Open-Label Phase 3 Long-Term Safety Study of Migalastat (AT1001-041)

• ClinicalTrials.gov Identifier: NCT01458119
• Recruitment Status: Terminated
• First Posted: October 24, 2011
• Results First Posted: October 2, 2018
• Last Update Posted: October 2, 2018
• Sponsor: Amicus Therapeutics
• Information provided by (Responsible Party): Amicus Therapeutics

Tracking Information

• First Submitted Date: October 20, 2011
• First Posted Date: October 24, 2011
• Results First Submitted Date: August 10, 2018
• Results First Posted Date: October 2, 2018
• Last Update Posted Date: October 2, 2018
• Actual Study Start Date: October 14, 2011
• Actual Primary Completion Date: February 17, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 1, 2018)

Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 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. ]

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered migalastat that did not necessarily have a causal relationship with the treatment. Each AE was recorded at the time of reporting; visits typically occurred every 6 months. A TEAE was defined as an AE starting on or after the first study drug administration date. Serious AEs were life-threatening or resulted in death, persistent or significant incapacitation, inpatient or prolonged hospitalization, or a congenital anomaly. The criteria for AE severity were: Mild: minimal discomfort, does not interfere with normal everyday activities; Moderate: sufficiently discomforting, interferes with normal everyday activities; Severe: prevents normal everyday activities. The number of participants experiencing TEAEs is presented for those who received migalastat treatment. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Original Primary Outcome Measures (submitted: October 20, 2011)

• Incidence of adverse events (AEs) [ Time Frame: Up to 5 years ]
  non-serious AEs, serious AEs, and possible suicidality related AEs
• Withdrawal from treatment due to AEs [ Time Frame: Up to 5 years ]
  including non-serious and serious AEs
• Change from baseline in vital signs [ Time Frame: Up to 5 years ]
  blood pressure, heart rate
• Change from baseline in laboratory parameters [ Time Frame: Up to 5 years ]
  blood chemistry, hematology, urinalysis
• Change from baseline in echocardiogram (ECG) [ Time Frame: Up to 5 years ]
  12-lead ECG
• Change from baseline in electrocardiography (ECHO) [ Time Frame: Up to 5 years ]
  ECHO ultrasound

Current Secondary Outcome Measures (submitted: October 1, 2018)

Annualized Rate Of Change In The Estimated Glomerular Filtration Rate (eGFR) [ Time Frame: Baseline, Every 6 m until the End of Study (42 m) ]

The annualized rate of change of the eGFR was assessed per participant by the slope of the simple linear regression between the observed values and the assessment times. It was calculated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (eGFR [CKD-EPI]) and the Modification of Diet in Renal Disease (MDRD) equation (eGFR [MDRD]). The equations are as follows: eGFR [MDRD] = 175 * (Serum Creatinine)^-1.154 * (Age)^-0.203 * 1.212 (if black or African American) * 0.742 (if female); eGFR [CKD-EPI] = 141 * min(serum creatinine/kappa,1)^alpha * max(serum creatinine/kappa, 1)^-1.209 * 0.993^age * 1.1018(if female) * 1.159(if black or African American), where kappa is 0.7 for females and 0.9 for males, alpha is -0.329 for females and -0.411 for males, min is minimum of serum creatinine/kappa or 1, and max is the maximum of serum creatinine/kappa or 1. The number of participants with at least a Baseline and a post-Baseline value are presented.

Original Secondary Outcome Measures (submitted: October 20, 2011)

• Estimated glomerular filtration rate [ Time Frame: Up to 5 years ]
  based on the Modification of Diet in Renal Disease equation
• Measurement of 24-hour urine [ Time Frame: Up to 5 years ]
  protein, albumin, creatinine and globotriaosylceramide (GL-3)
• Evaluation of left ventricular mass index and ejection fraction [ Time Frame: Up to 5 years ]
  as measured by echocardiography
• Evaluation of leukocyte alpha-galactosidase A (a-Gal A) activity [ Time Frame: Up to 5 years ]
  enzyme responsible for breaking down GL-3
• Evaluation of patient reported assessment of pain [ Time Frame: Up to 5 years ]
  as assessed by the Brief Pain Inventory short form
• Evaluation of patient reported Quality of Life [ Time Frame: Up to 5 years ]
  as assessed by the Short Form-36 survey

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Fabry Disease

Intervention

Drug: migalastat hydrochloride

Oral capsule QOD

Other Names:

• AT1001
• Galafold
• Migalastat

Study Arms

Experimental: Migalastat

Migalastat 150-mg capsule taken orally QOD. The median duration of exposure was 23.5 m.

Intervention: Drug: migalastat hydrochloride

• Publications *: 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 29, 2016): 85
• Original Estimated Enrollment (submitted: October 20, 2011): 100
• Actual Study Completion Date: February 17, 2016
• Actual Primary Completion Date: February 17, 2016 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Canada, Denmark, Egypt, France, Italy, Spain, Turkey, United Kingdom, United States
• Removed Location Countries: Austria, Japan

Administrative Information

• NCT Number: NCT01458119
• Other Study ID Numbers: AT1001-041; 2011-004800-40 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Amicus Therapeutics
• Original Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
• Current Study Sponsor: Amicus Therapeutics
• Original Study Sponsor: GlaxoSmithKline
• Collaborators: Not Provided

Investigators

• Study Director: Medical Monitor, Clinical Research; Amicus Therapeutics

• PRS Account: Amicus Therapeutics
• Verification Date: October 2018