Fabry DiseasePhase 1NCT02930655
A Study to Assess the Safety and Tolerability of Lucerastat in Subjects With Fabry Disease
A Phase 1 study testing Lucerastat and Enzyme replacement therapy (ERT) in people with Fabry Disease, run by Idorsia Pharmaceuticals Ltd. at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fabry Disease
- What is being tested?
- Lucerastat and Enzyme replacement therapy (ERT)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteGermany
- Study dates
- 1 Feb 2015to 1 Feb 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Single-center, Open-label, Randomized, Versus a Control Group, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Oral Lucerastat in Adult Subjects With Fabry Disease Receiving Enzyme Replacement Therapy
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
- Being tested
- Lucerastat, Enzyme replacement therapy (ERT)
- Keywords
- Fabry disease, lucerastat
- Medical subject headings
- Fabry Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LucerastatDrug
Also called ACT-434964
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.
Enzyme replacement therapy (ERT)Drug
Also called Fabrazyme, Replagal
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: Drug: Enzyme replacement therapy (ERT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in blood pressure
Measured: Up to Week 12
Change from baseline in heart rate
Measured: 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
Measured: Up to Week 12
Change from baseline in body weight
Measured: Up to Week 12
Number of subjects with treatment-emergent adverse events and serious adverse events
Measured: Up to Week 12
Number of subjects with adverse events leading to premature discontinuation of lucerastat or ERT
Measured: Up to Week 12
Number of subjects with treatment-emergent abnormalities in laboratory variables
Measured: Up to Week 12
Secondary outcomes (10)
Change from baseline in plasma biomarkers of Fabry Disease
Biomarkers reflecting glycolipid metabolism were measured (unit of measure: ng/mL)
Measured: Up to Week 12
Change from baseline in urine biomarker of Fabry Disease
Biomarker reflecting glycolipid metabolism was measured (unit of measure: ng/mg)
Measured: Up to Week 12
Change from baseline in left ventricular ejection fraction (LVEF)
LVEF was used to monitor cardiac function in subjects with Fabry Disease
Measured: Up to Week 12
Change from baseline in left ventricular mass index (LVMi)
LVMi was used to monitor cardiac function in subjects with Fabry Disease
Measured: Up to Week 12
Change from baseline in estimated glomerular filtration rate (eGFR)
eGFR was used to monitor renal function in subjects with Fabry Disease
Measured: Up to Week 12
Change from baseline in urine albumin-to-creatinine ratio (UACR)
UACR was used to monitor renal function in subjects with Fabry Disease
Measured: Up to Week 12
Maximum plasma concentration (Cmax) of lucerastat
Cmax was determined directly from the observed plasma concentration-time curves of lucerastat. Blood samples for PK analyses were drawn at scheduled time points at the Week 4 visit
Measured: At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose
Time to reach Cmax (tmax) of lucerastat
tmax was determined directly from the observed plasma concentration-time curves of lucerastat. Blood samples for PK analyses were drawn at scheduled time points at the Week 4 visit
Measured: At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose
Area under the plasma concentration-time curve [AUC(tau)] of lucerastat
AUC(tau) corresponds to the area under the plasma concentration time curve of lucerastat over a dosing interval (tau = 12 hours)
Measured: At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose
Terminal half-life [t(1/2)]of lucerastat
Measured: At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2016 (estimated)
- Study start1 Feb 2015
- Primary completion1 Feb 2016
- Study completion1 Feb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nicolas Guérard, Study director, Actelion
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02930655
- Sponsor's protocol ID
- AC-069-104
- Status last verified
- Jul 2018
- First submitted
- 10 Oct 2016
- Last updated
- 10 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 28088251
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Open-label, Randomized, Versus a Control Group, Phase 1b Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Oral Lucerastat in Adult Subjects With Fabry Disease Receiving Enzyme Replacement Therapy
- ClinicalTrials.gov ID
- NCT02930655
- Acronym / sponsor ID
- AC-069-104
- Conditions
- Fabry Disease
- Keywords
- Fabry disease, lucerastat
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Idorsia Pharmaceuticals Ltd.Industry (pharma, biotech, devices)
- Study start
- 1 Feb 2015 (actual)
- Primary completion
- 1 Feb 2016 (actual)
- Study completion
- 1 Feb 2016 (actual)
- First posted
- 12 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Lucerastat group | Experimental | Drug: Lucerastat, Drug: Enzyme replacement therapy (ERT)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). |
| Control group | Experimental | Drug: Enzyme replacement therapy (ERT)Four subjects with Fabry Disease under enzyme replace therapy (ERT) as standard of care treatment were included as a control group. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LucerastatAlso: ACT-434964Hard 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. | Drug | Lucerastat group |
| Enzyme replacement therapy (ERT)Also: Fabrazyme, ReplagalAll 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. | Drug | Control group, Lucerastat group |
Primary outcome
Change from baseline in blood pressure
Time frame: Up to Week 12
Change from baseline in heart rate
Time frame: Up to Week 12
Change from baseline in electrocardiogram (ECG) variables
Time frame: Up to Week 12
The duration (in ms) of the different ECG variables were measured using a standard 12-lead ECG
Change from baseline in body weight
Time frame: Up to Week 12
Number of subjects with treatment-emergent adverse events and serious adverse events
Time frame: Up to Week 12
Number of subjects with adverse events leading to premature discontinuation of lucerastat or ERT
Time frame: Up to Week 12
Number of subjects with treatment-emergent abnormalities in laboratory variables
Time frame: Up to Week 12
10 secondary outcomes
Change from baseline in plasma biomarkers of Fabry Disease
Time frame: Up to Week 12
Change from baseline in urine biomarker of Fabry Disease
Time frame: Up to Week 12
Change from baseline in left ventricular ejection fraction (LVEF)
Time frame: Up to Week 12
Change from baseline in left ventricular mass index (LVMi)
Time frame: Up to Week 12
Change from baseline in estimated glomerular filtration rate (eGFR)
Time frame: Up to Week 12
Change from baseline in urine albumin-to-creatinine ratio (UACR)
Time frame: Up to Week 12
Maximum plasma concentration (Cmax) of lucerastat
Time frame: At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose
Time to reach Cmax (tmax) of lucerastat
Time frame: At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose
Area under the plasma concentration-time curve [AUC(tau)] of lucerastat
Time frame: At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose
Terminal half-life [t(1/2)]of lucerastat
Time frame: At Week 4 visit, blood samples drawn at the following time points: pre-dose, 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 6h, 8h, 10h, 12h post-dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2018.
- Derived from this study: PubMed 28088251Guerard 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicolas Guérard study director
Actelion
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lucerastat and Enzyme replacement therapy (ERT) in people with Fabry Disease, run by Idorsia Pharmaceuticals Ltd. at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in blood pressure (time frame: Up to Week 12). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02930655, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2018.