NCT00283933

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

Completed Phase 2 Results posted Last updated 7 September 2018

What this trial tests

Phase 2 trial testing migalastat HCl in Fabry Disease in 5 participants. Completed in 12 March 2008.

Timeline

9 May 2006

Primary endpoint
12 March 2008

12 March 2008

Quick facts

Lead sponsor	Amicus Therapeutics
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	5
Start date	9 May 2006
Primary completion	12 March 2008
Estimated completion	12 March 2008
Sites	2 locations across France, United Kingdom

Drugs / interventions tested

• migalastat HCl — full drug profile →

Conditions studied

• Fabry Disease — all drugs for Fabry Disease →

Sponsor

Amicus Therapeutics — full company profile →

Who can join

Adults 18 to 65, male only, with Fabry Disease. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) Primary · Day 1 (after dosing) through Week 48

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.

Group	Value	95% CI
Migalastat	0

α-Galactosidase A (α-Gal A) Activity In Peripheral Blood Mononuclear Cells (PBMC) At Baseline, Week 24, And Week 48 Secondary · Baseline, Week 24 (end of treatment period), Week 48 (end of extension period)

PBMC 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/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 leukocytes are presented by individual participants.

Participant 1: Baseline

Group	Value	95% CI
Migalastat	0.05

Participant 1: Week 24

Group	Value	95% CI
Migalastat	0.36

Participant 1: Week 48

Group	Value	95% CI
Migalastat	0.1

Participant 2: Baseline

Group	Value	95% CI
Migalastat	0.06

Participant 2: Week 24

Group	Value	95% CI
Migalastat	0.13

Participant 2: Week 48

Group	Value	95% CI
Migalastat	0.1

Participant 3: Baseline

Group	Value	95% CI
Migalastat	0.14

Participant 3: Week 24

Group	Value	95% CI
Migalastat	0.3

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 after dosing through Week 48 (end of extension period). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Migalastat

Serious: 0/5 (0%)

Deaths: —

Other adverse events (18 terms — click to expand)

Reaction	System	Migalastat
Proteinuria	Renal and urinary disorders	—
Headache	Nervous system disorders	—
Ventricular tachycardia	Cardiac disorders	—
Diarrhoea	Gastrointestinal disorders	—
Gastroenteritis	Infections and infestations	—
Nasopharyngitis	Infections and infestations	—
Gamma-glutamyltransferase increased	Investigations	—
Gout	Metabolism and nutrition disorders	—
Arthralgia	Musculoskeletal and connective tissue disorders	—
Bursitis	Musculoskeletal and connective tissue disorders	—
Joint swelling	Musculoskeletal and connective tissue disorders	—
Haematuria	Renal and urinary disorders	—
Scrotal mass	Reproductive system and breast disorders	—
Pruritis	Skin and subcutaneous tissue disorders	—
Contusion	Injury, poisoning and procedural complications	—
Muscle strain	Injury, poisoning and procedural complications	—
Dizziness	Nervous system disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—

Data from ClinicalTrials.gov NCT00283933 adverse events section.

Sponsor's own description

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

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat.
   Benjamin ER, Della Valle MC, Wu X, Katz E, et al · · 2017 · cited 164× · PMID 27657681 · DOI 10.1038/gim.2016.122
2. Safety and pharmacodynamic effects of a pharmacological chaperone on α-galactosidase A activity and globotriaosylceramide clearance in Fabry disease: report from two phase 2 clinical studies.
   Germain DP, Giugliani R, Hughes DA, Mehta A, et al · · 2012 · cited 69× · PMID 23176611 · DOI 10.1186/1750-1172-7-91
3. A pharmacogenetic approach to identify mutant forms of α-galactosidase A that respond to a pharmacological chaperone for Fabry disease.
   Wu X, Katz E, Della Valle MC, Mascioli K, et al · · 2011 · cited 67× · PMID 21598360 · DOI 10.1002/humu.21530
4. Migalastat HCl reduces globotriaosylsphingosine (lyso-Gb3) in Fabry transgenic mice and in the plasma of Fabry patients.
   Young-Gqamana B, Brignol N, Chang HH, Khanna R, et al · · 2013 · cited 33× · PMID 23472096 · DOI 10.1371/journal.pone.0057631
5. Abstracts of the 26th Annual North American Cystic Fibrosis Conference. October 11-13, 2012. Orlando, Florida, USA.
   · 2012 · PMID 23002459