Clinical trial NCT01218659: Study to Compare the Efficacy and Safety of Oral AT1001 and Enzyme Replacement Therapy in Patients With Fabry Disease
Official title: A Randomized, Open-Label Study to Compare the Efficacy and Safety of AT1001 and Enzyme Replacement Therapy (ERT) in Patients With Fabry Disease and AT1001-Responsive GLA Mutations, Who Were Previously Treated With ERT
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fabry Disease
Keywords: Amicus Therapeutics
Galafold
AT1001
Migalastat
Lead sponsor: Amicus Therapeutics
Sponsor class: INDUSTRY
First posted: 2010-10-11
Enrollment: 68
Sex: ALL
Minimum age (years): 16
Maximum age (years): 74
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This was a Phase 3, randomized, open-label, active-controlled study to evaluate the efficacy and safety of 150 milligrams (mg) of migalastat hydrochloride (migalastat) (equivalent to 123 mg of migalastat) once every other day (QOD) and ERT in male and female participants with Fabry disease who were receiving ERT and who have an α Gal-A mutation that is amenable to migalastat, based on the clinical trial HEK assay. This was a 2-part study. Part 1, the 18-month randomized phase, evaluated participants who received either migalastat 150 mg QOD or ERT per prescribing physicians' instructions for efficacy and safety. Part 2, the optional 12-month open-label extension (OLE) phase in which all participants received migalastat, also explored efficacy and safety. For Part 2, all participants who received ERT in Part 1 were given migalastat. Data presented in this posting include efficacy data from the 18-month randomized period and safety data from the entire study (18-month randomized period and 12-month optional OLE \[total of 30 months\]).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Annualized Rate Of Change From Baseline To Month 18 In Measured Glomerular Filtration Rate
timeFrame: Baseline to Month 18
measure: Annualized Rate Of Change From Baseline To Month 18 In eGFR
timeFrame: Baseline to Month 18
Secondary outcomes:
measure: Annualized Rate Of Change From Baseline To Month 18 In eGFR By The Modification Of Diet In Renal Disease Equation
timeFrame: Baseline to Month 18
Other outcomes:
Locations:
city: Los Angeles
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Decatur
country: United States
state: Georgia
city: Grand Rapids
country: United States
state: Michigan
city: Portland
country: United States
state: Oregon
city: Pittsburgh
country: United States
state: Pennsylvania
city: Fairfax
country: United States
state: Virginia
city: Milwaukee
country: United States
state: Wisconsin
city: Parkville
country: Australia
state: Victoria
city: Perth
country: Australia
state: West Australia
city: Vienna
country: Austria
city: Edegem
country: Belgium
city: Sao Paulo
country: Brazil
city: Copenhagen
country: Denmark
city: Garches
country: France
city: Lille
country: France
city: Firenze
country: Italy
city: Niigata
country: Japan
city: Osaka
country: Japan
city: Osaka
country: Japan
city: Tokyo
country: Japan
city: Cambridge
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Salford
country: United Kingdom
Study officials:
affiliation: Amicus Therapeutics
name: Medical Monitor, Clinical Research
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.