Back to resultsA Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease
Primary Purpose
Fabry Disease
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
migalastat HCl
Sponsored by
About this trial
This is an interventional treatment trial for Fabry Disease focused on measuring Amicus Therapeutics, AT1001, Galafold, Migalastat, Substrate
Eligibility Criteria
Inclusion Criteria: Males between 18 and 55 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 In the judgment of the investigator, were either able to safely suspend ERT throughout the study, or be ERT naive 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 completion of the study Were willing and able to sign an informed consent form Exclusion Criteria: History of significant disease other than Fabry disease (for example, end-stage renal disease; Class III or IV heart disease [per the New York Heart Association classification]; current diagnosis of cancer, except for basal cell carcinoma of the skin; diabetes [unless hemoglobin A1c ≤8]; or neurological disease that would have impaired the participant's ability to participate in the study) History of organ transplant Serum creatinine >2 mg per deciliter on Day -2 Screening 12-lead electrocardiogram demonstrating corrected QT interval >450 milliseconds prior to dosing Taking a medication prohibited by the protocol: 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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Migalastat
Arm Description
Migalastat was administered orally during the 12-week treatment period and then during the optional 2 treatment extension periods. Treatment Period: Migalastat 25 mg BID for Weeks 1 and 2 (Day 1 through the morning dose on Day 14). Migalastat 100 mg BID for Weeks 3 and 4 (Day 15 through the morning dose on Day 28). Migalastat 250 mg BID for Weeks 5 and 6 (Day 29 through the morning dose on Day 42). Migalastat 25 mg BID for Weeks 6 to 12 (Days 43 to 84). Extension Period: Migalastat 25 mg BID for Weeks 12 through 48. Migalastat 50 mg QD for Weeks 48 through 96.
Outcomes
Primary Outcome Measures
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
TEAEs were defined as any adverse event with 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 96 is presented. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Secondary Outcome Measures
PK: Area Under The Concentration Versus Time Curve (AUC) After Administration Of Migalastat
The AUC from time zero to 12 hours (hr) postdose (AUC0-12) was evaluated in plasma following a single dose of migalastat 25, 100, and 250 mg on Days 1, 15, and 29, respectively. In addition, AUC0-12 was assessed following multiple doses (14 days) of migalastat 25, 100, and 250 mg on Days 14, 28, and 42, respectively.
α-Galactosidase A (α-Gal A) Activity In Leukocytes At Baseline, Week 12, And Week 96
Leukocytes were isolated from whole blood and lysed, and α-Gal A activity was measured using 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/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 leukocytes are presented by individual participants.
Full Information
NCT ID
NCT00214500
First Posted
September 13, 2005
Last Updated
October 1, 2018
Sponsor
Amicus Therapeutics
1. Study Identification
Unique Protocol Identification Number
NCT00214500
Brief Title
A Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease
Official Title
A Phase 2, Open-Label, Multicenter, 12-Week Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AT1001 in Patients With Fabry Disease
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
January 2, 2006 (Actual)
Primary Completion Date
January 29, 2008 (Actual)
Study Completion Date
January 29, 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amicus Therapeutics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) in participants with Fabry disease.
Detailed Description
This was a Phase 2, open-label study in male participants with Fabry disease. All participants who met initial eligibility criteria underwent a 28-day screening period, including a 14-day run-in with migalastat (150 milligrams [mg] migalastat once a day [QD] from Days -28 to -15) to assess eligibility for entering the treatment period of the study. Participants who entered the treatment period were required to have α-galactosidase A (α-Gal A) activity responsive to migalastat.
Fifteen participants received at least 1 dose of study drug, however, 6 of these participants did not demonstrate α-Gal A activity responsive to migalastat and were thus screen failures (these participants are hereafter referred to as "dosed screen failures") due to not meeting all inclusion criteria for treatment. Therefore, 9 participants were enrolled into the treatment period (these participants are hereafter referred to as "eligible-enrolled").
Eligible-enrolled participants (those who satisfied the criteria for inclusion in the study) received escalating doses of migalastat twice a day (BID) for 6 weeks (Days 1 to 42), followed by 6 weeks at 1 dose level BID (Days 43 to 84) during the treatment period. Participants could then opt to participate in the extension period. The study consisted of 2 optional extension periods, the first through Week 48 and the second through Week 96. For participants who did not continue into the optional treatment extension, the study included a 2-week follow-up period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fabry Disease
Keywords
Amicus Therapeutics, AT1001, Galafold, Migalastat, Substrate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Migalastat
Arm Type
Experimental
Arm Description
Migalastat was administered orally during the 12-week treatment period and then during the optional 2 treatment extension periods.
Treatment Period:
Migalastat 25 mg BID for Weeks 1 and 2 (Day 1 through the morning dose on Day 14).
Migalastat 100 mg BID for Weeks 3 and 4 (Day 15 through the morning dose on Day 28).
Migalastat 250 mg BID for Weeks 5 and 6 (Day 29 through the morning dose on Day 42).
Migalastat 25 mg BID for Weeks 6 to 12 (Days 43 to 84).
Extension Period:
Migalastat 25 mg BID for Weeks 12 through 48.
Migalastat 50 mg QD for Weeks 48 through 96.
Intervention Type
Drug
Intervention Name(s)
migalastat HCl
Other Intervention Name(s)
AT1001, Galafold, migalastat
Primary Outcome Measure Information:
Title
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
Description
TEAEs were defined as any adverse event with 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 96 is presented. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Time Frame
Day 1 (after dosing) through Week 96
Secondary Outcome Measure Information:
Title
PK: Area Under The Concentration Versus Time Curve (AUC) After Administration Of Migalastat
Description
The AUC from time zero to 12 hours (hr) postdose (AUC0-12) was evaluated in plasma following a single dose of migalastat 25, 100, and 250 mg on Days 1, 15, and 29, respectively. In addition, AUC0-12 was assessed following multiple doses (14 days) of migalastat 25, 100, and 250 mg on Days 14, 28, and 42, respectively.
Time Frame
0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 10 hr (postdose)
Title
α-Galactosidase A (α-Gal A) Activity In Leukocytes At Baseline, Week 12, And Week 96
Description
Leukocytes were isolated from whole blood and lysed, and α-Gal A activity was measured using 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/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 leukocytes are presented by individual participants.
Time Frame
Baseline, Week 12 (end of treatment period), Week 96 (end of extension period)
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males between 18 and 55 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
In the judgment of the investigator, were either able to safely suspend ERT throughout the study, or be ERT naive
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 completion of the study
Were willing and able to sign an informed consent form
Exclusion Criteria:
History of significant disease other than Fabry disease (for example, end-stage renal disease; Class III or IV heart disease [per the New York Heart Association classification]; current diagnosis of cancer, except for basal cell carcinoma of the skin; diabetes [unless hemoglobin A1c ≤8]; or neurological disease that would have impaired the participant's ability to participate in the study)
History of organ transplant
Serum creatinine >2 mg per deciliter on Day -2
Screening 12-lead electrocardiogram demonstrating corrected QT interval >450 milliseconds prior to dosing
Taking a medication prohibited by the protocol: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor, Clinical Research
Organizational Affiliation
Amicus Therapeutics
Official's Role
Study Director
Facility Information:
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30033
Country
United States
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27657681
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.
Results Reference
derived
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A Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease
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