Macular dystrophies are a group of inherited eye conditions that affect the macula. The macula is in the center of the retina, the light sensitive part at the back of the eye. In people with macular dystrophies, some of the cells in the macula gradually stop working and may die over time. This leads to loss of central vision, which can make it harder to read, recognize faces or see fine details. What's seen out of the corner of the eye (peripheral vision) is mostly unaffected. Stargardt disease (STGD) is a type of macular dystrophy which is caused by 1 faulty gene (ABCA4). Vision loss most typically begins in childhood or teenage years but may also develop in adulthood. As well as STGD, there are other macular dystrophies that look very similar to STGD and are called STGD-like macular dystrophies. These are caused by many other different genes. Together, STGD and STGD-like conditions can be called STGD-type macular dystrophies.
This is an early development study of ASP2020 in adults, teenagers, and children with STGD-type macular dystrophies. ASP2020 are human stem cells which have been changed into cells found in the macula. In this study ASP2020 will be given to people for the first time. The main aim of the study is to check the safety of ASP2020 and how well people tolerate it. Other aims are to learn if people have an immune reaction to ASP2020, and if there are signs that the stem cells replace damaged cells in the retina, and vision improves for people with STGD-type macular dystrophies.
ASP2020 will be given as a single injection into the eye, under the retina. This requires a surgical procedure where the person is put to sleep by a general anesthetic. At the end of surgery, a steroid will be injected into the eye to reduce any swelling.
The study has 2 parts. In Part 1, different small groups will receive a lower to higher dose of ASP2020. This is done to find a suitable dose to use in Part 2. The adults will receive the lower dose and higher dose before the teenagers. There will be a 6-month gap between the last adult receiving the lower dose of ASP2020 and the first teenager receiving the same lower dose. This will also happen for the last adult receiving the higher dose of ASP2020 and the first teenager receiving the higher dose of ASP2020. Any medical problems will be recorded for each dose in each group. Children will not receive ASP2020 in Part 1.
In Part 2, different groups of adults, teenagers and children will receive the most suitable dose of ASP2020 worked out from Part 1.
People will be in the study for about 1 year and they will visit the clinic several times. In both parts of the study, safety checks will be done at each visit, and the study doctors will continue to check for any medical problems throughout the study. Various eye tests and eye imaging will be done throughout the study. Blood tests will also be done at some of the visits during the study.
STGD: presence of biallelic (pathogenic or likely pathogenic) ABCA4 variants, or one definite disease-causing ABCA4 variant together with a typical phenotype consistent with STGD.
STGD-like macular dystrophy: presence of one or more pathogenic variants in a gene known to cause macular dystrophy, as appropriate for its expected inheritance mode.
Sufficiently clear ocular media and adequate pupillary dilation to allow for all imaging procedures.
Intraocular pressure (IOP) of ≤ 21 mmHg
Participant has a known history of significant systemic disease that could impact ocular health or confound study assessments, based on medical history or prior clinical documentation.
Participant has an autoimmune condition that requires treatment with immunomodulatory therapy and/or biologics that cause immunosuppression.
Participant has known diagnosis of diabetes mellitus with a documented glycated hemoglobin (HbA1c) value ≥ 7% 3 months prior to screening and based on available medical records.
Participant has a history or evidence of severe cardiac disease, cardiovascular or cerebrovascular disease, including a history of stroke within 12 months prior to screening.
Sequential
ASP2020
DrugSubretinal Injection
6
Treatment groupsSee each treatment group below.
Number of participants with treatment-emergent adverse events (TEAEs)
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs are defined as an AE observed after administration of ASP2020 or pre-existing AE that worsen in severity or frequency following administration of ASP2020.
Number of participants with serious adverse events (SAEs)
An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or other medically important events.
Number of participants with adverse events of special interest (AESIs)
AESIs include, but are not limited to, the following: * Ectopic, excessive, or aberrant cell growth of ASP2020, including proliferative changes * Immune-mediated reactions, including unexpected or clinically significant inflammatory responses * Any new diagnosis of malignancy * Any clinically significant AEs possibly or definitely related to ASP2020 * Clinically significant AEs related to the surgical administration procedure
Number of participants with greater than or equal to 15 letter loss in best corrected visual acuity (BCVA) from baseline
BCVA will be measured from the Early Treatment of Diabetic Retinopathy Study (ETDRS) letters chart.
Change from baseline in BCVA
BCVA will be measured from the ETDRS letters chart.
Change from baseline in low luminance visual acuity (LLVA)
LLVA will be measured from the ETDRS letters chart.
Change from baseline in Minnesota Reading Acuity Chart (MNREAD) parameters
MNREAD evaluates near reading acuity, reading speed and critical print size.
Change from baseline in mesopic macular sensitivity
Mean sensitivity, point-wise sensitivity (PWS), scotomatous/non-seen point count) will be measured by mesopic microperimetry.
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