A 12-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease

October 1, 2018 updated by: Amicus Therapeutics

A Phase 2, Open-Label, Single Dose Level, 12-Week Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of AT1001 in Patients With Fabry Disease

Study to evaluate the safety, tolerability, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) and how migalastat works in participants with Fabry disease.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This was a Phase 2, open-label study in male participants with Fabry disease. The study consisted of a 4-week screening period during which participants' genotype was assessed for α-galactosidase A (α-Gal A) activity in response to migalastat via an in vitro assay. Participants were required to have α-Gal A activity responsive to migalastat. The study consisted of a 12-week treatment period, followed by an optional 36-week extension period. Participants received migalastat 150 milligrams (mg) once every other day (QOD) for 12 weeks during the treatment period. Participants could then opt to participate in the extension period.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Males between 18 and 65 years of age (inclusive)
  • Hemizygous for Fabry disease
  • Had a confirmed diagnosis of Fabry disease with a documented missense gene mutation (individual or familial)
  • Had enhanceable enzyme activity based on in vitro tests
  • Had documented evidence of cardiac and/or renal dysfunction (for example, abnormal electrocardiogram (ECG), left ventricular hypertrophy, renal insufficiency) and/or cerebral tissue dysfunction documented by evidence of stroke and/or peripheral nervous tissue dysfunction (for example, intolerance to heat/cold, decrease of perspiration)
  • Must have been previously untreated by enzyme replacement therapy (ERT) or substrate depletion for Fabry disease or were able to stop ERT for at least 18 weeks or up to three months, and be willing to undergo two kidney and three skin biopsies
  • Agreed to be sexually abstinent or use a condom with spermicide when engaging in sexual activity during the course of the study and for a period of 30 days following their completion of the study
  • Were willing and able to sign an informed consent form

Exclusion Criteria:

  • History of significant disease other than Fabry disease
  • History of organ transplant
  • Serum creatinine >2 mg per deciliter on Day -2
  • Screening 12-lead ECG demonstrating corrected QT interval >450 milliseconds prior to dosing
  • Pacemaker or other contraindication for magnetic resonance imaging (MRI) scanning
  • Took any of the following prohibited medications: Fabrazyme® (agalsidase beta), Replagal™ (agalsidase alfa), Glyset® (miglitol), Zavesca® (miglustat), or any experimental therapy for any indication
  • Participated in a previous clinical trial in the last 30 days
  • Any other condition, which, in the opinion of the investigator, would jeopardize the safety of the participant or impact the validity of the study results

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Migalastat
Migalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week extension period.
Drug: migalastat HCl
Other Names:
  • AT1001
  • Galafold
  • migalastat

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
Time Frame: Day 1 (after dosing) through Week 48 (end of extension period)

TEAEs were defined as any adverse event with a start date on or after administration of study drug or pre-existing conditions that worsened on or after the start of the first study drug administration (on Day 1). A severe adverse event was defined as an adverse event that was incapacitating and required medical intervention. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through Week 48 is presented.

A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Day 1 (after dosing) through Week 48 (end of extension period)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 12, And Week 48
Time Frame: Baseline, Week 12 (end of treatment period), Week 48 (end of extension period)

PBMCs were isolated from whole blood and lysed, and α-Gal A activity was measured by a validated fluorometric assay, with catalysis to fluorescent 4-methylumbelliferone (4-MU) as the activity measure. The activity values obtained were normalized to protein (measured using a colorimetric assay) and reported as enzyme activity (nanomole [nmol] 4-MU/hour [hr]) per mg of protein. On Day 1 of the first visit and at every visit thereafter, the samples were collected prior to dosing with migalastat.

α-Gal A activity in PBMCs are presented by individual participants. Values of "0" presented below represent α-Gal A activity levels that were below the lower limit of quantification.
Baseline, Week 12 (end of treatment period), Week 48 (end of extension period)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amicus Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 27, 2006

Primary Completion (Actual)

May 8, 2008

Study Completion (Actual)

May 8, 2008

Study Registration Dates

First Submitted

January 27, 2006

First Submitted That Met QC Criteria

January 27, 2006

First Posted (Estimate)

January 31, 2006

Study Record Updates

Last Update Posted (Actual)

October 31, 2018

Last Update Submitted That Met QC Criteria

October 1, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FAB-CL-202 (AA1565521)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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