Trial Outcomes & Findings for Efficacy and Safety of Lucerastat Oral Monotherapy in Adult Subjects With Fabry Disease (NCT NCT03425539)

Last Updated: 2024-08-09

Results Overview

Neuropathic pain on the modified BPI-SF3: subjects rated their neuropathic pain intensity ("neuropathic pain at its worst in the last 24 hours") on an 11-point scale, from 0 (no neuropathic pain) to 10 (worst imaginable neuropathic pain).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

118 participants

Primary outcome timeframe

From baseline to Month 6 (duration: 6 months)

Results posted on

2024-08-09

Participant Flow

The study was conducted at 49 sites in 14 countries, including North America (USA, CAN), Europe (Austria, Belgium, Germany, Ireland, Italy, Netherlands, Norway, Poland, Spain, Switzerland, UK), and Australia.

Participant milestones

Participant milestones
Measure	Lucerastat Lucerastat (ACT-434964) was provided as hard-gelatin capsules containing 250 mg of lucerastat. Capsules were administered orally twice daily (b.i.d.) to provide a lucerastat dose of 250, 500, 750, or 1000 mg b.i.d. based on the subject's estimated glomerular filtration rate (eGFR).	Placebo Matching placebo capsules were administered orally b.i.d., with the number of capsules administered based on the subject's eGFR.
Overall Study STARTED	80	38
Overall Study Treated	80	37
Overall Study COMPLETED	75	34
Overall Study NOT COMPLETED	5	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Lucerastat Lucerastat (ACT-434964) was provided as hard-gelatin capsules containing 250 mg of lucerastat. Capsules were administered orally twice daily (b.i.d.) to provide a lucerastat dose of 250, 500, 750, or 1000 mg b.i.d. based on the subject's estimated glomerular filtration rate (eGFR).	Placebo Matching placebo capsules were administered orally b.i.d., with the number of capsules administered based on the subject's eGFR.
Overall Study Randomized but not treated	0	1
Overall Study Adverse Event	2	2
Overall Study Withdrawal by Subject	3	0
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lucerastat n=80 Participants Lucerastat (ACT-434964) was provided as hard-gelatin capsules containing 250 mg of lucerastat. Capsules were administered orally b.i.d. to provide a lucerastat dose of 250, 500, 750, or 1000 mg b.i.d. based on the subject's eGFR.	Placebo n=38 Participants Matching placebo capsules were administered orally b.i.d., with the number of capsules administered based on the subject's eGFR.	Total n=118 Participants Total of all reporting groups
Age, Continuous	38 years n=5 Participants	39 years n=7 Participants	39 years n=5 Participants
Sex: Female, Male Female	43 Participants n=5 Participants	20 Participants n=7 Participants	63 Participants n=5 Participants
Sex: Female, Male Male	37 Participants n=5 Participants	18 Participants n=7 Participants	55 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	76 Participants n=5 Participants	37 Participants n=7 Participants	113 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants	6 participants n=7 Participants	32 participants n=5 Participants
Region of Enrollment United Kingdom	8 participants n=5 Participants	3 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment Switzerland	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Spain	7 participants n=5 Participants	6 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment Canada	10 participants n=5 Participants	5 participants n=7 Participants	15 participants n=5 Participants
Region of Enrollment Netherlands	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Austria	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment Belgium	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Norway	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Region of Enrollment Poland	9 participants n=5 Participants	4 participants n=7 Participants	13 participants n=5 Participants
Region of Enrollment Australia	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment Germany	10 participants n=5 Participants	4 participants n=7 Participants	14 participants n=5 Participants
Neuropathic pain monthly score at baseline	6.26 units on a scale STANDARD_DEVIATION 1.54 • n=5 Participants	6.11 units on a scale STANDARD_DEVIATION 1.39 • n=7 Participants	6.21 units on a scale STANDARD_DEVIATION 1.49 • n=5 Participants

PRIMARY outcome

Timeframe: From baseline to Month 6 (duration: 6 months)

Population: The analysis included all subjects who were randomized and took at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Lucerastat n=80 Participants Lucerastat (ACT-434964) was provided as hard-gelatin capsules containing 250 mg of lucerastat. Capsules were administered orally b.i.d. to provide a lucerastat dose of 250, 500, 750, or 1000 mg b.i.d. based on the subject's eGFR.	Placebo n=37 Participants Matching placebo capsules were administered orally b.i.d., with the number of capsules administered based on the subject's eGFR.
Neuropathic Pain Monthly Score: Change From Baseline to Month 6	-1.64 score on a scale Interval -2.11 to -1.16	-2.05 score on a scale Interval -2.73 to -1.37

SECONDARY outcome

Timeframe: From baseline to Month 6 (duration: 6 months)

Population: The analysis included all subjects who were randomized and took at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Lucerastat n=80 Participants Lucerastat (ACT-434964) was provided as hard-gelatin capsules containing 250 mg of lucerastat. Capsules were administered orally b.i.d. to provide a lucerastat dose of 250, 500, 750, or 1000 mg b.i.d. based on the subject's eGFR.	Placebo n=37 Participants Matching placebo capsules were administered orally b.i.d., with the number of capsules administered based on the subject's eGFR.
Plasma Globotriaosylceramide (Gb3; in ng/ml): Change From Baseline to Month 6	-672.68 ng/ml Interval -798.91 to -546.46	200.84 ng/ml Interval 14.29 to 387.4

SECONDARY outcome

Timeframe: From baseline to Month 6 (duration: 6 months)

Population: The analysis included randomized and treated subjects with gastrointestinal symptoms at baseline (diarrhea on at least 8 days and/or moderate or severe abdominal pain in the 4 weeks prior to randomization).

Abdominal pain on the 11-point Numerical Rating Scale (NRS-11): subjects rated their abdominal pain intensity ("abdominal pain at its worst in the last 24 hours") on an 11-point scale, from 0 (no pain) to 10 (worst imaginable pain).

Outcome measures

Outcome measures
Measure	Lucerastat n=61 Participants Lucerastat (ACT-434964) was provided as hard-gelatin capsules containing 250 mg of lucerastat. Capsules were administered orally b.i.d. to provide a lucerastat dose of 250, 500, 750, or 1000 mg b.i.d. based on the subject's eGFR.	Placebo n=29 Participants Matching placebo capsules were administered orally b.i.d., with the number of capsules administered based on the subject's eGFR.
Abdominal Pain Monthly Score: Change From Baseline to Month 6	-1.37 score on a scale Interval -1.86 to -0.87	-1.68 score on a scale Interval -2.38 to -0.98

SECONDARY outcome

Timeframe: From baseline to Month 6 (duration: 6 months)

A subject was considered to have diarrhea on a specific day if at least one stool of a Bristol Stool Scale (BSS) consistency Type 6 or 7 was reported. The number of days with diarrhea at baseline and Month 6 was the number of days with diarrhea over the 4 weeks prior to the randomization visit or the Month 6 visit, respectively, adjusted for the number of days with data available.

Outcome measures

Outcome measures
Measure	Lucerastat n=48 Participants Lucerastat (ACT-434964) was provided as hard-gelatin capsules containing 250 mg of lucerastat. Capsules were administered orally b.i.d. to provide a lucerastat dose of 250, 500, 750, or 1000 mg b.i.d. based on the subject's eGFR.	Placebo n=25 Participants Matching placebo capsules were administered orally b.i.d., with the number of capsules administered based on the subject's eGFR.
Number of Days With Diarrhea: Change From Baseline to Month 6	-3.45 Number of days within 4 weeks Standard Deviation 4.96	-3.95 Number of days within 4 weeks Standard Deviation 9.29

Adverse Events

Lucerastat

Serious events: 5 serious events

Other events: 46 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Lucerastat n=80 participants at risk Lucerastat (ACT-434964) was provided as hard-gelatin capsules containing 250 mg of lucerastat. Capsules were administered orally b.i.d. to provide a lucerastat dose of 250, 500, 750, or 1000 mg b.i.d. based on the subject's eGFR.	Placebo n=37 participants at risk Matching placebo capsules were administered orally b.i.d., with the number of capsules administered based on the subject's eGFR.
Cardiac disorders Ventricular tachycardia	1.2% 1/80 • Number of events 1 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.	0.00% 0/37 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.
Ear and labyrinth disorders Vertigo positional	1.2% 1/80 • Number of events 1 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.	0.00% 0/37 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.
General disorders Drug withdrawal syndrome	1.2% 1/80 • Number of events 1 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.	0.00% 0/37 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.
Infections and infestations Hepatitis viral	1.2% 1/80 • Number of events 1 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.	0.00% 0/37 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.
Infections and infestations Localised infection	1.2% 1/80 • Number of events 1 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.	0.00% 0/37 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.
Infections and infestations Septic encephalopathy	1.2% 1/80 • Number of events 1 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.	0.00% 0/37 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.
Infections and infestations Streptococcal bacteraemia	1.2% 1/80 • Number of events 1 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.	0.00% 0/37 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.
Infections and infestations Tooth abscess	0.00% 0/80 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.	2.7% 1/37 • Number of events 1 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.
Nervous system disorders Ischaemic stroke	1.2% 1/80 • Number of events 1 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.	0.00% 0/37 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.2% 1/80 • Number of events 1 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.	0.00% 0/37 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.
Surgical and medical procedures Implantable defibrillator insertion	1.2% 1/80 • Number of events 1 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.	0.00% 0/37 • Treatment-emergent adverse events from the 6-month treatment period are reported. Adverse events were considered treatment-emergent if the onset date was between the first intake of study treatment up to 30 days after the end of study treatment. Adverse events for all subjects in the lucerastat arm are reported together, regardless of dose. This is due to the study treatment dosing scheme, where each subject's dose of study treatment was based on their individual eGFR.

Other adverse events

Additional Information

Idorsia Clinical Trial Information

Idorsia Pharmaceuticals Ltd

Phone: +1 856 661 3721

Email: [email protected]

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