Study to Compare the Efficacy and Safety of Oral AT1001 and Enzyme Replacement Therapy in Patients With Fabry Disease

NCT01218659 | Completed Phase 3 Results DMC

• 3 other identifiers: AT1001-012ATTRACT2010-022636-37
• Study Type: interventional
• Target: 68
• Locations: 9 countries
• Sites: 24

Brief Summary

Study to compare the efficacy and safety of migalastat and enzyme replacement therapy (ERT) in male and female participants with Fabry disease who are currently receiving ERT and who have an alpha galactosidase-A (α Gal-A) mutation that is amenable to migalastat, based on the clinical trial human embryonic kidney cell (HEK) assay.

Conditions

Fabry Disease

Keywords

Amicus Therapeutics; Galafold; AT1001; Migalastat

Outcome Measures

Primary Outcomes (2)

• Annualized Rate Of Change From Baseline To Month 18 In Measured Glomerular Filtration Rate

  To assess renal function, measured glomerular filtration rate (GFR) was measured by the plasma clearance of unlabeled iohexol (mGFR-iohexol), a non-ionic contrast agent. The annualized rate of change in mGFR-iohexol from Baseline to Month 18 was analyzed using an analysis of covariance (ANCOVA) model with the following factors as covariates: treatment group, sex, age, Baseline GFR (mGFR-iohexol), and Baseline 24-hour (hr) urine protein. A threshold of \<2.2 milliliter (mL)/minute (min)/1.73 meter squared (m\^2)/year was established to compare migalastat to ERT. This difference of 2.2 mL/min/1.73 m2/year is based on the smallest expected rate of decline in estimated glomerular filtration rate (eGFR) for participants treated with agalsidase alfa for 18 months.

  Baseline to Month 18

• Annualized Rate Of Change From Baseline To Month 18 In eGFR

  The eGFR assessed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was calculated using the following: eGFR-CKD-EPI = 141 x min (Serum Creatinine/κ,1)\^(α) x max(Serum Creatinine/κ,1)\^(-1.209) x 0.993\^(Age) x 1.1018 (if female) x 1.159 (if African American or black) where: κ is 0.7 for females and 0.9 for males; α is -0.329 for females and -0.411 for males; min indicates the minimum of Serum Creatinine/κ or 1; max indicates the maximum of Serum Creatinine/κ or 1. The annualized rate of change in eGFR-CKD-EPI from Baseline to Month 18 was analyzed using an ANCOVA model with the following factors as covariates: treatment group, sex, age, Baseline GFR (eGFR-CKD-EPI), and Baseline 24-hr urine protein. A threshold of \<2.2 mL/min/1.73m\^2/year was established to compare migalastat to ERT. This difference of 2.2 mL/min/1.73 m2/year is based on the smallest expected rate of decline in eGFR for participants treated with agalsidase alfa for 18 months.

  Baseline to Month 18

Secondary Outcomes (1)

• Annualized Rate Of Change From Baseline To Month 18 In eGFR By The Modification Of Diet In Renal Disease Equation

  Baseline to Month 18

Study Arms (2)

Migalastat

EXPERIMENTAL

Participants received 150 mg migalastat orally QOD during the 18-month randomized treatment period and the optional 12-month OLE period. Participants received an inactive reminder capsule on alternate days during both treatment periods.

Drug: migalastat hydrochloride

ERT

ACTIVE COMPARATOR

Participants received ERT (either agalsidase alfa or agalsidase beta) as prescribed by the participant's treating physician and administered in accordance with the approved prescribing information during the 18-month randomized treatment period. Participants were required to be given \>80% of the currently labeled dose and regimen during the 18-month randomized treatment period. During the optional 12-month OLE period, participants received 150 mg migalastat orally QOD. Participants received an inactive reminder capsule on alternate days during the OLE.

Biological: agalsidase

Interventions

migalastat hydrochloride DRUG

150-mg capsule administered orally QOD

Also known as: AT1001, Migalastat, Galafold

Migalastat

agalsidase BIOLOGICAL

Agalsidase via intravenous infusion as prescribed by the participant's treating physician and in accordance with the approved prescribing information

Also known as: agalsidase beta; Fabrazyme, agalsidase alfa; Replagal

ERT

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 α Gal-A mutation that is amenable to migalastat, based on the clinical trial HEK assay
• Participant has been on ERT for at least 12 months before screening/baseline
• Dose level and regimen of ERT have been stable for 3 months before screening/baseline and is at least 80% of the currently labeled dose and regimen for this time period
• Glomerular filtration rate (GFR) ≥ 30 milliliter (mL)/minute (min) /1.73 m\^2
• Participants taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers must be on a stable dose for at least 4 weeks before screening/baseline
• Women who can become pregnant and all men agree to be sexually abstinent or use medically accepted methods of birth control throughout the duration of the study and for up to 30 days after last dose of study medication
• 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 any other solid organ transplantation
• Participant is on regular dialysis that is specifically for the treatment of chronic kidney disease
• Participant has had a documented transient ischemic attack, stroke, unstable angina, or myocardial infarction within the 3 months before screening/baseline
• Participant has clinically significant unstable cardiac disease in the opinion of the investigator (for example, cardiac disease requiring active management, such as symptomatic arrhythmia, unstable angina, or New York Heart Association (NYHA) class III or IV congestive heart failure)
• Pregnant or breast-feeding
• History of allergy or sensitivity to study medication (including excipients) or other iminosugars (for example, miglustat, miglitol)
• Participant has absolute contraindication to iohexol and/or inability to undergo iohexol GFR testing
• Participant requires treatment with Glyset® (miglitol), or Zavesca® (miglustat)
• Participant received any investigational/experimental drug, biologic or device within 30 days of screening/baseline
• Any intercurrent illness or condition that may preclude the participant from fulfilling the study requirements or suggests to the investigator that the participant may have an unacceptable risk by participating in this study

Sponsors & Collaborators

• Amicus Therapeutics: lead

Study Sites (25)

Unknown Facility

Los Angeles, California, 90048, United States

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Aurora, Colorado, 80045, United States

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Decatur, Georgia, 30033, United States

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Grand Rapids, Michigan, 49525, United States

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Portland, Oregon, 97239, United States

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Pittsburgh, Pennsylvania, 15224, United States

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Fairfax, Virginia, 22030, United States

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Milwaukee, Wisconsin, 53226, United States

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Parkville, Victoria, 03050, Australia

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Perth, Western Australia, 6000, Australia

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Vienna, 1090, Austria

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Edegem, 2650, Belgium

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São Paulo, 14048-900, Brazil

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Copenhagen, 2100, Denmark

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Garches, 92380, France

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Lille, 59037, France

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Florence, 50129, Italy

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Niigata, 951-8520, Japan

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Osaka, 545-8586, Japan

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Osaka, 565-0871, Japan

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Tokyo, 105-8471, Japan

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Cambridge, CB2 0QQ, United Kingdom

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London, NW3 2QG, United Kingdom

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London, WC1N 3BG, United Kingdom

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Salford, M6 8HD, United Kingdom

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Related Publications (6)

• Feldt-Rasmussen U, Hughes D, Sunder-Plassmann G, Shankar S, Nedd K, Olivotto I, Ortiz D, Ohashi T, Hamazaki T, Skuban N, Yu J, Barth JA, Nicholls K. Long-term efficacy and safety of migalastat treatment in Fabry disease: 30-month results from the open-label extension of the randomized, phase 3 ATTRACT study. Mol Genet Metab. 2020 Sep-Oct;131(1-2):219-228. doi: 10.1016/j.ymgme.2020.07.007. Epub 2020 Aug 15.

  PMID: 33012654 DERIVED

• 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

• Haninger-Vacariu N, El-Hadi S, Pauler U, Foretnik M, Kain R, Prohaszka Z, Schmidt A, Skuban N, Barth JA, Sunder-Plassmann G. Pregnancy Outcome after Exposure to Migalastat for Fabry Disease: A Clinical Report. Case Rep Obstet Gynecol. 2019 Dec 21;2019:1030259. doi: 10.1155/2019/1030259. eCollection 2019.

  PMID: 31934472 DERIVED

• Narita I, Ohashi T, Sakai N, Hamazaki T, Skuban N, Castelli JP, Lagast H, Barth JA. Efficacy and safety of migalastat in a Japanese population: a subgroup analysis of the ATTRACT study. Clin Exp Nephrol. 2020 Feb;24(2):157-166. doi: 10.1007/s10157-019-01810-w. Epub 2019 Dec 30.

  PMID: 31889231 DERIVED

• Hughes DA, Nicholls K, Shankar SP, Sunder-Plassmann G, Koeller D, Nedd K, Vockley G, Hamazaki T, Lachmann R, Ohashi T, Olivotto I, Sakai N, Deegan P, Dimmock D, Eyskens F, Germain DP, Goker-Alpan O, Hachulla E, Jovanovic A, Lourenco CM, Narita I, Thomas M, Wilcox WR, Bichet DG, Schiffmann R, Ludington E, Viereck C, Kirk J, Yu J, Johnson F, Boudes P, Benjamin ER, Lockhart DJ, Barlow C, Skuban N, Castelli JP, Barth J, Feldt-Rasmussen U. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study. J Med Genet. 2017 Apr;54(4):288-296. doi: 10.1136/jmedgenet-2016-104178. Epub 2016 Nov 10.

  PMID: 27834756 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

MeSH Terms

Conditions

Fabry Disease

Interventions

migalastat; larazotide acetate; agalsidase beta; agalsidase alfa

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

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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2010
• First Posted: October 11, 2010
• Study Start: September 8, 2011
• Primary Completion: May 27, 2014
• Study Completion: May 28, 2015
• Last Updated: November 1, 2018
• Results First Posted: November 1, 2018

Record last verified: 2018-10

Locations

BR (1); DK (1); BE (1); AU (2); FR (2); US (8); IT (1); JP (4); GB (4)