Migalastat for Fabry Disease

Recruiting at 20 trial locations

Overseen By Amicus Therapeutics Patient Advocacy

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Amicus Therapeutics

Must not be taking: Miglitol, Agalsidase, Miglustat

Disqualifiers: Kidney transplant, Peritoneal dialysis, 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 8 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 12 months

14 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called migalastat to determine its safety and effectiveness for people with Fabry disease who have severe kidney problems. Fabry disease is a genetic disorder that can cause serious issues, including kidney damage. Participants will be divided into two groups: one with severe kidney impairment and another with end-stage kidney disease, where kidneys have almost stopped working. Suitable candidates include those with Fabry disease and significant kidney issues, such as individuals on regular dialysis. 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 requires that you do not take certain medications like Glyset, Replagal, Fabrazyme, or Zavesca while participating. If you are on these, you would need to stop them to join the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that migalastat is generally well tolerated by people with Fabry disease. In studies, most patients took the medication without major problems. One study found it was safe for use over a year in 50 patients.

However, migalastat might not suit individuals with very low kidney function. For those with an estimated glomerular filtration rate (a measure of kidney health) below 30, it may not be the best choice.

Overall, evidence suggests that migalastat is safe for many with Fabry disease, but those with serious kidney issues should consult their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Fabry Disease?

Researchers are excited about migalastat for Fabry disease because it works differently from the current standard treatments, which are mainly enzyme replacement therapies like agalsidase beta and agalsidase alfa. Unlike these treatments, migalastat is a pharmacological chaperone that targets the underlying genetic mutation in Fabry disease, helping to stabilize the body's own dysfunctional enzyme. This oral treatment offers a more convenient administration method compared to the regular intravenous infusions required by enzyme replacement therapies. Additionally, migalastat is tailored to treat patients with amenable mutations, potentially offering a more personalized approach to managing Fabry disease.

What evidence suggests that migalastat might be an effective treatment for Fabry disease?

Previous studies have shown that migalastat is significantly effective in treating Fabry disease, a genetic disorder caused by a deficiency of the enzyme alpha-galactosidase A. Research indicates that migalastat improves heart health by enhancing heart structure in patients. It has also proven more effective than a placebo in addressing key symptoms of Fabry disease. This treatment is particularly beneficial for patients with specific genetic types of the disease, known as amenable GLA variants. In this trial, participants with severe renal impairment or end-stage renal disease will receive migalastat, highlighting its potential effectiveness for those with severe kidney problems. ^{4 6 7 8 9}

Who Is on the Research Team?

Clinical Research

Principal Investigator

Amicus Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults with Fabry disease and severe kidney impairment, including those on stable hemodialysis. Participants must have a specific GLA gene variant treatable by migalastat and agree to use contraception if of reproductive potential. Exclusions include pregnancy, breastfeeding, unstable heart conditions, recent other investigational drugs or gene therapy, allergy to migalastat or similar drugs.

Inclusion Criteria

If of reproductive potential, both male and female patients agree to use a medically accepted method of contraception

My records show a GLA variant treatable with migalastat.

I have end-stage renal disease and will complete all my dialysis sessions as prescribed.

Exclusion Criteria

I am allergic to migalastat or similar medications.

I do not have any health conditions that would stop me from following the study's requirements.

Subject is treated or has been treated with another investigational drug (except migalastat) within the 30 days

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline

Baseline visit to confirm enrollment eligibility and conduct initial assessments

Within 30 days of screening

1 visit (in-person)

Treatment

Participants receive migalastat based on their cohort assignment and eGFRMDRD result

12 months

Regular visits as per dosing schedule

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Migalastat HCl

Trial Overview The study tests the safety and how the body processes Migalastat HCl in individuals with Fabry disease who also have severe renal impairment (SRI) or are at the end stage of renal disease (ESRD). It's an open-label study where all participants know they're receiving Migalastat.

How Is the Trial Designed?

Group I: Cohort 2: End-Stage Renal Disease Experimental Treatment 1 Intervention

All hemodialysis subjects will receive migalastat 123 mg, equivalent to 150 mg migalastat HCl (hereafter, migalastat). Subjects will take 1 migalastat capsule orally with water every other week.

Group II: Cohort 1: Severe Renal Impairment Experimental Treatment 1 Intervention

All subjects will receive migalastat 123 mg, equivalent to 150 mg migalastat HCl (hereafter, migalastat) at a dose regimen based on their eGFRMDRD result at Visit 1. Subjects will take 1 migalastat capsule orally with water either every 4 or 7 days.

Migalastat HCl is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:

Approved in European Union as Galafold for:

• Fabry disease

Approved in United States as Galafold for:

• Fabry disease

Approved in Canada as Galafold for:

• Fabry disease

Approved in Japan as Galafold for:

• Fabry disease

Approved in Switzerland as Galafold for:

• Fabry disease

Who Is Running the Clinical Trial?

Amicus Therapeutics

Lead Sponsor

Trials

55

Recruited

2,700+

Published Research Related to This Trial

In a study of 78 patients with Fabry disease treated with migalastat for at least 2 years, long-term treatment was associated with stable renal function, as indicated by minimal changes in estimated glomerular filtration rate (eGFR) regardless of whether patients were naive to enzyme replacement therapy (ERT) or had prior ERT experience.

Both ERT-naive and ERT-experienced patients showed similar annualized rates of change in eGFR, suggesting that migalastat effectively maintains renal function over time, with no significant differences based on sex or disease phenotype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of renal function in patients treated with migalastat for Fabry disease. Bichet, DG., Torra, R., Wallace, E., et al.[2023]

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]

Migalastat hydrochloride, an oral treatment for Fabry disease, was well tolerated and showed increased α-galactosidase A (α-Gal A) activity in 6 out of 9 patients, indicating its potential efficacy.

The treatment led to a reduction in globotriaosylceramide (GL-3) levels in patients with specific mutations that responded to the drug, suggesting a genotype-specific mechanism of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and pharmacodynamic effects of a pharmacological chaperone on α-galactosidase A activity and globotriaosylceramide clearance in Fabry disease: report from two phase 2 clinical studies. Germain, DP., Giugliani, R., Hughes, DA., et al.[2021]

Liposomal nystatin (Nyotran) demonstrated comparable antifungal activity to free nystatin against various fungal species, showing both fungistatic and fungicidal effects, which were similar to or lower than those of free nystatin.

While liposomal nystatin was not as effective as amphotericin B formulations, it outperformed liposomal amphotericin B, indicating that further research into liposomal nystatin's potential as an antifungal treatment is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of in vitro antifungal activities of free and liposome-encapsulated nystatin with those of four amphotericin B formulations. Johnson, EM., Ojwang, JO., Szekely, A., et al.[2020]

Migalastat is a novel oral treatment for Fabry disease that works by stabilizing mutant forms of the enzyme alpha-galactosidase A, allowing them to function better and reduce harmful substance accumulation in cells.

In pivotal Phase III studies, migalastat showed promising results, being more effective than enzyme replacement therapy in reducing left ventricular mass in patients with cardiac hypertrophy, while also demonstrating comparable effects on kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chaperone molecules: The example of Fabry disease]. Barbey, F., Monney, P., Dormond, O.[2021]

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]

Fungisome® (F), a liposomal amphotericin B product, showed significant antileishmanial activity in a murine model of cutaneous leishmaniasis, but its efficacy was lower than that of the standard treatment, AmBisome® (A).

At higher doses (15 mg/kg), Fungisome® exhibited clear signs of toxicity, indicating potential safety concerns, while AmBisome® did not show such toxicity, suggesting that Fungisome® may be less safe and effective compared to AmBisome® for treating cutaneous leishmaniasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy, toxicity and biodistribution of the liposomal amphotericin B formulations Fungisome® and AmBisome® in murine cutaneous leishmaniasis. Wijnant, GJ., Van Bocxlaer, K., Yardley, V., et al.[2021]

In a study involving 57 adults with Fabry disease, migalastat, an oral treatment, showed similar effects on renal function compared to traditional intravenous enzyme replacement therapy (ERT) over 18 months.

Migalastat treatment led to a significant reduction in left ventricular mass index, indicating potential heart health benefits, while ERT did not show this effect, suggesting migalastat may be a promising alternative for patients with amenable mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study. Hughes, DA., Nicholls, K., Shankar, SP., et al.[2022]

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]

Migalastat is an approved treatment for Fabry disease, but the effectiveness of this drug can vary based on the specific mutations present in patients, with 367 known amenable mutations and 711 non-amenable mutations.

Current in vitro assays used to determine mutation amenability may not accurately predict in vivo responses, leading to discrepancies that require physicians to closely monitor patient responses to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro and In Vivo Amenability to Migalastat in Fabry Disease. Lenders, M., Stappers, F., Brand, E.[2020]

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]

In an eight-year study involving 92 patients, intermittent high-dose liposomal Amphotericin B (L-AmB) was found to have manageable and reversible toxicity, with hypokalaemia being the most common serious side effect in 23% of treatment courses.

Breakthrough invasive fungal infections (IFI) were rare, occurring in only 1.8% of cases, suggesting that L-AmB is an effective prophylactic option for high-risk haemato-oncology patients who cannot use triazoles due to drug interactions or toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Intermittent High-Dose Liposomal Amphotericin B Antifungal Prophylaxis in Haemato-Oncology: An Eight-Year Single-Centre Experience and Review of the Literature. Youngs, J., Low, JM., Whitney, L., et al.[2021]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK533454/

Executive Summary - Pharmacoeconomic Review Report - NCBI Migalastat (Galafold) is indicated for the long-term treatment of adults with a confirmed diagnosis of Fabry disease (alpha-galactosidase A deficiency) who have ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02194985

NCT02194985 | Open-Label Extension Study of the Long- ... This is an open-label extension study intended to provide continued treatment with migalastat hydrochloride (HCl) for participants with Fabry disease who ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1096719220301761

Long-term efficacy and safety of migalastat treatment in ... These results suggest that switching to migalastat treatment from ERT can lead to sustained improvements in cardiac structure in patients with left ventricular ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6647464/

Migalastat: A Review in Fabry Disease - PMC - PubMed Central In the mITT population, migalastat was significantly more effective than placebo with regards to other efficacy endpoints, including the mean ...

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2018/208623Orig1s000OtherR.pdf

208623Orig1s000 - accessdata.fda.gov GALAFOLD (migalastat) capsules is a New Molecular Entity (NME) with a proposed indication for the treatment of adults with a confirmed diagnosis ...

6. ema.europa.eu ema.europa.eu/en/documents/product-information/galafold-epar-product-information_en.pdf

Galafold, INN-migalastat - European Medicines Agency 1-year safety data from the open label AT1001-020 ... efficacy and safety of Galafold in 50 male and female patients with Fabry disease who were naïve to.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23474038/

A Phase 2 Study of Migalastat Hydrochloride in Females ... Results: Migalastat HCl was generally well tolerated. Patients with amenable mutations seem to demonstrate greater pharmacodynamic response to migalastat HCl ...

8. medsafe.govt.nz medsafe.govt.nz/profs/datasheet/g/galafoldcap.pdf

Galafold® (MIGALASTAT) HARD CAPSULES Galafold is not recommended for use in patients with Fabry disease who have estimated. GFR less than 30 mL/min/1.73 m2 (see Section 5.2 ...

9. revistanefrologia.org revistanefrologia.org/index.php/rcn/article/view/644

Migalastat as oral monotherapy for Fabry disease Conclusions: Migalastat was generally well tolerated in both trials. Subsequent extension publications showed similar results, confirming the ...