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NCT00925301

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

Completed Phase 3 Results posted Last updated 30 October 2018
What this trial tests

Phase 3 trial testing migalastat hydrochloride in Fabry Disease in 67 participants. Completed in 29 January 2014.

Timeline
23 October 2009
Primary endpoint
12 June 2012
29 January 2014

Quick facts

Lead sponsorAmicus Therapeutics
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment67
Start date23 October 2009
Primary completion12 June 2012
Estimated completion29 January 2014
Sites28 locations across Denmark, France, Italy, Turkey (Türkiye), United Kingdom, Poland, Argentina, Canada

Drugs / interventions tested

Conditions studied

Sponsor

Amicus Therapeutics — full company profile →

Who can join

Adults 16 to 74, any sex, 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.

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 Primary · Baseline, Month 6

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 th

GroupValue95% CI
Migalastat13
Placebo9
Migalastat19
Placebo23
Percent Change In Kidney IC GL-3 Inclusions From Baseline To Month 6 Secondary · Baseline, Month 6

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

GroupValue95% CI
Migalastat-7.948± 105.2736
Placebo12.985± 90.5131
Change From Baseline Through Month 24 In Urine GL-3 Levels Secondary · Baseline, Months 6, 12, and 24

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.

Stage 1
GroupValue95% CI
Migalastat-Migalastat-234.80± 853.451
Placebo-Migalastat-186.24± 957.119
Stage 2
GroupValue95% CI
Migalastat-Migalastat-179.63± 699.157
Placebo-Migalastat-537.95± 1169.883
OLE
GroupValue95% CI
Migalastat-Migalastat-62.37± 615.944
Placebo-Migalastat-177.42± 288.224
Change From Month 6 To Month 12 In Average Number Of Kidney IC GL-3 Inclusions Secondary · Month 6, Month 12

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

GroupValue95% CI
Placebo-Migalastat-0.320-0.5719 – -0.0677
Change From Baseline To Month 6 In Average Number Of Kidney IC GL-3 Inclusions Secondary · Baseline, Month 6

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

GroupValue95% CI
Migalastat-0.250± 0.5126

Adverse events — posted to ClinicalTrials.gov

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.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Migalastat (0-6 Months)
Serious: 2/34 (6%)
Deaths:
Placebo (0-6 Months)
Serious: 4/33 (12%)
Deaths:
All Migalastat (>6-12 Months)
Serious: 5/63 (8%)
Deaths:
All Migalastat (>12-24 Months)
Serious: 11/57 (19%)
Deaths:

Serious adverse events (25 terms)

ReactionSystemMigalastat (0-6 Months)Placebo (0-6 Months)All Migalastat (>6-12 Mont…All Migalastat (>12-24 Mon…
Pulmonary EmbolismRespiratory, thoracic and mediastinal disorders
Deep Vein ThrombosisVascular disorders
Multiple FracturesInjury, poisoning and procedural complications
Post Procedural HaematomaInjury, poisoning and procedural complications
Post Procedural HaemorrhageInjury, poisoning and procedural complications
Anaplastic Large Cell Lymphoma T - and Null - Cell TypesNeoplasms benign, malignant and unspecified (incl cysts and polyps)
PalpitationsCardiac disorders
Ventricular TachycardiaCardiac disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
Amyotrophic Lateral SclerosisNervous system disorders
Cerebral HaemorrhageNervous system disorders
SyncopeNervous system disorders
ParaesthesiaNervous system disorders
Transient Ischaemic AttackNervous system disorders
FatigueGeneral disorders
MalaiseGeneral disorders
Non-cardiac chest painGeneral disorders
Bulimia NervosaPsychiatric disorders
Abdominal Pain LowerGastrointestinal disorders
ConstipationGastrointestinal disorders
HydronephrosisRenal and urinary disorders
Bone CystMusculoskeletal and connective tissue disorders
Bacterial InfectionInfections and infestations
Helicobacter GastritisInfections and infestations
Meningitis ViralInfections and infestations
Other adverse events (41 terms — click to expand)

ReactionSystemMigalastat (0-6 Months)Placebo (0-6 Months)All Migalastat (>6-12 Mont…All Migalastat (>12-24 Mon…
HeadacheNervous system disorders
ProteinuriaRenal and urinary disorders
Procedural PainInjury, poisoning and procedural complications
BronchitisInfections and infestations
NasopharyngitisInfections and infestations
DiarrhoeaGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Upper Respiratory Tract InfectionInfections and infestations
Urinary Tract InfectionInfections and infestations
FatigueGeneral disorders
PyrexiaGeneral disorders
DepressionPsychiatric disorders
ParaesthesiaNervous system disorders
NauseaGastrointestinal disorders
Pain In ExtremityMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Oropharyngeal PainRespiratory, thoracic and mediastinal disorders
VertigoEar and labyrinth disorders
VomitingGastrointestinal disorders
HaematuriaRenal and urinary disorders
Muscle SpasmsMusculoskeletal and connective tissue disorders
Back PainMusculoskeletal and connective tissue disorders
InfluenzaInfections and infestations
Atrial FibrillationCardiac disorders
Vitamin D DeficiencyMetabolism and nutrition disorders
MicroalbuminuriaRenal and urinary disorders
OverdoseInjury, poisoning and procedural complications
DizzinessNervous system disorders
Abdominal Pain UpperGastrointestinal disorders
ConstipationGastrointestinal disorders
Dry MouthGastrointestinal disorders
MyalgiaMusculoskeletal and connective tissue disorders
Abdominal DistensionGastrointestinal disorders
AstheniaGeneral disorders
CystitisInfections and infestations
Post Procedural ComplicationInjury, poisoning and procedural complications
Weight IncreasedInvestigations
TorticollisMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Pulmonary Embolism, Deep Vein Thrombosis, Multiple Fractures, Post Procedural Haematoma, Post Procedural Haemorrhage, Anaplastic Large Cell Lymphoma T - and Null - Cell Types, Palpitations, Ventricular Tachycardia.

Data from ClinicalTrials.gov NCT00925301 adverse events section.

Sponsor's own description

The primary objective of this study was to compare the effect of migalastat (123 milligrams \[mg\] of migalastat \[equivalent to 150 mg of migalastat hydrochloride\]) (migalastat) versus placebo on kidney globotriaosylceramide (GL-3).

Publications & conference data

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

  1. Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat.
    Germain DP, Hughes DA, Nicholls K, Bichet DG, et al · · 2016 · cited 370× · PMID 27509102 · DOI 10.1056/nejmoa1510198
  2. Drug development in the era of precision medicine.
    Dugger SA, Platt A, Goldstein DB. · · 2018 · cited 296× · PMID 29217837 · DOI 10.1038/nrd.2017.226
  3. Oral pharmacological chaperone migalastat compared with enzyme replacement therapy in Fabry disease: 18-month results from the randomised phase III ATTRACT study.
    Hughes DA, Nicholls K, Shankar SP, Sunder-Plassmann G, et al · · 2017 · cited 258× · PMID 27834756 · DOI 10.1136/jmedgenet-2016-104178
  4. 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
  5. Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients.
    Germain DP, Fouilhoux A, Decramer S, Tardieu M, et al · · 2019 · cited 112× · PMID 30941742 · DOI 10.1111/cge.13546
  6. 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.
    Germain DP, Nicholls K, Giugliani R, Bichet DG, et al · · 2019 · cited 73× · PMID 30723321 · DOI 10.1038/s41436-019-0451-z
  7. Enzyme replacement therapy for Anderson-Fabry disease.
    El Dib R, Gomaa H, Carvalho RP, Camargo SE, et al · · 2016 · cited 64× · PMID 27454104 · DOI 10.1002/14651858.cd006663.pub4
  8. Pharmaceutical Chaperones and Proteostasis Regulators in the Therapy of Lysosomal Storage Disorders: Current Perspective and Future Promises.
    Mohamed FE, Al-Gazali L, Al-Jasmi F, Ali BR. · · 2017 · cited 45× · PMID 28736525 · DOI 10.3389/fphar.2017.00448

Verify or expand the search:

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00925301.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing