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A Study to Assess the Safety and Tolerability of Lucerastat in Subjects With Fabry Disease

Primary Purpose

Fabry Disease

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Lucerastat
Enzyme replacement therapy (ERT)
Sponsored by
Idorsia Pharmaceuticals Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Fabry Disease focused on measuring Fabry disease, lucerastat

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Signed informed consent form
  • Male and female adult subjects with a diagnosis of Fabry Disease (FD) based on historical assessments (residual α-GAL A activity level below lower limit of normal for males and presence of a galactosidase alpha mutation for females) and a history of clinical symptoms of FD
  • On ERT for at least 24 months without any change in dose within the last 6 months prior to screening

Exclusion Criteria:

  • Severe renal function impairment
  • Severe residual neurologic deficit
  • Clinically significant unstable cardiac disease
  • Any circumstances or conditions, which, in the opinion of the investigator, may have affected full participation in the study or compliance with the protocol

Sites / Locations

  • Investigator Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Lucerastat group

Control group

Arm Description

Ten subjects with Fabry Disease received 1000 mg of oral lucerastat twice daily for 12 weeks in addition to their standard of care treatment (enzyme replace therapy).

Four subjects with Fabry Disease under enzyme replace therapy (ERT) as standard of care treatment were included as a control group.

Outcomes

Primary Outcome Measures

Change from baseline in blood pressure
Change from baseline in heart rate
Change from baseline in electrocardiogram (ECG) variables
The duration (in ms) of the different ECG variables were measured using a standard 12-lead ECG
Change from baseline in body weight
Number of subjects with treatment-emergent adverse events and serious adverse events
Number of subjects with adverse events leading to premature discontinuation of lucerastat or ERT
Number of subjects with treatment-emergent abnormalities in laboratory variables

Secondary Outcome Measures

Change from baseline in plasma biomarkers of Fabry Disease
Biomarkers reflecting glycolipid metabolism were measured (unit of measure: ng/mL)
Change from baseline in urine biomarker of Fabry Disease
Biomarker reflecting glycolipid metabolism was measured (unit of measure: ng/mg)
Change from baseline in left ventricular ejection fraction (LVEF)
LVEF was used to monitor cardiac function in subjects with Fabry Disease
Change from baseline in left ventricular mass index (LVMi)
LVMi was used to monitor cardiac function in subjects with Fabry Disease
Change from baseline in estimated glomerular filtration rate (eGFR)
eGFR was used to monitor renal function in subjects with Fabry Disease
Change from baseline in urine albumin-to-creatinine ratio (UACR)
UACR was used to monitor renal function in subjects with Fabry Disease
Maximum plasma concentration (Cmax) of lucerastat
Cmax was determined directly from the observed plasma concentration-time curves of lucerastat. Blood samples for PK analyses were drawn at scheduled time points at the Week 4 visit
Time to reach Cmax (tmax) of lucerastat
tmax was determined directly from the observed plasma concentration-time curves of lucerastat. Blood samples for PK analyses were drawn at scheduled time points at the Week 4 visit
Area under the plasma concentration-time curve [AUC(tau)] of lucerastat
AUC(tau) corresponds to the area under the plasma concentration time curve of lucerastat over a dosing interval (tau = 12 hours)
Terminal half-life [t(1/2)]of lucerastat

Full Information

First Posted
October 10, 2016
Last Updated
July 6, 2018
Sponsor
Idorsia Pharmaceuticals Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT02930655
Brief Title
A Study to Assess the Safety and Tolerability of Lucerastat in Subjects With Fabry Disease
Official Title
A Single-center, Open-label, Randomized, Versus a Control Group, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Oral Lucerastat in Adult Subjects With Fabry Disease Receiving Enzyme Replacement Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
February 1, 2015 (Actual)
Primary Completion Date
February 1, 2016 (Actual)
Study Completion Date
February 1, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Idorsia Pharmaceuticals Ltd.

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary purpose of this study was to assess the safety and tolerability of lucerastat in adults with Fabry Disease receiving Enzyme Replacement Therapy (ERT). The secondary objectives were to investigate the effects of lucerastat on plasma and urine levels of biomarkers, to assess its effects on renal and cardiac functions and to determine the pharmacokinetic profile of lucerastat at steady-state.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fabry Disease
Keywords
Fabry disease, lucerastat

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lucerastat group
Arm Type
Experimental
Arm Description
Ten subjects with Fabry Disease received 1000 mg of oral lucerastat twice daily for 12 weeks in addition to their standard of care treatment (enzyme replace therapy).
Arm Title
Control group
Arm Type
Experimental
Arm Description
Four subjects with Fabry Disease under enzyme replace therapy (ERT) as standard of care treatment were included as a control group.
Intervention Type
Drug
Intervention Name(s)
Lucerastat
Other Intervention Name(s)
ACT-434964
Intervention Description
Hard gelatin capsules for oral administration formulated at a strength of 250 mg, and administered as 4 capsules in the morning and 4 capsules in the evening.
Intervention Type
Drug
Intervention Name(s)
Enzyme replacement therapy (ERT)
Other Intervention Name(s)
Fabrazyme, Replagal
Intervention Description
All the subjects received an ERT as background therapy for at least 24 months prior to the screening visit and they had to continue receiving this treatment during the conduct of the study.
Primary Outcome Measure Information:
Title
Change from baseline in blood pressure
Time Frame
Up to Week 12
Title
Change from baseline in heart rate
Time Frame
Up to Week 12
Title
Change from baseline in electrocardiogram (ECG) variables
Description
The duration (in ms) of the different ECG variables were measured using a standard 12-lead ECG
Time Frame
Up to Week 12
Title
Change from baseline in body weight
Time Frame
Up to Week 12
Title
Number of subjects with treatment-emergent adverse events and serious adverse events
Time Frame
Up to Week 12
Title
Number of subjects with adverse events leading to premature discontinuation of lucerastat or ERT
Time Frame
Up to Week 12
Title
Number of subjects with treatment-emergent abnormalities in laboratory variables
Time Frame
Up to Week 12
Secondary Outcome Measure Information:
Title
Change from baseline in plasma biomarkers of Fabry Disease
Description
Biomarkers reflecting glycolipid metabolism were measured (unit of measure: ng/mL)
Time Frame
Up to Week 12
Title
Change from baseline in urine biomarker of Fabry Disease
Description
Biomarker reflecting glycolipid metabolism was measured (unit of measure: ng/mg)
Time Frame
Up to Week 12
Title
Change from baseline in left ventricular ejection fraction (LVEF)
Description
LVEF was used to monitor cardiac function in subjects with Fabry Disease
Time Frame
Up to Week 12
Title
Change from baseline in left ventricular mass index (LVMi)
Description
LVMi was used to monitor cardiac function in subjects with Fabry Disease
Time Frame
Up to Week 12
Title
Change from baseline in estimated glomerular filtration rate (eGFR)
Description
eGFR was used to monitor renal function in subjects with Fabry Disease
Time Frame
Up to Week 12
Title
Change from baseline in urine albumin-to-creatinine ratio (UACR)
Description
UACR was used to monitor renal function in subjects with Fabry Disease
Time Frame
Up to Week 12
Title
Maximum plasma concentration (Cmax) of lucerastat
Description
Cmax was determined directly from the observed plasma concentration-time curves of lucerastat. Blood samples for PK analyses were drawn at scheduled time points at the Week 4 visit
Time Frame
At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose
Title
Time to reach Cmax (tmax) of lucerastat
Description
tmax was determined directly from the observed plasma concentration-time curves of lucerastat. Blood samples for PK analyses were drawn at scheduled time points at the Week 4 visit
Time Frame
At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose
Title
Area under the plasma concentration-time curve [AUC(tau)] of lucerastat
Description
AUC(tau) corresponds to the area under the plasma concentration time curve of lucerastat over a dosing interval (tau = 12 hours)
Time Frame
At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose
Title
Terminal half-life [t(1/2)]of lucerastat
Time Frame
At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent form Male and female adult subjects with a diagnosis of Fabry Disease (FD) based on historical assessments (residual α-GAL A activity level below lower limit of normal for males and presence of a galactosidase alpha mutation for females) and a history of clinical symptoms of FD On ERT for at least 24 months without any change in dose within the last 6 months prior to screening Exclusion Criteria: Severe renal function impairment Severe residual neurologic deficit Clinically significant unstable cardiac disease Any circumstances or conditions, which, in the opinion of the investigator, may have affected full participation in the study or compliance with the protocol
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicolas Guérard
Organizational Affiliation
Actelion
Official's Role
Study Director
Facility Information:
Facility Name
Investigator Site
City
Würzburg
ZIP/Postal Code
97080
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
28088251
Citation
Guerard N, Morand O, Dingemanse J. Lucerastat, an iminosugar with potential as substrate reduction therapy for glycolipid storage disorders: safety, tolerability, and pharmacokinetics in healthy subjects. Orphanet J Rare Dis. 2017 Jan 14;12(1):9. doi: 10.1186/s13023-017-0565-9.
Results Reference
derived

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A Study to Assess the Safety and Tolerability of Lucerastat in Subjects With Fabry Disease

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