Study of the Effects of Oral AT1001 (Migalastat Hydrochloride) in Patients With Fabry Disease

NCT00925301 | Completed Phase 3 Results DMC

• 3 other identifiers: AT1001-011FACETS2009-013459-31
• Study Type: interventional
• Target: 67
• Locations: 13 countries
• Sites: 28

Brief Summary

The primary objective of this study was to compare the effect of migalastat (123 milligrams \[mg\] of migalastat \[equivalent to 150 mg of migalastat hydrochloride\]) (migalastat) versus placebo on kidney globotriaosylceramide (GL-3).

Conditions

Fabry Disease

Keywords

Amicus Therapeutics; AT1001; Migalastat; Pharmacokinetics; Substrate; Galafold

Outcome Measures

Primary Outcomes (1)

• Percentage Of Participants With At Least A 50% Reduction From Baseline To Month 6 In The Average Number Of Kidney Interstitial Capillary (IC) Globotriaosylceramide (GL-3) Inclusions

  Renal biopsies were taken at Baseline and Month 6 (Stage 1). The specimens were evaluated using virtual microscopy. The annotation, scoring, and adjudication of the kidney histology assessments were performed by the Clinical Pathology Endpoints Committee. The number of kidney IC GL-3 inclusions was assessed by 3 renal pathologists who were blinded to treatment assignments, participants' data, and biopsy sequence. One pathologist served as annotator and identified the 300 capillaries on up to 8 slides per specimen to be scored. Two pathologists served as scorers; these pathologists completed the blinded paired assessments. Each pathologist served as annotator/adjudicator for 1/3 of the cases. Paired assessments were undertaken at Baseline and Month 6. Assessments were made using digital images. A responder was defined as a participant with a ≥50% reduction from Baseline to Month 6 in the average number of kidney IC GL-3 inclusions.

  Baseline, Month 6

Secondary Outcomes (2)

• Percent Change In Kidney IC GL-3 Inclusions From Baseline To Month 6

  Baseline, Month 6

• Change From Baseline Through Month 24 In Urine GL-3 Levels

  Baseline, Months 6, 12, and 24

Other Outcomes (1)

• Change From Month 6 To Month 12 In Average Number Of Kidney IC GL-3 Inclusions

  Month 6, Month 12

Study Arms (2)

Migalastat

EXPERIMENTAL

Migalastat 150-mg capsule taken orally every other day (QOD) for 6 months and an open-label 6-month treatment extension, followed by an optional, 12-month, open-label treatment extension.

Drug: migalastat hydrochloride

Placebo

PLACEBO COMPARATOR

Placebo capsule taken orally QOD for 6 months.

Drug: Placebo

Interventions

migalastat hydrochloride DRUG

Oral capsule QOD

Also known as: AT1001, Galafold, Migalastat

Migalastat

Placebo DRUG

Oral capsule QOD

Placebo

Eligibility Criteria

• Age: 16 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female between the ages of 16 and 74 diagnosed with Fabry disease.
• Confirmed mutant form of α-galactosidase A shown to be responsive to migalastat in vitro.
• Participant has never been treated with enzyme replacement therapy (ERT) or has not received ERT for 6 consecutive months or longer before the screening visit for the study.
• Urine GL-3 ≥4 times the upper limit of normal at screening.
• Participants taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers must be on a stable dose for a minimum of 4 weeks before the baseline visit.
• Females who can become pregnant and all males agree to be sexually abstinent or use medically accepted methods of birth control during the study and for 30 days after study completion.
• Participant is willing and able to provide written informed consent and assent, if applicable.

You may not qualify if:

• Participant has undergone or is scheduled to undergo kidney transplantation, or is currently on dialysis.
• Estimated glomerular filtration rate \<30 milliliters per minute per 1.73 meters squared (chronic kidney disease Stage 4 or 5) based on the Modification of Diet in Renal Disease equation at screening.
• Pregnant or breast-feeding.
• History of allergy or sensitivity to study medication (including excipients) or other iminosugars (for example, miglustat, miglitol).
• Participant is treated or has been treated with any investigational drug within 30 days of study start.
• Participant is currently treated or has ever been treated with migalastat.

Sponsors & Collaborators

• Amicus Therapeutics: lead

Study Sites (28)

Unknown Facility

Los Angeles, California, 90048, United States

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San Francisco, California, 94143, United States

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Decatur, Georgia, 30033, United States

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Chicago, Illinois, 60611, United States

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Kansas City, Kansas, 66160, United States

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Boston, Massachusetts, 02114, United States

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Grand Rapids, Michigan, 49525, United States

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New York, New York, 10032, United States

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Pittsburgh, Pennsylvania, 15224, United States

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Dallas, Texas, 75226, United States

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Salt Lake City, Utah, 84132, United States

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Springfield, Virginia, 22152, United States

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Seattle, Washington, 98195, United States

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Buenos Aires, B1629ODT, Argentina

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Adelaide, 5006, Australia

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Parkville, 3050, Australia

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Porto Alegre, 90035-903, Brazil

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São Paulo, 14048-900, Brazil

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Montreal, Quebec, H4J 1C5, Canada

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Copenhagen, DK-2100, Denmark

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Cairo, 11451, Egypt

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Garches, 92380, France

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Roma, 00168, Italy

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Warsaw, 04-628, Poland

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Barcelona, 08025, Spain

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Zaragoza, 50009, Spain

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Ankara, 06500, Turkey (Türkiye)

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Salford, M6 8HD, United Kingdom

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Related Publications (5)

• Bichet DG, Aerts JM, Auray-Blais C, Maruyama H, Mehta AB, Skuban N, Krusinska E, Schiffmann R. Assessment of plasma lyso-Gb3 for clinical monitoring of treatment response in migalastat-treated patients with Fabry disease. Genet Med. 2021 Jan;23(1):192-201. doi: 10.1038/s41436-020-00968-z. Epub 2020 Sep 30.

  PMID: 32994552 DERIVED

• Germain DP, Nicholls K, Giugliani R, Bichet DG, Hughes DA, Barisoni LM, Colvin RB, Jennette JC, Skuban N, Castelli JP, Benjamin E, Barth JA, Viereck C. 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. Genet Med. 2019 Sep;21(9):1987-1997. doi: 10.1038/s41436-019-0451-z. Epub 2019 Feb 6.

  PMID: 30723321 DERIVED

• Schiffmann R, Bichet DG, Jovanovic A, Hughes DA, Giugliani R, Feldt-Rasmussen U, Shankar SP, Barisoni L, Colvin RB, Jennette JC, Holdbrook F, Mulberg A, Castelli JP, Skuban N, Barth JA, Nicholls K. Migalastat improves diarrhea in patients with Fabry disease: clinical-biomarker correlations from the phase 3 FACETS trial. Orphanet J Rare Dis. 2018 Apr 27;13(1):68. doi: 10.1186/s13023-018-0813-7.

  PMID: 29703262 DERIVED

• Benjamin ER, Della Valle MC, Wu X, Katz E, Pruthi F, Bond S, Bronfin B, Williams H, Yu J, Bichet DG, Germain DP, Giugliani R, Hughes D, Schiffmann R, Wilcox WR, Desnick RJ, Kirk J, Barth J, Barlow C, Valenzano KJ, Castelli J, Lockhart DJ. The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat. Genet Med. 2017 Apr;19(4):430-438. doi: 10.1038/gim.2016.122. Epub 2016 Sep 22.

  PMID: 27657681 DERIVED

• Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR, Feliciani C, Shankar SP, Ezgu F, Amartino H, Bratkovic D, Feldt-Rasmussen U, Nedd K, Sharaf El Din U, Lourenco CM, Banikazemi M, Charrow J, Dasouki M, Finegold D, Giraldo P, Goker-Alpan O, Longo N, Scott CR, Torra R, Tuffaha A, Jovanovic A, Waldek S, Packman S, Ludington E, Viereck C, Kirk J, Yu J, Benjamin ER, Johnson F, Lockhart DJ, Skuban N, Castelli J, Barth J, Barlow C, Schiffmann R. Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat. N Engl J Med. 2016 Aug 11;375(6):545-55. doi: 10.1056/NEJMoa1510198.

  PMID: 27509102 DERIVED

MeSH Terms

Conditions

Fabry Disease

Interventions

migalastat; larazotide acetate

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Limitations and Caveats

During Phase 3, prior to unblinding, the assay used for enrollment was validated (GLP HEK assay). Mutant forms of α-Gal A that met assay criteria were categorized as amenable; additional analyses were subsequently performed on this target population.

Results Point of Contact

• Title: Medical Affairs
• Organization: Amicus Therapeutics

MedInfoUSA@amicusrx.com

+1-877-426-4287 (877-4-AMICUS)

Study Officials

• Medical Monitor, Clinical Research

  Amicus Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Sponsor and Assessor were also blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2009
• First Posted: June 22, 2009
• Study Start: October 23, 2009
• Primary Completion: June 12, 2012
• Study Completion: January 29, 2014
• Last Updated: October 30, 2018
• Results First Posted: October 30, 2018

Record last verified: 2018-10

Locations

AR (1); AU (2); US (13); BR (2); IT (1); FR (1); DK (1); GB (1); PL (1); EG (1); TU (1); CA (1); ES (2)