Principal Investigator: Nicola Longo
Keywords: Fabry , Lucerastat Department: Pediatric Genetics
IRB Number: 00111681
Specialty: Pediatric Genetics
Sub Specialties: Medical Genetics
Recruitment Status: Not yet recruiting

Contact Information

Carrie Bailey
carrie.bailey@hsc.utah.edu
8015873605

Brief Summary

Primary objective
The primary objective of the study is to determine the effect of lucerastat on neuropathic
pain in subjects with Fabry Disease.

Secondary objectives
• To determine the effects of lucerastat on GI symptoms (abdominal pain and diarrhea)
in subjects with FD and GI symptom(s) at baseline
• To confirm the effect of lucerastat on biomarkers of Fabry Disease
• To determine the safety and tolerability of lucerastat in subjects with Fabry Disease

Other objectives
• To evaluate the effect of lucerastat on renal function and cardiac parameters in
subjects with Fabry Disease
• To evaluate the effect of lucerastat on depression in subjects with Fabry Disease 

• To evaluate the effect of lucerastat on QoL in subjects with FD;
• To document the PK of lucerastat in subjects with FD.

Inclusion Criteria

1. Signed and dated ICF prior to any study-mandated procedure;
2. Male or female subjects; 18 -years old and above;
3. FD diagnosis confirmed with local genetic test results (i.e., presence of at least 1 mutation in GLA, the gene coding for α-GalA);
4. Fabry-associated neuropathic pain, as defined by the subject, in the last 3 months prior to screening;
5. ERT treatment status:
a) Subject never treated with ERT; or
b) Subject has not received ERT for at least 6 months prior to screening; or
c) Subject treated with ERT at the time of the screening visit, and meeting all of the following criteria at the time of screening:
i) ERT administration for the last 12 months;
ii) Stable ERT dose regimen during the last 3 months;
iii) Subject agrees to stop ERT administration at the screening visit for approximately 8 months (6–7 weeks screening + 6 months of double-blind treatment).
6. A woman of childbearing potential is eligible only if the following applies:
• Negative serum pregnancy test at screening and a negative urine pregnancy test at randomization;
• Agreement to undertake monthly urine pregnancy tests during the study and up to at least 30 days after study treatment discontinuation;
• Agreement to follow a highly effective contraception scheme from screening up to at least 30 days after study treatment discontinuation.
7. A fertile male (physiologically capable of conceiving a child according to investigator judgment) who is sexually active with a woman of childbearing potential is eligible only if the following applies:                        – Agreement to use a condom during the treatment period (starting at randomization) and for up to 3 months after study treatment discontinuation; and
          – Agreement to not to father a child during this period.                                                                 

8. Adequate subject compliance with completion of an eDiary during the screening period;
9. Subjects with moderate or severe neuropathic pain as determined from daily entries of the modified Brief Pain Inventory-Short Form item 3 (BPI-SF3) score of “neuropathic pain at its worst in the last 24 hours” in the eDiary during the screening period.
 

Exclusion Criteria

1. Pregnant / planning to become pregnant up to 30 days after study treatment discontinuation or lactating subject;

2. Severe renal insufficiency defined as an estimated glomerular filtration rate (eGFR) per the Chronic Kidney Disease Epidemiology Collaboration creatinine equation < 30 mL/min/1.73 m2 at screening (as reported by the central laboratory);

3. Subject on regular dialysis for the treatment of chronic kidney disease;

4. Subject has undergone, or is on a waiting list for, or is scheduled to undergo kidney or other organ transplantation.

5. Known and documented transient ischemic attack, stroke, unstable angina or myocardial infarction within 6 months prior to screening;

6. Clinically significant unstable cardiac disease in the opinion of the investigator (e.g., uncontrolled symptomatic arrhythmia, New York Heart Association class III or IV congestive heart failure);

7. Any other subject at high risk of developing clinical signs of organ involvement within the time period of the study, as per investigator judgment;                                                                                                         

8. Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as:
a) Other disease or condition associated with a pain component that could confound assessment of neuropathic pain (e.g., diabetic neuropathy, chemotherapy- or radiation-induced peripheral neuropathy, chronic inflammatory demyelinating polyneuropathy);
b) Other disease of the GI tract that could interfere with the assessment of GI symptoms in FD (e.g., inflammatory bowel disease);
c) Documented poorly controlled diabetes mellitus (i.e., HbA1c > 8.0% at screening as reported by the central laboratory);
d) Significant neurological disorder;
e) Significant psychiatric disease; suicidal ideation at screening or history of suicide attempt or behavior within 6 months prior to screening as per investigator judgment;
f) History of drug dependence (including opioids) or alcohol dependence;
g) Inability to complete an eDiary on a daily basis.

9. Known concomitant life-threatening disease with a life expectancy < 18 months;

10. Subject planned for imminent initiation of treatment with ERT;

11. Known hypersensitivity to lucerastat or drug of the same chemical class of iminosugars (e.g., miglitol, miglustat, migalastat), or any of their excipients;

12. Initiation or treatment at an unstable dose within 4 weeks prior to screening with any of the following medications:
a) Angiotensin-converting enzyme (ACE) inhibitor and/or angiotensin receptor blocker (ARB);
b) Anti-epileptic;                                                                                                                             

c) Tricyclic antidepressant (TCA) and/or other antidepressants belonging to the serotonin-norepinephrine re-uptake inhibitor (SNRI) and selective serotonin re-uptake inhibitor (SSRI) classes.

13. Planned or current treatment with another investigational treatment within 3 months prior to screening;

14. Treatment with any inhibitor of the glucosylceramide synthase (GCS) (e.g., miglustat, lucerastat, eliglustat, ibiglustat/venglustat) or an α-GalA chaperone (e.g., migalastat) within 6 months prior to screening;

15.Treatment with ERT (agalsidase alfa, agalsidase beta) during the screening period.