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

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

Population: 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.

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

Population: 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.

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

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

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

Population: 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.

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

Population: 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.