Study of the Effects of Oral AT1001 (Migalastat Hydrochloride) in Patients With Fabry Disease

• ClinicalTrials.gov Identifier: NCT00925301
• Recruitment Status: Completed
• First Posted: June 22, 2009
• Results First Posted: October 30, 2018
• Last Update Posted: October 30, 2018
• Sponsor: Amicus Therapeutics
• Information provided by (Responsible Party): Amicus Therapeutics

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Fabry Disease
• Interventions: Drug: migalastat hydrochloride; Drug: Placebo
• Enrollment: 67

Participant Flow

Recruitment Details
Pre-assignment Details	During Stage 1 (0-6 Months), all participants were randomized to either Migalastat or Placebo. After Stage 1, all participants progressed to Stage 2 where they received open-label migalastat for 6 months (>6-12 Months). After Stage 2, participants were eligible to enter the optional, 12-month, open-label extension (OLE) (>12-24 Months).

Arm/Group Title	Migalastat (0-6 Months)	Placebo (0-6 Months)	Migalastat (>6-12 Months)	Migalastat (>12-24 Months)
Arm/Group Description	Migalastat hydrochloride (migalastat) 150-milligram (mg) capsule (equivalent to 123 mg of migalastat) given orally every other day (QOD) during the 6-month, double-blind, randomized placebo-controlled treatment period (Stage 1). After Stage 1, participants progressed to Stage 2 where they received open-label migalastat for 6 months.	Placebo capsule given orally QOD during the 6-month, double-blind, randomized placebo-controlled treatment period (Stage 1). After Stage 1, participants progressed to Stage 2 where they received open-label migalastat for 6 months.	Migalastat 150-mg capsule given orally QOD during the 6-month open-label treatment period (Stage 2). Includes all participants who progressed from both the migalastat (0-6 Months) and the placebo (0-6 Months) Stage 1 treatment groups. After Stage 2, participants were eligible to enter the optional, 12-month OLE.	Migalastat 150-mg capsule given orally QOD for up to 12 months during the optional OLE. Includes all participants who decided to continue treatment after completing the 6-month, open-label Stage 2 treatment period.
Period Title: 6-Month Double-blind (Stage 1)
Started	34	33	0 [1]	0 [2]
Received at Least 1 Dose of Study Drug	34	33	0	0
Intent-to-Treat (ITT) [3]	34	33	0	0
Modified Intent-to-Treat (mITT) [4]	30	30	0	0
Completed	34	30	0	0
Not Completed	0	3	0	0
Reason Not Completed
Withdrawal by Subject	0	2	0	0
Pregnancy	0	1	0	0
[1] Zero participants noted because participants did not start Stage 2 yet.; [2] Zero participants noted because participants did not start the OLE yet.; [3] All randomized participants regardless of their participation in the study beyond Randomization.; [4] Participants with Baseline and Month 6 biopsy results.
Period Title: 6-Month Open-label (Stage 2)
Started	0 [1]	0 [1]	63 [2]	0 [3]
ITT-amenable [4]	0	0	47	0
Completed	0	0	60	0
Not Completed	0	0	3	0
Reason Not Completed
Withdrawal by Subject	0	0	1	0
Adverse Event	0	0	2	0
[1] Zero participants noted because participants had completed Stage 1.; [2] One participant (Migalastat [0-6 Months]) withdrew consent after completing Month 6.; [3] Zero participants noted because participants did not start the OLE yet.; [4] Amenable mutations based on Good Laboratory Practice (GLP) Human Embryonic Kidney (HEK) assay.
Period Title: 12-Month Open-label Extension (Optional)
Started	0 [1]	0 [1]	0 [2]	57 [3]
ITT-amenable [4]	0	0	0	42
Completed	0	0	0	54
Not Completed	0	0	0	3
Reason Not Completed
Withdrawal by Subject	0	0	0	1
Pregnancy	0	0	0	1
Lost to Follow-up	0	0	0	1
[1] Zero participants noted because participants had completed Stage 1.; [2] Zero participants noted because participants had completed Stage 2.; [3] The OLE was optional for those who completed Stage 2. Reasons for not entering were not recorded.; [4] Amenable mutations based on GLP HEK assay.

Baseline Characteristics

Arm/Group Title		Migalastat-Migalastat	Placebo-Migalastat	Total
Arm/Group Description		Migalastat 150-mg capsule given orally QOD during the 6-month, double-blind, randomized placebo-controlled treatment period (Stage 1), during the 6-month open-label treatment period (Stage 2), and for up to 12 months during the OLE.	Placebo capsule given orally QOD during the 6-month, double-blind, randomized placebo-controlled treatment period (Stage 1). Migalastat 150-mg capsule given orally QOD during the 6-month open-label treatment period (Stage 2) and for up to 12 months during the OLE.	Total of all reporting groups
Overall Number of Baseline Participants		34	33	67
Baseline Analysis Population Description		Safety Population: All randomized participants who received at least 1 dose of study drug.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	34 participants	33 participants	67 participants
		40.0 (13.29)	44.5 (10.18)	42.2 (11.99)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	34 participants	33 participants	67 participants
	Female	22 64.7%	21 63.6%	43 64.2%
	Male	12 35.3%	12 36.4%	24 35.8%

Outcome Measures

1. Primary Outcome

Title	Percentage Of Participants With At Least A 50% Reduction From Baseline To Month 6 In The Average Number Of Kidney Interstitial Capillary (IC) Globotriaosylceramide (GL-3) Inclusions
Description	Renal biopsies were taken at Baseline and Month 6 (Stage 1). The specimens were evaluated using virtual microscopy. The annotation, scoring, and adjudication of the kidney histology assessments were performed by the Clinical Pathology Endpoints Committee. The number of kidney IC GL-3 inclusions was assessed by 3 renal pathologists who were blinded to treatment assignments, participants' data, and biopsy sequence. One pathologist served as annotator and identified the 300 capillaries on up to 8 slides per specimen to be scored. Two pathologists served as scorers; these pathologists completed the blinded paired assessments. Each pathologist served as annotator/adjudicator for 1/3 of the cases. Paired assessments were undertaken at Baseline and Month 6. Assessments were made using digital images. A responder was defined as a participant with a ≥50% reduction from Baseline to Month 6 in the average number of kidney IC GL-3 inclusions.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

ITT: All randomized participants regardless of their participation in the study beyond randomization. As per the statistical analysis plan, analysis excluded participants who were missing baseline kidney biopsy results.

Arm/Group Title	Migalastat	Placebo
Arm/Group Description:	Migalastat 150-mg capsule given orally QOD during the 6-month, double-blind, randomized placebo-controlled treatment period (Stage 1).	Placebo capsule given orally QOD during the 6-month, double-blind, randomized placebo-controlled treatment period (Stage 1).
Overall Number of Participants Analyzed	32	32
Measure Type: Count of Participants; Unit of Measure: Participants
Responder	13 40.6%	9 28.1%
Non-Responder	19 59.4%	23 71.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Migalastat, Placebo
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2996
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	p-value from Cochran-Mantel-Haenszel test stratified by sex
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	12.5
	Confidence Interval	(2-Sided) 95%; -13.4 to 37.3
	Estimation Comments	The difference between the percentage of successes between migalastat and placebo treatment groups

2. Secondary Outcome

Title	Percent Change In Kidney IC GL-3 Inclusions From Baseline To Month 6
Description	Renal biopsies were taken at Baseline and Month 6. The specimens were evaluated using virtual microscopy. The annotation, scoring, and adjudication of the kidney histology assessments were performed by the Clinical Pathology Endpoints Committee. The number of kidney IC GL-3 inclusions was assessed by 3 renal pathologists who were blinded to treatment assignments, participants' data, and biopsy sequence. One pathologist served as annotator and identified the 300 capillaries on up to 8 slides per specimen to be scored. Two pathologists served as scorers; these pathologists completed the blinded paired assessments. Each pathologist served as annotator/adjudicator for 1/3 of the cases. Paired assessments were undertaken at Baseline and Month 6. Assessments were made using digital images.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

ITT: All randomized participants regardless of their participation in the study beyond randomization.

Arm/Group Title	Migalastat	Placebo
Arm/Group Description:	Migalastat 150-mg capsule given orally QOD during the 6-month, double-blind, randomized placebo-controlled treatment period (Stage 1).	Placebo capsule given orally QOD during the 6-month, double-blind, randomized placebo-controlled treatment period (Stage 1).
Overall Number of Participants Analyzed	34	33
Mean (Standard Deviation); Unit of Measure: percent change
	-7.948 (105.2736)	12.985 (90.5131)

3. Secondary Outcome

Title	Change From Baseline Through Month 24 In Urine GL-3 Levels
Description	The effect of migalastat versus placebo on urine GL-3 levels was measured by liquid chromatography-mass spectrometry/mass spectrometry. The 24-hour urine samples were collected at Baseline, Month 6 (Stage 1), Month 12 (Stage 2), and Month 24 (OLE). Results are presented as changes in nanograms (ng)/mg creatinine from Baseline to the end of the 3 stages.
Time Frame	Baseline, Months 6, 12, and 24

Outcome Measure Data

Analysis Population Description

Stage 1: ITT, all randomized participants regardless of participation in the study beyond randomization. Stage 2: participants who completed Stage 1 and entered Stage 2. OLE: participants who completed Stage 2 and entered the optional OLE. Once assay and sample issues were identified, later samples were not further analyzed; all data was listed.

Arm/Group Title		Migalastat-Migalastat	Placebo-Migalastat
Arm/Group Description:		Migalastat 150-mg capsule given orally QOD during the 6-month, double-blind, randomized placebo-controlled treatment period (Stage 1), during the 6-month open-label treatment period (Stage 2), and for up to 12 months during the OLE.	Placebo capsule given orally QOD during the 6-month, double-blind, randomized placebo-controlled treatment period (Stage 1). Migalastat 150-mg capsule given orally QOD during the 6-month open-label treatment period (Stage 2) and for up to 12 months during the OLE.
Overall Number of Participants Analyzed		33	30
Mean (Standard Deviation); Unit of Measure: ng/mg creatinine
Stage 1	Number Analyzed	33 participants	30 participants
		-234.80 (853.451)	-186.24 (957.119)
Stage 2	Number Analyzed	31 participants	28 participants
		-179.63 (699.157)	-537.95 (1169.883)
OLE	Number Analyzed	12 participants	9 participants
		-62.37 (615.944)	-177.42 (288.224)

4. Other Pre-specified Outcome

Title	Change From Month 6 To Month 12 In Average Number Of Kidney IC GL-3 Inclusions
Description	Renal biopsies were taken at Month 6 and Month 12. The specimens were evaluated using virtual microscopy. The annotation, scoring, and adjudication of the kidney histology assessments were performed by the Clinical Pathology Endpoints Committee. The number of kidney IC GL-3 inclusions was assessed by 3 renal pathologists who were blinded to treatment assignments, participants' data, and biopsy sequence. One pathologist served as annotator and identified the 300 capillaries on up to 8 slides per specimen to be scored. Two pathologists served as scorers; these pathologists completed the blinded paired assessments. Each pathologist served as annotator/adjudicator for 1/3 of the cases. Paired assessments were undertaken at Month 6 and Month 12. Assessments were made using digital images.
Time Frame	Month 6, Month 12

Outcome Measure Data

Analysis Population Description

mITT with amenable mutations: Randomized participants who switched from placebo to migalastat during Stage 2, received at least 1 dose of study drug, and underwent a renal biopsy at both Baseline and Month 6. Amenable mutations are mutant forms of α-galactosidase A (α Gal-A) amenable to migalastat. Amenable mutations based on the GLP HEK assay.

Arm/Group Title	Placebo-Migalastat
Arm/Group Description:	Placebo capsule given orally QOD during the 6-month, double-blind, randomized placebo-controlled treatment period (Stage 1). Migalastat 150-mg capsule given orally QOD during the 6-month open-label treatment period (Stage 2).
Overall Number of Participants Analyzed	20
Least Squares Mean (95% Confidence Interval); Unit of Measure: kidney IC GL-3 inclusions
	-0.320; (-0.5719 to -0.0677)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo-Migalastat
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	Mixed effects model for repeated measures (MMRM) approach with fixed effects of treatment, time (Month 6 and Month 12), mutation type (amenable or non-amenable), time by treatment interaction, time by mutation type interaction, and the baseline value as a covariate. An unstructured covariance matrix to account for repeated measures within a participant was assumed.
Statistical Test of Hypothesis	P-Value	0.014
	Comments	Significant at the 0.050 level
	Method	MMRM
	Comments	[Not Specified]

5. Post-Hoc Outcome

Title	Change From Baseline To Month 6 In Average Number Of Kidney IC GL-3 Inclusions
Description	Renal biopsies were taken at Baseline and Month 6. The specimens were evaluated using virtual microscopy. The annotation, scoring, and adjudication of the kidney histology assessments were performed by the Clinical Pathology Endpoints Committee. The number of kidney IC GL-3 inclusions was assessed by 3 renal pathologists who were blinded to treatment assignments, participants' data, and biopsy sequence. One pathologist served as annotator and identified the 300 capillaries on up to 8 slides per specimen to be scored. Two pathologists served as scorers; these pathologists completed the blinded paired assessments. Each pathologist served as annotator/adjudicator for 1/3 of the cases. Paired assessments were undertaken at Baseline and Month 6. Assessments were made using digital images. Treatment effect was estimated using the LS mean difference between treatments within the context of the ANCOVA model.
Time Frame	Baseline, Month 6

Outcome Measure Data

Analysis Population Description

ITT-amenable: Randomized participants with amenable mutations who received study drug during Stage 1. Amenable mutations are mutant forms of α Gal-A amenable to migalastat. Amenable mutations based on the GLP HEK assay. Participants were analyzed according to their original randomized treatment group.

Arm/Group Title	Migalastat
Arm/Group Description:	Migalastat 150-mg capsule given orally QOD during the 6-month, double-blind, randomized placebo-controlled treatment period (Stage 1).
Overall Number of Participants Analyzed	25
Mean (Standard Deviation); Unit of Measure: kidney IC GL-3 inclusions
	-0.250 (0.5126)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Migalastat
	Comments	The change from Baseline in the average number of kidney ICs was analyzed using an ANCOVA model with covariate adjustment for the baseline value and factors for treatment group and the treatment by baseline interaction.
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0078
	Comments	Significant at the 0.010 level
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference LSMeans
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.6 to -0.1
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Adverse events (AEs) were monitored up to 25 months (±7 days) after the first dose of study drug. AEs were reported from the first dose of study medication at Baseline (Visit 1) in Stage 1 to 1 month (±7 days) after the date of the last study visit, whether during Stage 1, Stage 2, or the optional OLE, or after premature discontinuation from the study.
Adverse Event Reporting Description	Stage 1 AEs were any AEs that started between the first dose of Stage 1 and the first dose of Stage 2 (or last Stage 1 administration for participants that discontinued during Stage 1). Stage 2 AEs were any AEs that started between the first dose of Stage 2 and the first dose of the OLE (or the last Stage 2 administration for participants that discontinued during Stage 2). OLE AEs were any AEs that started after the first dose of the OLE.
Arm/Group Title	Migalastat (0-6 Months)	Placebo (0-6 Months)	All Migalastat (>6-12 Months)	All Migalastat (>12-24 Months)
Arm/Group Description	Migalastat 150-mg capsule given orally QOD during the 6-month, double-blind, randomized placebo-controlled treatment period (Stage 1). After Stage 1, participants progressed to Stage 2 where they received open-label migalastat for 6 months.	Placebo capsule given orally QOD during the 6-month, double-blind, randomized placebo-controlled treatment period (Stage 1). After Stage 1, participants progressed to Stage 2 where they received open-label migalastat for 6 months.	Migalastat 150-mg capsule given orally QOD during the 6-month open-label treatment period (Stage 2). Includes all participants who progressed from both the migalastat (0-6 Months) and the placebo (0-6 Months) Stage 1 treatment groups. After Stage 2, participants were eligible to enter the optional, 12-month OLE.	Migalastat 150-mg capsule given orally QOD for up to 12 months during the optional OLE. Includes all participants who decided to continue treatment after completing the 6-month, open-label Stage 2 treatment period.
All-Cause Mortality
	Migalastat (0-6 Months)	Placebo (0-6 Months)	All Migalastat (>6-12 Months)	All Migalastat (>12-24 Months)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--
Serious Adverse Events
	Migalastat (0-6 Months)	Placebo (0-6 Months)	All Migalastat (>6-12 Months)	All Migalastat (>12-24 Months)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/34 (5.88%)	4/33 (12.12%)	5/63 (7.94%)	11/57 (19.30%)
Cardiac disorders
Palpitations † 1	0/34 (0.00%)	0/33 (0.00%)	0/63 (0.00%)	1/57 (1.75%)
Ventricular Tachycardia † 1	0/34 (0.00%)	0/33 (0.00%)	1/63 (1.59%)	0/57 (0.00%)
Gastrointestinal disorders
Abdominal Pain Lower † 1	0/34 (0.00%)	0/33 (0.00%)	0/63 (0.00%)	1/57 (1.75%)
Constipation † 1	0/34 (0.00%)	0/33 (0.00%)	0/63 (0.00%)	1/57 (1.75%)
General disorders
Fatigue † 1	0/34 (0.00%)	0/33 (0.00%)	0/63 (0.00%)	1/57 (1.75%)
Malaise † 1	0/34 (0.00%)	0/33 (0.00%)	0/63 (0.00%)	1/57 (1.75%)
Non-cardiac chest pain † 1	0/34 (0.00%)	0/33 (0.00%)	0/63 (0.00%)	1/57 (1.75%)
Infections and infestations
Bacterial Infection † 1	0/34 (0.00%)	1/33 (3.03%)	0/63 (0.00%)	0/57 (0.00%)
Helicobacter Gastritis † 1	0/34 (0.00%)	0/33 (0.00%)	0/63 (0.00%)	1/57 (1.75%)
Meningitis Viral † 1	0/34 (0.00%)	1/33 (3.03%)	0/63 (0.00%)	0/57 (0.00%)
Injury, poisoning and procedural complications
Multiple Fractures † 1	0/34 (0.00%)	0/33 (0.00%)	0/63 (0.00%)	1/57 (1.75%)
Post Procedural Haematoma † 1	1/34 (2.94%)	0/33 (0.00%)	0/63 (0.00%)	0/57 (0.00%)
Post Procedural Haemorrhage † 1	0/34 (0.00%)	1/33 (3.03%)	0/63 (0.00%)	0/57 (0.00%)
Musculoskeletal and connective tissue disorders
Bone Cyst † 1	0/34 (0.00%)	0/33 (0.00%)	1/63 (1.59%)	0/57 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anaplastic Large Cell Lymphoma T - and Null - Cell Types † 1	0/34 (0.00%)	1/33 (3.03%)	0/63 (0.00%)	0/57 (0.00%)
Nervous system disorders
Amyotrophic Lateral Sclerosis † 1	0/34 (0.00%)	0/33 (0.00%)	1/63 (1.59%)	0/57 (0.00%)
Cerebral Haemorrhage † 1	0/34 (0.00%)	0/33 (0.00%)	1/63 (1.59%)	0/57 (0.00%)
Syncope † 1	0/34 (0.00%)	0/33 (0.00%)	0/63 (0.00%)	1/57 (1.75%)
Paraesthesia † 1	0/34 (0.00%)	0/33 (0.00%)	0/63 (0.00%)	1/57 (1.75%)
Transient Ischaemic Attack † 1	0/34 (0.00%)	0/33 (0.00%)	0/63 (0.00%)	1/57 (1.75%)
Psychiatric disorders
Bulimia Nervosa † 1	0/34 (0.00%)	0/33 (0.00%)	1/63 (1.59%)	0/57 (0.00%)
Renal and urinary disorders
Hydronephrosis † 1	1/34 (2.94%)	0/33 (0.00%)	0/63 (0.00%)	0/57 (0.00%)
Respiratory, thoracic and mediastinal disorders
Pneumothorax † 1	0/34 (0.00%)	0/33 (0.00%)	0/63 (0.00%)	1/57 (1.75%)
Pulmonary Embolism † 1	0/34 (0.00%)	0/33 (0.00%)	2/63 (3.17%)	0/57 (0.00%)
Vascular disorders
Deep Vein Thrombosis † 1	0/34 (0.00%)	0/33 (0.00%)	1/63 (1.59%)	0/57 (0.00%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 15.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Migalastat (0-6 Months)	Placebo (0-6 Months)	All Migalastat (>6-12 Months)	All Migalastat (>12-24 Months)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	31/34 (91.18%)	30/33 (90.91%)	50/63 (79.37%)	46/57 (80.70%)
Cardiac disorders
Atrial Fibrillation † 1	2/34 (5.88%)	0/33 (0.00%)	1/63 (1.59%)	3/57 (5.26%)
Ear and labyrinth disorders
Vertigo † 1	2/34 (5.88%)	3/33 (9.09%)	3/63 (4.76%)	0/57 (0.00%)
Gastrointestinal disorders
Abdominal Pain Upper † 1	2/34 (5.88%)	0/33 (0.00%)	2/63 (3.17%)	2/57 (3.51%)
Constipation † 1	2/34 (5.88%)	2/33 (6.06%)	1/63 (1.59%)	2/57 (3.51%)
Dry Mouth † 1	2/34 (5.88%)	2/33 (6.06%)	0/63 (0.00%)	0/57 (0.00%)
Diarrhoea † 1	3/34 (8.82%)	1/33 (3.03%)	5/63 (7.94%)	2/57 (3.51%)
Nausea † 1	4/34 (11.76%)	2/33 (6.06%)	2/63 (3.17%)	3/57 (5.26%)
Vomiting † 1	1/34 (2.94%)	2/33 (6.06%)	1/63 (1.59%)	3/57 (5.26%)
Abdominal Distension † 1	2/34 (5.88%)	1/33 (3.03%)	2/63 (3.17%)	0/57 (0.00%)
General disorders
Fatigue † 1	4/34 (11.76%)	4/33 (12.12%)	2/63 (3.17%)	3/57 (5.26%)
Pyrexia † 1	4/34 (11.76%)	1/33 (3.03%)	1/63 (1.59%)	0/57 (0.00%)
Asthenia † 1	2/34 (5.88%)	1/33 (3.03%)	0/63 (0.00%)	1/57 (1.75%)
Infections and infestations
Bronchitis † 1	1/34 (2.94%)	0/33 (0.00%)	1/63 (1.59%)	6/57 (10.53%)
Influenza † 1	0/34 (0.00%)	3/33 (9.09%)	0/63 (0.00%)	2/57 (3.51%)
Nasopharyngitis † 1	6/34 (17.65%)	2/33 (6.06%)	5/63 (7.94%)	3/57 (5.26%)
Upper Respiratory Tract Infection † 1	2/34 (5.88%)	3/33 (9.09%)	5/63 (7.94%)	3/57 (5.26%)
Urinary Tract Infection † 1	2/34 (5.88%)	0/33 (0.00%)	3/63 (4.76%)	5/57 (8.77%)
Cystitis † 1	2/34 (5.88%)	0/33 (0.00%)	0/63 (0.00%)	0/57 (0.00%)
Injury, poisoning and procedural complications
Overdose † 1	2/34 (5.88%)	1/33 (3.03%)	0/63 (0.00%)	0/57 (0.00%)
Procedural Pain † 1	2/34 (5.88%)	1/33 (3.03%)	7/63 (11.11%)	0/57 (0.00%)
Post Procedural Complication † 1	2/34 (5.88%)	0/33 (0.00%)	1/63 (1.59%)	0/57 (0.00%)
Investigations
Weight Increased † 1	2/34 (5.88%)	1/33 (3.03%)	0/63 (0.00%)	0/57 (0.00%)
Metabolism and nutrition disorders
Vitamin D Deficiency † 1	1/34 (2.94%)	1/33 (3.03%)	1/63 (1.59%)	3/57 (5.26%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/34 (0.00%)	2/33 (6.06%)	4/63 (6.35%)	5/57 (8.77%)
Muscle Spasms † 1	1/34 (2.94%)	3/33 (9.09%)	2/63 (3.17%)	1/57 (1.75%)
Back Pain † 1	3/34 (8.82%)	0/33 (0.00%)	2/63 (3.17%)	3/57 (5.26%)
Myalgia † 1	2/34 (5.88%)	1/33 (3.03%)	1/63 (1.59%)	2/57 (3.51%)
Pain In Extremity † 1	0/34 (0.00%)	4/33 (12.12%)	2/63 (3.17%)	2/57 (3.51%)
Torticollis † 1	2/34 (5.88%)	0/33 (0.00%)	0/63 (0.00%)	0/57 (0.00%)
Nervous system disorders
Dizziness † 1	2/34 (5.88%)	1/33 (3.03%)	2/63 (3.17%)	1/57 (1.75%)
Paraesthesia † 1	4/34 (11.76%)	4/33 (12.12%)	4/63 (6.35%)	2/57 (3.51%)
Headache † 1	12/34 (35.29%)	7/33 (21.21%)	9/63 (14.29%)	6/57 (10.53%)
Hypoaesthesia † 1	2/34 (5.88%)	0/33 (0.00%)	2/63 (3.17%)	0/57 (0.00%)
Psychiatric disorders
Depression † 1	1/34 (2.94%)	0/33 (0.00%)	3/63 (4.76%)	4/57 (7.02%)
Insomnia † 1	3/34 (8.82%)	2/33 (6.06%)	0/63 (0.00%)	0/57 (0.00%)
Renal and urinary disorders
Proteinuria † 1	0/34 (0.00%)	0/33 (0.00%)	1/63 (1.59%)	9/57 (15.79%)
Haematuria † 1	3/34 (8.82%)	0/33 (0.00%)	1/63 (1.59%)	0/57 (0.00%)
Microalbuminuria † 1	0/34 (0.00%)	0/33 (0.00%)	0/63 (0.00%)	3/57 (5.26%)
Respiratory, thoracic and mediastinal disorders
Epistaxis † 1	3/34 (8.82%)	1/33 (3.03%)	1/63 (1.59%)	0/57 (0.00%)
Cough † 1	3/34 (8.82%)	0/33 (0.00%)	1/63 (1.59%)	2/57 (3.51%)
Oropharyngeal Pain † 1	3/34 (8.82%)	2/33 (6.06%)	0/63 (0.00%)	2/57 (3.51%)
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 15.0

Limitations and Caveats

During Phase 3, prior to unblinding, the assay used for enrollment was validated (GLP HEK assay). Mutant forms of α-Gal A that met assay criteria were categorized as amenable; additional analyses were subsequently performed on this target population.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The investigator can publish only the results from this trial, provided they supply the sponsor (or authorized entity) a copy of any proposed publication for review prior to submission for publication. If requested and prior to publication, the investigator will remove information deemed confidential or proprietary by the sponsor and will withhold publication for an additional period of time to allow the sponsor to take appropriate measures to establish and preserve its proprietary rights.

Results Point of Contact

• Name/Title: Medical Affairs
• Organization: Amicus Therapeutics
• Phone: +1-877-426-4287 (877-4-AMICUS)
• EMail: MedInfoUSA@amicusrx.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bichet DG, Aerts JM, Auray-Blais C, Maruyama H, Mehta AB, Skuban N, Krusinska E, Schiffmann R. Assessment of plasma lyso-Gb3 for clinical monitoring of treatment response in migalastat-treated patients with Fabry disease. Genet Med. 2021 Jan;23(1):192-201. doi: 10.1038/s41436-020-00968-z. Epub 2020 Sep 30. Erratum In: Genet Med. 2020 Nov 20;:

Germain DP, Nicholls K, Giugliani R, Bichet DG, Hughes DA, Barisoni LM, Colvin RB, Jennette JC, Skuban N, Castelli JP, Benjamin E, Barth JA, Viereck C. Efficacy of the pharmacologic chaperone migalastat in a subset of male patients with the classic phenotype of Fabry disease and migalastat-amenable variants: data from the phase 3 randomized, multicenter, double-blind clinical trial and extension study. Genet Med. 2019 Sep;21(9):1987-1997. doi: 10.1038/s41436-019-0451-z. Epub 2019 Feb 6.

Schiffmann R, Bichet DG, Jovanovic A, Hughes DA, Giugliani R, Feldt-Rasmussen U, Shankar SP, Barisoni L, Colvin RB, Jennette JC, Holdbrook F, Mulberg A, Castelli JP, Skuban N, Barth JA, Nicholls K. Migalastat improves diarrhea in patients with Fabry disease: clinical-biomarker correlations from the phase 3 FACETS trial. Orphanet J Rare Dis. 2018 Apr 27;13(1):68. doi: 10.1186/s13023-018-0813-7.

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.

Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR, Feliciani C, Shankar SP, Ezgu F, Amartino H, Bratkovic D, Feldt-Rasmussen U, Nedd K, Sharaf El Din U, Lourenco CM, Banikazemi M, Charrow J, Dasouki M, Finegold D, Giraldo P, Goker-Alpan O, Longo N, Scott CR, Torra R, Tuffaha A, Jovanovic A, Waldek S, Packman S, Ludington E, Viereck C, Kirk J, Yu J, Benjamin ER, Johnson F, Lockhart DJ, Skuban N, Castelli J, Barth J, Barlow C, Schiffmann R. Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat. N Engl J Med. 2016 Aug 11;375(6):545-55. doi: 10.1056/NEJMoa1510198.

• Responsible Party: Amicus Therapeutics
• ClinicalTrials.gov Identifier: NCT00925301
• Other Study ID Numbers: AT1001-011; FACETS ( Other Identifier: Amicus Therapeutics ); 2009-013459-31 ( EudraCT Number )
• First Submitted: June 19, 2009
• First Posted: June 22, 2009
• Results First Submitted: August 10, 2018
• Results First Posted: October 30, 2018
• Last Update Posted: October 30, 2018