Clinical trial NCT01458119: Open-Label Phase 3 Long-Term Safety Study of Migalastat
Official title: An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Migalastat Hydrochloride Monotherapy in Subjects With Fabry Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Fabry Disease
Keywords: Amicus Therapeutics
AT1001
Galafold
Migalastat
Lead sponsor: Amicus Therapeutics
Sponsor class: INDUSTRY
First posted: 2011-10-24
Enrollment: 85
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This was a long-term, open-label study of migalastat (123 milligrams \[mg\] of migalastat \[equivalent to 150 mg of migalastat hydrochloride\]) (migalastat) in participants with Fabry disease who completed treatment in a previous monotherapy trial with migalastat.

Detailed description: Study AT1001-041 was an open-label, noncomparative, multicenter, long-term extension study for participants with Fabry disease who completed treatment in one of three previous trials of migalastat (AT1001-011 \[NCT00925301\], AT1001-012 \[NCT01218659\], or FAB-CL-205 \[NCT00526071\]). In these trials, migalastat was given as monotherapy. This was an extension study designed to evaluate the long-term safety and efficacy of migalastat for the treatment of Fabry disease. Study visits occurred every 6 months (m). Visit evaluations included physical examinations, clinical laboratory parameters, adverse events, and participant reported outcomes.

The study consisted of a Baseline Visit, which was performed at the time of the final visit of the previous study, followed by clinic visits every 6 m for each year of the study. Study assessments included a physical examination, echocardiography, laboratory parameters, and participant-reported outcomes. Since participants enrolled in the study at varying time points based on the completion of the preceding migalastat study, treatment duration varied among participants. No maximum treatment duration was defined. There were no control groups in this study; all participants received migalastat as a 150-mg capsule taken orally once every other day (QOD) and inactive reminder capsules on alternate days.

The sponsor (Amicus Therapeutics) discontinued Study AT1001-041 for logistical reasons and not due to either safety concerns or lack of efficacy. For participants who were ongoing in Study AT1001-041 at the time of discontinuation, the investigators were offered participation in a similar open-label, long-term migalastat treatment study (AT1001-042 \[NCT02194985\]) for participants ongoing at discontinuation.

Eligibility criteria: Inclusion Criteria:

* Completed migalastat treatment in a previous Fabry disease protocol
* Both male and female participants were enrolled
* Age 16 years or older
* Male and female participants had to agree to use protocol-identified acceptable contraception

Exclusion Criteria:

* Estimated glomerular filtration rate (eGFR) in the previous study was \<30 milliliters/minute/1.73 square meters (mL/min/1.73 m\^2) unless there was a measured GFR available within 3 m of the Baseline Visit that was \>30 mL/min/1.73 m\^2
* Had undergone, or was scheduled to undergo, kidney transplantation or was currently on dialysis
* Pregnant or breast feeding
* Treated with another investigational drug (except migalastat) within 30 days of study start
* Unable to comply with study requirements, or deemed otherwise unsuitable for study entry, in the opinion of the investigator
* Had documented transient ischemic attack, stroke, unstable angina, or myocardial infarction within the 12 m before the Baseline Visit
* Had clinically significant, unstable cardiac disease in the opinion of the investigator
* Had a history of allergy or sensitivity to migalastat (including excipients) or to other iminosugars
* Required treatment with Glyset (miglitol) or Zavesca (miglustat)
* Had any intercurrent illness or condition that may have precluded the participant from fulfilling the protocol requirements
* Had a severe or unsuitable concomitant medical condition
* Had a clinically significant abnormal laboratory value and a clinically significant electrocardiogram finding at the Baseline Visit.

Primary outcomes:
measure: Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline to End of Follow-up (30 days after the end of this 42-month study), with AE reporting occurring at each study visit, which occurred once every 6 months.
Secondary outcomes:
measure: Annualized Rate Of Change In The Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline, Every 6 m until the End of Study (42 m)
Other outcomes:
Locations:
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Kansas City
country: United States
state: Kansas
city: Boston
country: United States
state: Massachusetts
city: Grand Rapids
country: United States
state: Michigan
city: New York
country: United States
state: New York
city: Portland
country: United States
state: Oregon
city: Pittsburgh
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
city: Fairfax
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Pilar
country: Argentina
city: Adelaide
country: Australia
city: Parkville
country: Australia
city: Edegem
country: Belgium
city: Porto Alegre
country: Brazil
city: Montreal
country: Canada
city: Copenhagen
country: Denmark
city: Cairo
country: Egypt
city: Garches
country: France
city: Roma
country: Italy
city: Barcelona
country: Spain
city: Ankara
country: Turkey
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: 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.