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

NCT00304512 | Completed Phase 2 Results DMC

• 1 other identifier: FAB-CL-204
• Study Type: interventional
• Target: 9
• Locations: 6 countries
• Sites: 6

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 (2)

• PK: Area Under The Concentration Versus Time Curve (AUC) After Administration Of Migalastat

  0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 10 hours (postdose)

• α-Gal A Activity In Leukocytes At Baseline, Week 12, And Week 48

  Baseline, Week 12 (end of treatment period), Week 48 (end of extension period)

Study Arms (3)

Migalastat Low Dose 50 mg

EXPERIMENTAL

Migalastat 50 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.

Drug: migalastat HCl

Migalastat Middle Dose 150 mg

EXPERIMENTAL

Migalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.

Drug: migalastat HCl

Migalastat High Dose 250 mg

EXPERIMENTAL

Migalastat 250 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period.

Drug: migalastat HCl

Interventions

migalastat HCl DRUG

Also known as: AT1001, Galafold, migalastat

Migalastat High Dose 250 mg; Migalastat Low Dose 50 mg; Migalastat Middle Dose 150 mg

Eligibility Criteria

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

You may qualify if:

• Females between 18 and 65 years of age (inclusive)
• Heterozygous 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
• Were naïve to enzyme replacement therapy (ERT) and other therapies, except for palliative therapies for the signs and symptoms of Fabry disease, or stopped ERT for at least 18 weeks
• Had end organ dysfunction, even minimal, demonstrated by abnormal electrocardiogram (ECG) or evidence of left ventricular hypertrophy documented by echocardiogram or by cardiac biopsy; or renal insufficiency documented by common clinical assessments such as creatinine and glomerular filtration rate or by renal biopsy; or brain tissue dysfunction as documented by evidence of stroke (clinically or imaging); or peripheral nervous tissue dysfunction documented by complaints of intolerance to heat or cold, decreased vibratory sense and proprioception, decreased ability to perspire, or acroparesthesia.
• Were willing to undergo 2 renal and 3 skin biopsies
• Agreed to be sexually abstinent or practice an effective method of contraception when engaging in sexual activity during the course of the study and for a period of 30 days following their completion of the study for women of childbearing potential.
• Were willing and able to provide written informed consent

You may not qualify if:

• Pregnant or lactating
• History of organ transplant
• 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)
• Serum creatinine \>176 micromoles/liter on Day -2
• Screening 12-lead ECG demonstrating corrected QT interval \>450 milliseconds
• Pacemaker or other contraindication for magnetic resonance imaging scanning
• 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 (6)

Unknown Facility

Decatur, Georgia, 30033, United States

Location

Unknown Facility

Parkville, Victoria, 3050, Australia

Location

Unknown Facility

Porto Alegre, RS, 90035-903, Brazil

Location

Unknown Facility

Montreal, H4J 1C5, Canada

Location

Unknown Facility

Paris, 75015, France

Location

Unknown Facility

Salford, M6 8HD, 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

• Giugliani R, Waldek S, Germain DP, Nicholls K, Bichet DG, Simosky JK, Bragat AC, Castelli JP, Benjamin ER, Boudes PF. A Phase 2 study of migalastat hydrochloride in females with Fabry disease: selection of population, safety and pharmacodynamic effects. Mol Genet Metab. 2013 May;109(1):86-92. doi: 10.1016/j.ymgme.2013.01.009. Epub 2013 Jan 26.

  PMID: 23474038 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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 17, 2006
• First Posted: March 20, 2006
• Study Start: September 7, 2006
• Primary Completion: May 9, 2008
• Study Completion: May 9, 2008
• Last Updated: October 3, 2018
• Results First Posted: September 7, 2018

Record last verified: 2018-10

Locations

US (1); FR (1); AU (1); CA (1); GB (1); BR (1)