally well tolerated in clinical trials for Fabry disease, with studies showing it maintains kidney function and reduces heart mass. It is an oral treatment option with a good safety profile compared to enzyme replacement therapies. ^{1 2 3 4 5}

How is the drug migalastat unique in treating Fabry disease?

Migalastat is unique because it is an oral medication that acts as a pharmacological chaperone, helping to stabilize and increase the activity of specific mutant forms of the enzyme α-galactosidase A in patients with amenable mutations, unlike traditional enzyme replacement therapies that require intravenous infusions. ^{1 2 3 4 5}

What is the purpose of this trial?

An open-label study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of migalastat treatment in pediatric subjects 2 to \< 12 years of age with Fabry disease and with amenable GLA variants.

Eligibility Criteria

This trial is for children aged 2 to less than 12 with Fabry disease and specific GLA variants. They must have had a complication from the disease, not received enzyme replacement therapy in the last 14 days, and agree to use contraception if applicable. Those with severe illnesses, advanced kidney issues requiring dialysis or transplant, recent experimental treatments, or allergies to migalastat are excluded.

Inclusion Criteria

I have experienced at least one symptom or lab result indicating Fabry disease.

I am diagnosed with Fabry disease and am between 2 and less than 12 years old.

Subject's parent or legally authorized representative is willing and able to provide written informed consent and authorization for use and disclosure of personal health information or research-related health information, and subject provides assent if applicable

Exclusion Criteria

Has any intercurrent illness or condition at Visit 1 (screening) or Visit 2 (baseline) that may preclude the subject from fulfilling the protocol requirements or suggests to the investigator that the potential subject may have an unacceptable risk by participating in this study

I have taken Glyset or Zavesca in the last 6 months or will continue to take it during the study.

I need dialysis or a kidney transplant due to advanced kidney disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Stage 1

Participants receive migalastat treatment for 3 months

12 weeks

Regular visits for PK sampling and monitoring

Treatment Stage 2

Continuation of migalastat treatment for an additional 9 months

9 months

Regular visits for PK sampling and monitoring

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Migalastat

Trial Overview The study tests Migalastat HCl (20 mg) in young patients with Fabry disease. It's an open-label trial assessing safety and how well the drug works (pharmacokinetics/pharmacodynamics), as well as its effectiveness in treating symptoms related to amenable GLA variants.

Participant Groups

Group I: Migalastat HCl 20 mg Dispersible Tablets Experimental Treatment 1 Intervention

Migalastat will be administered every other day (QOD). The initial dose will be based on body weight at baseline.

Who Is Running the Clinical Trial?

Amicus Therapeutics

Lead Sponsor

Trials

55

Recruited

2,700+

Findings from Research

Migalastat (Galafold™) is the first approved oral pharmacological chaperone for treating Fabry disease in patients with specific GLA mutations, showing significant efficacy in reducing kidney globotriaosylceramide (GL-3) inclusions and plasma lyso-globotriaosylsphingosine levels after 6 months in amenable patients.

In trials, migalastat maintained renal function and reduced cardiac mass over 18 months compared to enzyme replacement therapy (ERT), demonstrating its potential as a well-tolerated treatment option for Fabry disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Migalastat: A Review in Fabry Disease. McCafferty, EH., Scott, LJ.[2020]

Migalastat (Galafold®) is an effective oral treatment for Fabry disease that can improve enzyme activity in patients with specific mutations, showing benefits such as reduced left ventricular mass and stabilized kidney function.

Switching from traditional enzyme replacement therapy to migalastat has been shown to be safe and effective, with positive outcomes observed in both treatment-naive patients and those previously on enzyme replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fabry Disease: Switch from Enzyme Replacement Therapy to Oral Chaperone Migalastat: What Do We Know Today? Perretta, F., Jaurretche, S.[2023]

In the phase 3 FACETS trial, migalastat showed clinical benefits in patients with Fabry disease, particularly in those with the classic phenotype, where significant improvements were observed in kidney function and other health markers after 24 months.

Patients with the classic phenotype experienced a decrease in harmful globotriaosylceramide inclusions and improvements in left ventricular mass and gastrointestinal symptoms, indicating that migalastat is effective regardless of the severity of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: data from the phase 3 randomized, multicenter, double-blind clinical trial and extension study. Germain, DP., Nicholls, K., Giugliani, R., et al.[2022]

Migalastat (Galafold™) has been approved in the EU for treating Fabry disease in patients with specific mutations that allow the drug to restore α-galactosidase activity.

Fabry disease is caused by a deficiency of α-galactosidase, leading to harmful accumulation of certain substances in cells, and migalastat offers a targeted treatment option for this rare disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Migalastat: First Global Approval. Markham, A.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

The GALA project: practical recommendations for the use of migalastat in clinical practice on the basis of a structured survey among Italian experts. [2021]

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

Migalastat: A Review in Fabry Disease. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Fabry Disease: Switch from Enzyme Replacement Therapy to Oral Chaperone Migalastat: What Do We Know Today? [2023]

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

Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: data from the phase 3 randomized, multicenter, double-blind clinical trial and extension study. [2022]

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

Migalastat: First Global Approval. [2018]