Primary objectiveThe primary objective of the study is to determine the long term safety and tolerability of lucerastat in subjects with Fabry disease (FD).Secondary objectives* To evaluate the effect of lucerastat on renal function and cardiac…
ID
Source
Brief title
Condition
- Congenital and hereditary disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety endpoints
* Treatment-emergent adverse events (AEs) and serious AEs (SAEs) up to FU1
visit;
* AEs leading to premature discontinuation of study treatment;
* Change from baseline to each visit up to Month 48 in vital signs;
* Change from baseline to each visit up to Month 24 in 12 lead
electrocardiogram (ECG) variables;
* Treatment-emergent marked abnormalities for quantitative 12 lead ECG
variables at each visit up to Month 24;
* Change from baseline to each visit up to Month 48 in laboratory variables
[see list in Section 7.2.4.2 of the protocol];
* Treatment-emergent marked abnormalities for selected laboratory variables at
each visit up to Month 48.
Main efficacy endpoints
* Subject eGFR slope from baseline to Month 24 and from baseline to Month 48;
* Change from baseline to Month 24 in left ventricular mass index (LVMI) as
measured by echocardiography;
* Change from baseline to Month 24 and Month 48 in plasma globotriaosylceramide
(Gb3).
Secondary outcome
Other efficacy endpoints
Other efficacy endpoints are described in Section 6.2.2.
Other endpoints (quality of life, other biomarkers)
Other endpoints are described in Sections 6.3 and 6.4.
Background summary
See protocol chapter 1 "Background" p. 29-37.
Study objective
Primary objective
The primary objective of the study is to determine the long term safety and
tolerability of lucerastat in subjects with Fabry disease (FD).
Secondary objectives
* To evaluate the effect of lucerastat on renal function and cardiac parameters
in subjects with FD;
* To evaluate the long-term effect of lucerastat on biomarkers of FD.
Other objectives
Other objectives are described in Section 2.3 and 6 of the protocol.
Study design
This is a prospective, multi-center, open-label, uncontrolled, single-arm,
extension Phase 3 study.
Up to approximately 108 adult subjects with FD who completed the 6-month,
double-blind treatment period in study ID-069A301 will be enrolled to receive
lucerastat for approximately 48 months.
The study comprises the following consecutive periods:
Treatment period: Lasts about 48 months. These 48 months are split into part 1
and part 2. Part 1 begins with the signing of the informed consent form (during
visit 1 day 1) and ends at the end of month 24. Then the patient will be asked
if he/she wants to participate in part 2 of the study. This starts with the
last visit of part 1, and ends with the EOT visit after a total of 48 months
Post-treatment safety follow-up (FU) period: The FU period is applicable to all
subjects. It starts on the day after the last dose of study treatment:
* For female and non-fertile male subjects it includes 1 safety FU telephone
call (FU1) taking place approximately 1 month after the last dose of study
treatment.
* For fertile male subjects it includes 2 safety FU telephone calls taking
place approximately 1 month (FU1) and 3 months (FU2) after the last dose of
study treatment.
In addition, any male subject who requires repeated male reproductive safety
assessments will return at the time of the FU2 visit to the site and/or
qualified local facility to perform those assessments as described in Sections
7.2.4.2.1 and 7.2.4.2.4. Subjects who discontinue study treatment prematurely
for any reason should be subsequently treated according to local
standard-of-care at the investigator*s discretion.
Intervention
Lucerastat is available for clinical study use in hard gelatin capsules
containing 250 mg of lucerastat and inactive excipients (lactose anhydrous and
talc).
The starting dose of the study treatment (lucerastat) will be based on the
subject*s last available eGFR value, as reported in study ID-069A301 by the
central laboratory [see Table 1].
During the study, the dose of the study treatment will be adjusted based on
subject*s eGFR (as reported by the central laboratory during scheduled or
unscheduled visits). The following rules apply:
a. Subject*s eGFR decreases and crosses the next lower eGFR boundary:
Upon receipt of the eGFR results from the central laboratory, the
investigator/delegate will contact the subject to provide instruction to reduce
the dose as needed. The date of the contact with the subject and the adjusted
dose will be collected in the electronic case report form (eCRF).
b. Subject*s eGFR increases and crosses the next upper eGFR boundary:
Dose adjustment must not be performed until the eGFR increase is confirmed by a
second central laboratory test (during scheduled or unscheduled visits
performed at least 3 months after the first test). Upon receipt of the second
laboratory results confirming the increase and boundary cross, the
investigator/delegate will contact the subject to provide instruction to
increase the dose as needed. The date of the contact with the subject and the
adjusted dose will be collected in the eCRF.
Study treatment must be discontinued if one of the study treatment stopping
criteria is met (see Section 5.1.8).
Study burden and risks
The following adverse reactionsside effects have been observed with treatment
with lucerastatseen with lucerastat in 4 or more subjects (out of 80 subjects):
* Abdominal complaints side effects (gastrointestinal complaintsside effects):
-nausea (11 persons, 14%)
* -diarrhoea, soft stools (9 persons, 11%)
-flatulence (gas development in intestines) (7 persons, 9%)
-vomiting (6 people, 8%)
-stomach pain (4 people, 5%)
-dry mouth (4 people, 5%)
* Other side effects were:
-headache (9 persons, 11%)
-itchy skin (6 persons, 8%)
-joint pain (5 persons, 6%)
-back pain (5 persons, 6%)
-vaccination complications (5 persons, 6%)
Blood draws: discomfort when inserting the needle. Taking blood with a needle
can cause some pain and bruising
cause spots on the arm.
Hegenheimermattweg 91
Allschwil 4123
CH
Hegenheimermattweg 91
Allschwil 4123
CH
Listed location countries
Age
Inclusion criteria
1. Signed and dated ICF prior to any study-mandated procedure;
2. Subject completed the 6-month, double-blind treatment period in study ID
069A301.
Exclusion criteria
1. Pregnant / planning to become pregnant or lactating subject;
2. Subject considered to be at high risk of developing clinical signs of organ
involvement within the time period of the study, as per investigator judgment;
3. Any known factor or disease that might interfere with treatment compliance,
study conduct or interpretation of the results as per investigator judgment.,
In addition, the subject must not be enrolled in study ID-069A302 if at any
time during study ID-069A301, one of the following criteria was met:
4. Subject*s eGFR per the Chronic Kidney Disease Epidemiology Collaboration
creatinine equation < 15 mL/min/1.73 m2;
5. Subject experienced an event of acute kidney injury Common Terminology
Criteria for Adverse Event (CTCAE) grade 2 or above;
6. Subject experienced an event of stroke CTCAE grade 3 or above;
7. Subject experienced an event of heart failure leading to in-patient
hospitalization or prolongation of ongoing hospitalization.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-002210-12-NL |
| ClinicalTrials.gov | NCT03425539 |
| CCMO | NL67016.018.18 |