A 24-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease

NCT00283933 | Completed Phase 2 Results DMC

• 1 other identifier: FAB-CL-203 (AA1565522)
• Study Type: interventional
• Target: 5
• Locations: 2 countries
• Sites: 2

Brief Summary

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

Conditions

Fabry Disease

Keywords

Amicus Therapeutics; AT1001; Galafold; Migalastat; Substrate

Outcome Measures

Primary Outcomes (1)

• 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 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

Secondary Outcomes (1)

• α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48

  Baseline, Week 24 (end of treatment period), Week 48 (end of extension period)

Study Arms (1)

Migalastat

EXPERIMENTAL

Migalastat 150 milligrams (mg) was administered orally QOD during the 24-week treatment period and then during the optional 24-week extension period.

Drug: migalastat HCl

Interventions

migalastat HCl DRUG

Also known as: AT1001, Galafold, migalastat

Migalastat

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Were previously untreated by enzyme replacement therapy (ERT) or substrate depletion for Fabry disease, or if ERT or other specific treatment for Fabry disease was administered, were able to stop ERT for at least 30 weeks.
• Were willing to undergo 2 kidney and 3 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 completion of the study
• Were willing and able to sign an informed consent form

You may not qualify if:

• 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 \>176 millimole per deciliter on Day -2
• Screening 12-lead ECG 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

Sponsors & Collaborators

• Amicus Therapeutics: lead

Study Sites (2)

Unknown Facility

Paris, 75015, France

Location

Unknown Facility

London, NW3 2QG, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 27657681 DERIVED

• Germain DP, Giugliani R, Hughes DA, Mehta A, Nicholls K, Barisoni L, Jennette CJ, Bragat A, Castelli J, Sitaraman S, Lockhart DJ, Boudes PF. Safety and pharmacodynamic effects of a pharmacological chaperone on alpha-galactosidase A activity and globotriaosylceramide clearance in Fabry disease: report from two phase 2 clinical studies. Orphanet J Rare Dis. 2012 Nov 24;7:91. doi: 10.1186/1750-1172-7-91.

  PMID: 23176611 DERIVED

MeSH Terms

Conditions

Fabry Disease

Interventions

migalastat; larazotide acetate

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Results Point of Contact

• Title: Amicus Therapeutics
• Organization: Medical Affairs

MedInfoUSA@amicusrx.com

+1-877-426-4287 (877-4-AMICUS)

Study Officials

• Medical Monitor, Clinical Research

  Amicus Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2006
• First Posted: January 31, 2006
• Study Start: May 9, 2006
• Primary Completion: March 12, 2008
• Study Completion: March 12, 2008
• Last Updated: September 7, 2018
• Results First Posted: September 7, 2018

Record last verified: 2018-08

Locations

GB (1); FR (1)