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

NCT02930655 | Completed Phase 1

• 1 other identifier: AC-069-104
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Fabry Disease

Keywords

Fabry disease; lucerastat

Outcome Measures

Primary Outcomes (7)

• Change from baseline in blood pressure

  Up to Week 12

• Change from baseline in heart rate

  Up to Week 12

• Change from baseline in electrocardiogram (ECG) variables

  The duration (in ms) of the different ECG variables were measured using a standard 12-lead ECG

  Up to Week 12

• Change from baseline in body weight

  Up to Week 12

• Number of subjects with treatment-emergent adverse events and serious adverse events

  Up to Week 12

• Number of subjects with adverse events leading to premature discontinuation of lucerastat or ERT

  Up to Week 12

• Number of subjects with treatment-emergent abnormalities in laboratory variables

  Up to Week 12

Secondary Outcomes (10)

• Change from baseline in plasma biomarkers of Fabry Disease

  Up to Week 12

• Change from baseline in urine biomarker of Fabry Disease

  Up to Week 12

• Change from baseline in left ventricular ejection fraction (LVEF)

  Up to Week 12

• Change from baseline in left ventricular mass index (LVMi)

  Up to Week 12

• Change from baseline in estimated glomerular filtration rate (eGFR)

  Up to Week 12

Study Arms (2)

Lucerastat group

EXPERIMENTAL

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).

Drug: Lucerastat; Drug: Enzyme replacement therapy (ERT)

Control group

EXPERIMENTAL

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

Drug: Enzyme replacement therapy (ERT)

Interventions

Lucerastat DRUG

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.

Also known as: ACT-434964

Lucerastat group

Enzyme replacement therapy (ERT) DRUG

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.

Also known as: Fabrazyme, Replagal

Control group; Lucerastat group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Idorsia Pharmaceuticals Ltd.: lead

Study Sites (1)

Investigator Site

Würzburg, 97080, Germany

Location

Related Publications (1)

• 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.

  PMID: 28088251 DERIVED

MeSH Terms

Conditions

Fabry Disease

Interventions

migalastat; Enzyme Replacement Therapy; agalsidase beta; agalsidase alfa

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

Enzyme Therapy; Drug Therapy; Therapeutics

Study Officials

• Nicolas Guérard

  Actelion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2016
• First Posted: October 12, 2016
• Study Start: February 1, 2015
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: July 10, 2018

Record last verified: 2018-07

Locations

DE (1)