A Phase 2 interventional study of migalastat HCl in Fabry Disease, sponsored by Amicus Therapeutics. Terminated at 8 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2018-10-03.
Sponsored by Amicus Therapeutics · Phase 2, Interventional, and Treatment
Study to evaluate the long-term safety, tolerability, and pharmacodynamics (PD) of migalastat hydrochloride (HCl) (migalastat) in participants with Fabry disease
This was a long-term open-label study of migalastat in participants with Fabry disease who were previously enrolled in a Phase 2 study of migalastat (FAB-CL-201 [NCT00214500], FAB-CL-202 [NCT00283959], FAB-CL-203 [NCT00283933], or FAB-CL-204 [NCT00304512]). Participants could enter this extension study immediately upon completion of participation in their previous study of migalastat, or at a later time point. Thus, some participants did not necessarily have continuous treatment with migalastat from the end of the original study to the time of enrollment into this extension study. Participants who enrolled before Protocol Amendment 2 received migalastat 150 milligrams (mg) orally once every other day (QOD). After the amendment, these participants entered a dose escalation period (DEP) at their next scheduled visit. During the DEP, participants received migalastat 250 mg (once daily [QD] for 3 days and 4 days off per week) for the first 2 months. If there were no safety concerns, the dose was then increased to 500 mg QD for 3 days and 4 days off per week). Participants received 500 mg (QD for 3 days and 4 days off per week) for up to 10 months, depending on the approval date of the protocol amendments at each site. An interim review of safety and PD data was performed after all enrolled participants had completed at least 4 months of treatment in the DEP. After the review, the dose and regimen of migalastat was returned to 150 mg QOD for all participants, except those who were on another dose as previously agreed by the investigator and medical monitor.
The sponsor (Amicus Therapeutics) discontinued Study FAB-CL-205 for logistical reasons and not due to either safety concerns or lack of efficacy. Participants who were ongoing in Study FAB-CL-205 at the time of discontinuation were offered participation in another open-label, long-term treatment study of migalastat (AT1001-041 [NCT01458119]). Participants who did not enroll in Study AT1001-041 were contacted by telephone or another suitable method approximately 1 month after the End of Study (EOS) visit to inquire about adverse events and concomitant medications.
242 studies on the registry are indexed under Fabry Disease; 54 are open to participants now.
This study's enrollment of 23 is close to the median of 22 across 105 interventional studies indexed under Fabry Disease.
Browse Fabry Disease studies →Amicus Therapeutics is the lead sponsor of 42 studies on the registry; 8 are open to participants now.
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Migalastat was administered orally, 150 mg QOD, 250 mg QD for 3 days, 4 days off per week for 2 months, or 500 mg QD for 3 days, 4 days off per week for up to 10 months, depending on the approval date of the protocol amendments at each site. Participants received migalastat for up to 56 months.
Drug: migalastat HCl
Also known as: AT1001, Galafold, migalastat
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
A TEAE was defined as any adverse event (AE) 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 AE was defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through End of Study (EOS) or follow-up (for participants who did not enroll in Study AT1001-041) are presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time frame: Day 1 (after dosing) through EOS (up to 56 months) or follow-up (28 days after EOS)
Absolute Change From Baseline In α-Galactosidase A (α-Gal A) Activity In Leukocytes To Month 42
The activity of the α-Gal A enzyme was measured in leukocyte lysate by a validated fluorometric assay method, using 4-methylumbelliferone as a reference. The activity values obtained were normalized to protein (measured using a colorimetric assay). Baseline was defined as the last non-missing pre-treatment value for each participant in his or her respective preceding migalastat Phase 2 study. A negative change from Baseline indicates that α-Gal A activity decreased. α-Gal A activity levels are presented for Baseline and Month 42.
Time frame: Baseline, Month 42
Pharmacokinetics Of Migalastat As Assessed By Plasma Concentration
The concentration of migalastat was evaluated in plasma following a dose of 250 mg and 500 mg. Blood samples were taken at trough (predose or Time 0; just prior to the third dose during a 3 day on, 4 days off dosing regimen) and at peak (3 hr postdose; after the third dose during a 3 day on, 4 days off dosing regimen) during the Day 1 (250 mg) and Month 2 (500 mg) visits. This outcome presents the lowest and highest concentrations of migalastat measured in any of the participants for predose and 3 hr postdose.
Time frame: 0 (predose on Day 1; start of DEP), 3 hr (postdose at Month 2; during DEP])
An open label, long-term extension study for participants who completed one of 4 preceding Phase 2 studies (FAB-CL-201 \[NCT00214500\], FAB-CL-202 \[NCT00283959\], FAB-CL-203 \[NCT00283933\], or FAB-CL-204 \[NCT00304512\]). Participants could enter this study directly upon completion of the previous study or at a later point.
| Milestone | Migalastat |
|---|---|
| Started | 23 |
| Safety population | 23 |
| Pharmacodynamic (pd) population | 23 |
| Amenable population; men | 11 |
| Amenable population; women | 5 |
| Non-amenable population; men | 3 |
| Non-amenable population; women | 4 |
| Completed | 17 |
| Not completed | 6 |
| Withdrew: Adverse event | 1 |
| Withdrew: Withdrawal by subject | 1 |
| Withdrew: Lack of response to study drug | 4 |
A TEAE was defined as any adverse event (AE) 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 AE was defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through End of Study (EOS) or follow-up (for participants who did not enroll in Study AT1001-041) are presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
| Participants | Migalastat |
|---|---|
| Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) | 9 |
The activity of the α-Gal A enzyme was measured in leukocyte lysate by a validated fluorometric assay method, using 4-methylumbelliferone as a reference. The activity values obtained were normalized to protein (measured using a colorimetric assay). Baseline was defined as the last non-missing pre-treatment value for each participant in his or her respective preceding migalastat Phase 2 study. A negative change from Baseline indicates that α-Gal A activity decreased. α-Gal A activity levels are presented for Baseline and Month 42.
| nanomoles (nm)/hour (hr)/mg protein | Amenable Population; Men | Amenable Population; Women | Non-amenable Population; Men | Non-amenable Population; Women |
|---|---|---|---|---|
| Baseline | 2.08 ± 2.433 | 16.84 ± 7.955 | 0.09 ± 0.047 | 14.62 ± 8.944 |
| Month 42 | 7.88 ± 8.691 | 18.31 ± 14.186 | — | 9.77 ± 5.071 |
The concentration of migalastat was evaluated in plasma following a dose of 250 mg and 500 mg. Blood samples were taken at trough (predose or Time 0; just prior to the third dose during a 3 day on, 4 days off dosing regimen) and at peak (3 hr postdose; after the third dose during a 3 day on, 4 days off dosing regimen) during the Day 1 (250 mg) and Month 2 (500 mg) visits. This outcome presents the lowest and highest concentrations of migalastat measured in any of the participants for predose and 3 hr postdose.
| nanograms/milliliter | Migalastat |
|---|---|
| Predose Lowest Concentration | 5.94 |
| Predose Highest Concentration | 313 |
| 250 mg 3 hr Postdose Lowest Concentration | 908 |
| 250 mg 3 hr Postdose Highest Concentration | 5250 |
| 500 mg 3 hr Postdose Lowest Concentration | 113 |
| 500 mg 3 hr Postdose Highest Concentration | 8500 |
Collected over Day 1 after dosing through EOS (up to 56 months) or follow-up (28 days after EOS). Follow-up was not required for participants who enrolled in Study AT1001-041.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Migalastat | — | 7/23 (30.4%) | 23/23 (100%) |
| Event | Migalastat |
|---|---|
| Atrial FibrillationCardiac disorders | 2/23 |
| Atrial FlutterCardiac disorders | 1/23 |
| Atrioventricular BlockCardiac disorders | 1/23 |
| Cardiac Failure CongestiveCardiac disorders | 1/23 |
| Ventricular FibrillationCardiac disorders | 1/23 |
| HyperthyroidismEndocrine disorders | 1/23 |
| DyspepsiaGastrointestinal disorders | 1/23 |
| Sensation of Foreign BodyGeneral disorders | 1/23 |
| Ankle FractureInjury, poisoning and procedural complications | 1/23 |
| Post Procedural HaemorrhageInjury, poisoning and procedural complications | 1/23 |
| Event | Migalastat |
|---|---|
| ArthralgiaMusculoskeletal and connective tissue disorders | 9/23 |
| Back painMusculoskeletal and connective tissue disorders | 8/23 |
| FatigueGeneral disorders | 8/23 |
| InfluenzaInfections and infestations | 6/23 |
| Pain in extremityMusculoskeletal and connective tissue disorders | 6/23 |
| HeadacheNervous system disorders | 6/23 |
| NasopharyngitisInfections and infestations | 5/23 |
| SinusitisInfections and infestations | 5/23 |
| Abdominal pain upperGastrointestinal disorders | 5/23 |
| DiarrhoeaGastrointestinal disorders | 5/23 |
All participants who received at least 1 dose of study drug.
| Age, Continuous(years) | Migalastat |
|---|---|
| Mean | 43.1 ± 11.33 |
| Sex: Female, Male(Participants) | Migalastat |
|---|---|
| Female | 9 |
| Male | 14 |
This study is terminated, as verified in Oct 2018. You cannot join it, but the record below documents what was studied.
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Amicus Therapeutics