Efficacy and Safety of Lucerastat Oral Monotherapy in Adult Subjects With Fabry Disease (MODIFY)

• ClinicalTrials.gov Identifier: NCT03425539
• Recruitment Status: Completed
• First Posted: February 7, 2018
• Last Update Posted: August 9, 2022
• Sponsor: Idorsia Pharmaceuticals Ltd.
• Information provided by (Responsible Party): Idorsia Pharmaceuticals Ltd.

Tracking Information

• First Submitted Date: January 16, 2018
• First Posted Date: February 7, 2018
• Last Update Posted Date: August 9, 2022
• Actual Study Start Date: June 21, 2018
• Actual Primary Completion Date: August 17, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 17, 2020): Change from baseline to Month 6 in the "modified" Brief Pain Inventory-Short Form 3 (BPI-SF3) score of "neuropathic pain at its worst in the last 24 hours" [ Time Frame: From baseline to Month 6 (duration: 6 months) ]
• Original Primary Outcome Measures (submitted: February 1, 2018): Response to study treatment on neuropathic pain defined as a reduction from baseline to Month 6 of at least 30% in the "modified" BPI-SF3 score of "neuropathic pain at its worst in the last 24 hours" [ Time Frame: From baseline to Month 6 (duration: 6 months) ]

Current Secondary Outcome Measures (submitted: November 17, 2020)

• Change from baseline to Month 6 in the 11-point Numerical Rating Scale (NRS-11) score of "abdominal pain at its worst in the last 24 hours" in subjects with GI symptoms at baseline. [ Time Frame: From baseline to Month 6 (duration: 6 months) ]
• Change from baseline to Month 6 in the number of days with at least one stool of a Bristol Stool Scale (BSS) consistency Type 6 or 7 in subjects with GI symptoms at baseline. [ Time Frame: From baseline to Month 6 (duration: 6 months) ]
• Change from baseline to Month 6 in plasma globotriaosylceramide (Gb3). [ Time Frame: From baseline to Month 6 (duration: 6 months) ]

Original Secondary Outcome Measures (submitted: February 1, 2018)

• Change from baseline to Month 6 in the average daily 11-point Numerical Rating Scale (NRS-11) score of "abdominal pain at its worst in the last 24 hours" in subjects with GI symptoms at baseline. [ Time Frame: From baseline to Month 6 (duration: 6 months) ]
• Change from baseline to Month 6 in the number of days with at least one stool of a Bristol Stool Scale (BSS) consistency Type 6 or 7 in subjects with GI symptoms at baseline. [ Time Frame: From baseline to Month 6 (duration: 6 months) ]
• Change from baseline to Month 6 in plasma globotriaosylceramide (Gb3). [ Time Frame: From baseline to Month 6 (duration: 6 months) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of Lucerastat Oral Monotherapy in Adult Subjects With Fabry Disease
• Official Title: A Multicenter, dOuble-blind, ranDomized, Placebo-controlled, Parallel-group Study to Determine the effIcacy and Safety of Lucerastat Oral Monotherapy in Adult Subjects With FabrY Disease
• Brief Summary: This study aimed to determine the efficacy and safety of lucerastat oral monotherapy in adult subjects with Fabry disease.
• Detailed Description: The primary objective of this prospective, multicenter, double-blind, randomized, placebo-controlled, parallel group, Phase 3 study is to determine the effect of oral lucerastat monotherapy on neuropathic pain in subjects with Fabry disease (FD) through daily collection of patient-reported outcomes with an electronic diary.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Fabry Disease

Intervention

• Drug: Lucerastat
  Hard gelatin capsules containing 250 mg of lucerastat and inactive excipients; 1000 mg (4 capsules) twice daily (b.i.d.); dose adjusted for renal function.
• Drug: Placebo
  Placebo capsules are identical in appearance to the lucerastat capsules, and contain inactive excipients; 4 capsules b.i.d.; dose adjusted for renal function.

Study Arms

• Experimental: Lucerastat
  Intervention: Drug: Lucerastat
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 12, 2021): 182
• Original Estimated Enrollment (submitted: February 1, 2018): 108
• Actual Study Completion Date: September 2, 2021
• Actual Primary Completion Date: August 17, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Signed and dated ICF prior to any study-mandated procedure;
2. Male or female adult subjects;
3. FD diagnosis confirmed with local genetic test results;
4. Fabry-associated neuropathic pain, as defined by the subject, in the last 3 months prior to screening;

5. Enzyme replacement therapy (ERT) status:

   1. Subject never treated with ERT; or
   2. Subject has not received ERT for at least 6 months prior to screening; or
   3. Subject treated with ERT since at least 12 months at the time of the screening visit, and agreeing to stop ERT for approximately 8 months.
6. A woman of childbearing potential is eligible only under certain conditions, e.g. taking contraceptive measures.
7. Subjects with moderate or severe neuropathic pain during the screening period.

Exclusion Criteria:

1. Pregnant, planning to be become pregnant, or lactating subject.
2. Severe renal insufficiency (eGFR < 30 mL/min/1.73 m2) at screening.
3. Subject on regular dialysis for the treatment of chronic kidney disease.
4. Known and documented transient ischemic attack, stroke, unstable angina, or myocardial infarction within 6 months prior to screening.
5. Clinically significant unstable cardiac disease (e.g. uncontrolled symptomatic arrhythmia, congestive heart failure NYHA class III or IV).
6. Any known factor or disease that might interfere with treatment compliance, study conduct or interpretation of the results.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Canada, Germany, Ireland, Italy, Netherlands, Norway, Poland, Spain, Switzerland, United Kingdom, United States
• Removed Location Countries: Czechia, France

Administrative Information

• NCT Number: NCT03425539
• Other Study ID Numbers: ID-069A301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Idorsia Pharmaceuticals Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Idorsia Pharmaceuticals Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Idorsia Pharmaceuticals Ltd.

• PRS Account: Idorsia Pharmaceuticals Ltd.
• Verification Date: August 2022