Primary objective:To evaluate the efficacy of soraprazan in reducing the amount of lipofuscin inRPE cells of subjects with Stargardt disease by assessing the change inquantitative auto-fluorescence (qAF8) from baseline to after treatment…
ID
Source
Brief title
Condition
- Retina, choroid and vitreous haemorrhages and vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in qAF8 score from baseline to end of treatment (EoT) for soraprazan
compared to placebo treated subjects. Evaluation of qAF8 score for all subjects
will be done at a central reading centre.
Secondary outcome
Functional
1. Best-corrected visual acuity (BCVA) as measured by Early
Treatment Diabetic Retinopathy Study (ETDRS) charts
2. BCVA as measured by ETDRS chart under low luminance
conditions (LLVA)
3. Low Luminance Deficit (LLD) calculated as the difference between
BCVA and LLVA
4. Change from baseline in binocular and monocular maximum
reading speed as assessed by Radner Charts
5. Change from baseline in binocular and monocular critical print size
as assessed by Radner charts.
6. Macular functional response as assessed by mesopic
microperimetry
7. Subject-reported visual function as assessed by the National Eye
Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) and
Functional Reading Independence (FRI) Index
Structural
8. Changes in central subfield retinal thickness (CSRT) as assessed
by spectral-domain optical coherence tomography (SD-OCT)
9. Changes in macular volume as assessed by SD-OCT
10. Changes in outer nuclear layer (ONL) thickness as assessed by
SD-OCT
11. Changes in Ellipsoid Zones (EZ) as assessed by SD-OCT
12. Presence and changes of macular atrophy by fundus
autofluorescence
13. Lesion progression
Background summary
Stargardt disease (STGD) is an orphan indication and genetic eye disorder that
causes progressive vision loss. Individuals with the condition have abnormal
accumulation of fatty yellow pigment (lipofuscin) in the cells of the retinal
pigment epithelium (RPE) underlying the macula. Lipofuscin is auto-fluorescent
and readily discernible with non-destructive/non-invasive, ophthalmic imaging
methods.
To date there are no treatments available for STGD disease. The only
recommendation for such patients is eye protection from bright light (e.g. by
using sun glasses) and to avoid exposure to substances that might cause eye
irritations, like tobacco smoke. These measures cannot prevent but may possibly
slow down disease progression. Existing approaches targeting lipofuscin are
restricted to limiting further accumulation of lipofuscin in the RPE cells to
avoid worsening of the disease progression. However, no treatment is currently
available to remove the already accumulated lipofuscin and to allow RPE cell
regeneration.
This study investigates the drug calles Soraprazan. This drug was initially
developed to stop acid production in the stomach to treat gastroesophageal
reflux disease (GERD). Soraprazan has been tested in several hundred patients
with GERD and caused no serious side effects. However, development was stopped
because there were many other products for use in GERD on the market. A study
in monkeys showed that soraprazan removed pigments from the retina. The main
pigment removed from the retina by soraprazan was lipofuscin. Since soraprazan
removes lipofuscin from the retina, it could be the first product that may help
in Stargardt Disease.
Study objective
Primary objective:
To evaluate the efficacy of soraprazan in reducing the amount of lipofuscin in
RPE cells of subjects with Stargardt disease by assessing the change in
quantitative auto-fluorescence (qAF8) from baseline to after treatment with
soraprazan compared to placebo for up to 12 months.
Secondary objective:
To assess the safety and efficacy of soraprazan based on safety parameters
and secondary efficacy parameters such as change in visual function and
structural changes after treatment with soraprazan compared to placebo for
up to 12 months.
Study design
The investigational drug soraprazan has demonstrated (in pre-clinical studies)
the ability to remove lipofuscin from RPE cells. The amount of lipofuscin in
RPE cells can be shown by its level of auto-fluorescence. A reduction of the
amount of lipofuscin in the RPE cells will result in reduced auto-fluorescence
signal. Quantitative Autofluorescence (qAF) is a technique to measure fundus
autofluorescence changes as a marker of lipofuscin levels in the retina.
This is a randomized proof of concept, double-masked, placebo-controlled, two
arm, multicenter trial to evaluate the efficacy and safety of soraprazan (20 mg
orally once a day) in subjects with Stargardt disease by measuring the
reduction of the amount of lipofuscin in the RPE cells subjets with qAF.
Retinal sensitivity will be measured by microperimetry.
90 subjects are planned to be randomized in 5 European sites in Germany, the
Netherlands, United Kingdom and Italy. Subjects with Stargardt disease will be
randomized to the trial treatment in a 2:1 ratio (soraprazan:placebo). Subjects
will be treated for up to 12 months.
Intervention
Soraprazan or placebo, 20mg orally once a day.
Study burden and risks
Previous GERD studies done by Altana Pharma with soraprazan have demonstrated a
good safety profile. Observed adverse events were mainly related to
gastrointestinal symptoms (such as flatulence, nausea, abnormal stools and
abdominal pain), dizziness, and headaches. Soraprazan 20 mg daily dose was well
tolerated by the majority of the subjects in these studies and was used for up
to 8 weeks.
In the present study, the same oral dose will be used as in the GERD studies.
All subjects will be closely monitored for safety parameters throughout the
study. In addition, all subjects will have the possibility to withdraw their
consent at any time, without giving any explanation. Subjects with already
known APA intolerance or reduced liver function will not be enrolled. Subject
safety will be observed and evaluated by a Data Safety and Monitoring Board
(DSMB) during the course of the study. Thus, the safety risk for subjects
participating in this clinical trial is considered to be low.
There is currently no cure or standard treatment available for STGD. Other
development projects for the treatment of STGD can only prevent further
accumulation of lipofuscin in the RPE. Thus there is no possibility for RPE
cell regeneration with these research approaches, and most STGD patients will
eventually lose visual function. Therefore, soraprazan aims to address this
medical need for lipofuscin removal in STGD.
Lederstr. 21
Tübingen 72127
DE
Lederstr. 21
Tübingen 72127
DE
Listed location countries
Age
Inclusion criteria
• Elevated qAF in at least one eye at screening (value >=300 Units).;• Male or female of any ethnicity and >= 18 years old.;• Onset of STGD disease before the age of 45 years;• Visual acuity of the study eye: BCVA 0.2-0.8 (decimal unit).;• Clinical diagnosis of typical autosomal recessive Stargardt*s macular dystrophy (STGD1).;• Genetic report indicating at least two ABCA4 mutations (one with confirmed pathogenesis by a certified lab, one reported previously).;• Study eye must have clear ocular media and adequate pupillary dilation, including no allergy to dilating eye drops and with sufficient fixation to permit good quality retinal imaging.;• Able and willing to comply with study requirements, restrictions and instructions and is likely to complete the 12-months study.;• Signed and dated informed consent form.;• Female subjects of childbearing potential and male subjects participating in the study who are sexually active must use acceptable contraception. Male and female subjects documented as being of non-child bearing potential (e.g. infertile, surgically sterile, postmenopausal) are exempt from the contraceptive requirements.
Exclusion criteria
• Intolerance to acid pump antagonists (APAs).;• Intake of prohibited medications/supplements (supplements containing vitamin A or beta-carotene, medications to treat any liver disease, or oral retinoid medications) within 28 days prior to screening and throughout the study.;• Intake of other drugs with a pH dependent absorption, e.g. ketoconazole.;• Breastfeeding, pregnant, or positive urine pregnancy test at screening or visit 2 (first intake of Investigational Medicinal Product (IMP)).;• At screening, clinically significant abnormal haematology or biochemistry findings.;• Acute or unstable severe disease or history of disease which in the opinion of the investigator would preclude participation in the study.;• Active or history of an additional ocular disorder in the primary study eye that, in the opinion of the investigator, may confound the study results. These include, but are not limited to, any reason that might interfere with the imaging techniques used in the study (such as optic media opacity or poor pupil dilatation), inflammatory eye disease, other retinal disorders besides STGD, confirmed glaucoma or baseline intraocular pressure of >=25mmHg, optic neuritis, high myopia (>8D spherical equivalent), amblyopia.;• Intraocular surgery or injections in the primary study eye within 180 days of the screening visit.;• Clinically significant abnormal electrocardiogram (ECG), or a corrected QT interval (QTc) of >=450 ms in males or >=470 ms in females.;• Participation in any other investigational clinical trials within 28 days of the screening visit.
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
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2018-001496-20-NL |
| CCMO | NL68179.091.18 |