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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01218659




Registration number
NCT01218659
Ethics application status
Date submitted
6/10/2010
Date registered
11/10/2010
Date last updated
1/11/2018

Titles & IDs
Public title
Study to Compare the Efficacy and Safety of Oral AT1001 and Enzyme Replacement Therapy in Patients With Fabry Disease
Scientific 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
Secondary ID [1] 0 0
ATTRACT
Secondary ID [2] 0 0
AT1001-012
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fabry Disease 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - migalastat hydrochloride
Treatment: Other - agalsidase

Experimental: Migalastat - 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.

Active comparator: ERT - 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.


Treatment: Drugs: migalastat hydrochloride
150-mg capsule administered orally QOD

Treatment: Other: agalsidase
Agalsidase via intravenous infusion as prescribed by the participant's treating physician and in accordance with the approved prescribing information
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Annualized Rate Of Change From Baseline To Month 18 In Measured Glomerular Filtration Rate
Timepoint [1] 0 0
Baseline to Month 18
Primary outcome [2] 0 0
Annualized Rate Of Change From Baseline To Month 18 In eGFR
Timepoint [2] 0 0
Baseline to Month 18
Secondary outcome [1] 0 0
Annualized Rate Of Change From Baseline To Month 18 In eGFR By The Modification Of Diet In Renal Disease Equation
Timepoint [1] 0 0
Baseline to Month 18

Eligibility
Key inclusion criteria
* Male or female between the ages of 16 and 74 diagnosed with Fabry disease
* Confirmed a 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
Minimum age
16 Years
Maximum age
74 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/09/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/05/2015
Sample size
Target
Accrual to date
Final
68
Recruitment in Australia
Recruitment state(s)
VIC,West Australi
Recruitment hospital [1] 0 0
- Parkville
Recruitment hospital [2] 0 0
- Perth
Recruitment postcode(s) [1] 0 0
03050 - Parkville
Recruitment postcode(s) [2] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Oregon
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Virginia
Country [8] 0 0
United States of America
State/province [8] 0 0
Wisconsin
Country [9] 0 0
Austria
State/province [9] 0 0
Vienna
Country [10] 0 0
Belgium
State/province [10] 0 0
Edegem
Country [11] 0 0
Brazil
State/province [11] 0 0
Sao Paulo
Country [12] 0 0
Denmark
State/province [12] 0 0
Copenhagen
Country [13] 0 0
France
State/province [13] 0 0
Garches
Country [14] 0 0
France
State/province [14] 0 0
Lille
Country [15] 0 0
Italy
State/province [15] 0 0
Firenze
Country [16] 0 0
Japan
State/province [16] 0 0
Niigata
Country [17] 0 0
Japan
State/province [17] 0 0
Osaka
Country [18] 0 0
Japan
State/province [18] 0 0
Tokyo
Country [19] 0 0
United Kingdom
State/province [19] 0 0
Cambridge
Country [20] 0 0
United Kingdom
State/province [20] 0 0
London
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amicus Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
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 (a Gal-A) mutation that is amenable to migalastat, based on the clinical trial human embryonic kidney cell (HEK) assay.
Trial website
https://clinicaltrials.gov/study/NCT01218659
Trial related presentations / publications
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.
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. Erratum In: Genet Med. 2021 Jan;23(1):238. doi: 10.1038/s41436-020-01041-5.
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.
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.
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. Erratum In: J Med Genet. 2018 Jun;55(6):422-429. doi: 10.1136/jmedgenet-2016-104178corr1.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Monitor, Clinical Research
Address 0 0
Amicus Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01218659