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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amicus Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

19 Dec 2022 → ongoing

Decision date (initial)

2022-10-19

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Amicus Therapeutics Inc., USA

External identifiers

EU CT number

2022-500488-10-00

ClinicalTrials.gov

NCT04020055

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic

To characterize the pharmacokinetics (PK) of migalastat and confirm the proposed dosing regimens based on modeling and simulations in Fabry subjects with severe renal impairment (SRI) and end-stage renal disease (ESRD) on hemodialysis

Secondary objectives 3

1. To assess the safety of migalastat in subjects with Fabry disease and SRI and ESRD on hemodialysis
2. To assess the tolerability of migalastat in subjects with Fabry disease and SRI and ESRD on hemodialysis
3. To assess the pharmacodynamics (PD) of migalastat in subjects with Fabry disease and SRI or ESRD in support of adjusted dose regimens

Conditions and MedDRA coding

Fabry Disease and Amenable GLA Variants and Severe Renal Impairment or Endstage Renal Disease Treated with Hemodialysis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

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 (or assent) and authorization for use and disclosure of Personal Health Information or research-related health information or subject has a legally-authorized representative who has provided written informed consent and authorization, and subject provides assent, if applicable.
3. Subject has a GLA variant recorded in their medical records that is amenable to migalastat. • All subjects will have confirmatory GLA genotyping done at Visit 1. • For subjects without a known GLA variant, GLA genotyping results must be received prior to Visit 2. • For subjects with a GLA variant that has not yet been tested in the Migalastat Amenability Assay, amenability testing results must be received prior to Visit 2.
4. Subject has at least 1 documented eGFR value of < 30 mL/min/1.73 m2 in his/her medical history within the last 3 months and has an eGFRMDRD value of < 30 mL/min/1.73 m2 at Visit 1 per the central laboratory 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 (Visit 1).
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 subjects agree to use a medically accepted method of contraception during the study and for up to 30 days after the last dose of migalastat.

Exclusion criteria 13

1. Subject has undergone or is scheduled to undergo kidney transplantation.
2. Subject requires concurrent treatment with Zavesca® (miglustat) or has been treated with Zavesca within the 30 days before Visit 1.
3. Female subject is pregnant or breastfeeding.
4. Subject is unable to comply with study requirements, or deemed otherwise unsuitable for study entry, in the opinion of the investigator.
5. Subject is on peritoneal dialysis.
6. Subject is treated or has been treated with another investigational drug (except migalastat) within the 30 days before Visit 1.
7. Subject has undergone any gene therapy at any time prior to the study or anticipates undergoing gene therapy during the study.
8. Subject has had a documented transient ischemic attack, stroke, unstable angina, or myocardial infarction within the 3 months before Visit 1.
9. Subject has clinically significant unstable cardiac disease in the opinion of the investigator (eg, cardiac disease requiring active management, such as symptomatic arrhythmia, unstable angina, or New York Heart Association Class III or IV congestive heart failure).
10. Subject has any intercurrent illness or condition that may preclude the subject from fulfilling the protocol requirements or suggests to the investigator that the potential subject may have an unacceptable risk by participating in this study.
11. Subject has a history of allergy or sensitivity to migalastat (including excipients) or other iminosugars (eg, miglustat, miglitol).
12. Subject requires concurrent treatment with Glyset® (miglitol), Replagal® (agalsidase alfa), or Fabrazyme® (agalsidase beta) or has been treated with these medications within 14 days before Visit 2.
13. In France only, protected persons as defined by the Public Health Code.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Pharmacokinetic parameters and dosing confirmation will be estimated based on concentrations of migalastat in plasma and urine

Secondary endpoints 3

1. Safety endpoints will include: adverse events, clinical laboratory parameters (serum chemistry, hematology, and urinalysis), eGFRMDRD and eGFRCKD-EPI, vital signs (blood pressure, HR, RR, and body temperature), 12-lead ECGs, physical examinations
2. Tolerability endpoints will include: treatment-emergent adverse events (incidence of SAEs, discontinuation due to AE, and severity of TEAE)
3. PD endpoint will include change from baseline in plasma lyso-Gb3

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amicus Therapeutics Inc.

Sponsor organisation

Amicus Therapeutics Inc.

Address

47 Hulfish Street

City

Princeton

Postcode

08542-3713

Country

United States

Scientific contact point

Organisation

Amicus Therapeutics Inc.

Contact name

Haichen Yang

Public contact point

Organisation

Amicus Therapeutics Inc.

Contact name

Amicus Patient Advocacy

Third parties 7

Locations

3 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 25 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications