臨床研究等提出・公開システム

An Open-label Study to Evaluate the Safety and Pharmacokinetics of Migalastat HCl in Subjects with Fabry Disease and Amenable GLA Variants and Severe Renal Impairment or End-stage Renal Disease Treated with Hemodialysis

An Open-label Study to Evaluate the Safety and Pharmacokinetics of Migalastat HCl in Subjects with Fabry Disease and Renal dysfunctions

Koh KyuBum

Syneos Health Japan K K.

10F Umeda Daibiru, 3-3-10 Umeda, Kita-ku, Osaka

yoshinori.koh@syneoshealth.com

Koh KyuBum

Syneos Health Japan K K.

10F Umeda Daibiru, 3-3-10 Umeda, Kita-ku, Osaka

+81-80-3599-5902

yoshinori.koh@syneoshealth.com

Recruiting

Dec. 01, 2022

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

Subjects eligible for enrollment in the study must meet all of the following criteria:
1. Male or female subjects aged 18 years or older, diagnosed with Fabry disease.
2. Subject is willing and able to provide written informed consent and authorization for use and disclosure of Personal Health Information.
3. Subject has a GLA variant recorded in their medical records that is amenable to migalastat.
4. Subject has at least 1 documented eGFR value of < 30 mL/min/1.73 m2 within the last 3 months and has an eGFRMDRD value of < 30 mL/min/1.73 m2 at Visit 1 or subject is on HD (standard or HDF).
5. Subjects with ESRD have been on a stable 2- or 3-times a week HD (standard or HDF) regimen for at least 2 months prior to the screening visit.
6. Subjects with ESRD must commit to completing at least 4 standard HD or HDF sessions during each 2-week dosing interval.
7. Subjects with ESRD must commit to completing the entire prescribed duration for each dialysis session.
8. If of reproductive potential, both male and female patients agree to use a medically accepted method of contraception

Subjects meeting any of the following criteria are not eligible to be enrolled in the study:
1. Subject has undergone kidney transplantation.
2. Subject is on peritoneal dialysis.
3. Subject is treated or has been treated with another investigational drug (except migalastat) within the 30 days.
4. Subject has undergone any gene therapy at any time prior to the study or anticipates undergoing gene therapy during the study.
5. Subject has had a documented transient ischemic attack, stroke, unstable angina, or myocardial infarction.
6. Subject has clinically significant unstable cardiac disease.
7. Subject has any intercurrent illness or condition that may preclude the subject from fulfilling the protocol requirements.
8. Subject has a history of allergy or sensitivity to migalastat (including excipients) or other iminosugars (eg, miglustat, miglitol).
9. Subject requires concurrent treatment with Glyset (miglitol), Replagal (agalsidase alfa), or Fabrazyme (agalsidase beta).
10. Subject requires concurrent treatment with Zavesca (miglustat) or has been treated with Zavesca.
11. Female subject is pregnant or breastfeeding.
12. Subject is unable to comply with study requirements.

Both

Fabry Disease

Cohort 1: Severe Renal Impairment
All subjects will receive migalastat 123 mg, equivalent to 150 mgmigalastat HCl (hereafter, migalastat) at a dose regimen based on their eGFRMDRD result at Visit 1. Subjects will take 1 migalastat capsule orally with water either every 4 or 7 days.

Cohort 2: End-Stage Renal Disease
All hemodialysis subjects will receive migalastat 123 mg, equivalent to 150 mg migalastat HCl (hereafter, migalastat). Subjects will take 1 migalastat capsule orally with water every other week.

1.Maximum observed concentration (Cmax)
[Time Frame: Baseline through Month 12]
2.Time to maximum concentration (tmax)
[Time Frame: Baseline through Month 12]
3.Apparent terminal elimination half-life (t1/2)
[Time Frame: Baseline through Month 12]
4.Concentration at the end of a dosing interval at steady state (Ctrough)
[Time Frame: Baseline through Month 12]
5.Average plasma migalastat concentration over the dosing interval (Cavg)
[Time Frame: Baseline through Month 12]
6.Area under the concentration-time curve at steady state during the dosing interval (AUC0-T)
[TimeFrame: Baseline through Month 12]
7. Area under the concentration-time curve from zero time (pre-dose) extrapolated to infinite time (AUC0-inf.)
[TimeFrame: Baseline through Month 12]
8.Apparent plasma clearance (CL/F)
[Time Frame: Baseline through Month 12]
9.Apparent terminal phase volume of distribution (Vz/F)
[Time Frame: Baseline through Month 12]
10.Dialysis clearance (CLD)
[Time Frame: Baseline through Month 12]
11.Volume of dialysate collected during the interval (VD)
[Time Frame: Baseline through Month 12]
12.Mean migalastat concentration in dialysate (CD)
[Time Frame: Baseline through Month 12]
13.Amount recovered in dialysate (AeD)
[Time Frame: Baseline through Month 12]
14.Fraction of the dose recovered in dialysate (FeD)
[Time Frame: Baseline through Month 12]
15.Mean migalastat plasma concentration during the dialysis interval (P)
[Time Frame: Baseline through Month 12]
16.Mean inlet area under the curve (AUCinlet)
[Time Frame: Baseline through Month 12]
17.Mean outlet area under the curve (AUCoutlet)
[Time Frame: Baseline through Month 12]
18.Extraction ratio (ED)
[Time Frame: Baseline through Month 12]
19.Dialyzer blood flow (QD)
[Time Frame: Baseline through Month 12]
20.Cumulative amount excreted over all collection intervals (Ae0-T)
[Time Frame: Baseline through Month 12]
21.Fraction of the dose recovered after the last measurable time point postdose (Fe0-T)
[Time Frame: Baseline through Month 12]
22.Renal clearance (CLr)
[Time Frame: Baseline through Month 12]

+81-6-6210-8290

Oct. 12, 2022

No

USA/France/Spain/Australia