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

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.