A Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease

Amicus Therapeutics

Status and phase: Completed; Phase 2

Conditions: Fabry Disease

Treatments: Drug: migalastat HCl

Study type: Interventional

Funder types: Industry

Identifiers

NCT00214500

FAB-CL-201 (AA1565520)

Details and patient eligibility

About

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

Full 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.

Enrollment: 9 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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9 participants in 1 patient group

Migalastat

Experimental group

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.

Treatment:

Drug: migalastat HCl