Age-Related Macular Degeneration
Conditions
Keywords
Geographic Atrophy, Age-related Macular Degeneration, ASP7317
Brief summary
Age-related macular degeneration (AMD) is an eye disease which causes people to lose their sharp central vision over time. Aging damages the macula, which is in the middle of the retina - the light-sensitive part at the back of the eye. There are 2 types of AMD - wet AMD and dry AMD. The advanced stage of dry AMD causes vision loss. This is known as geographic atrophy. AMD makes everyday tasks like reading or driving difficult. ASP7317 is a potential new treatment for people with AMD. ASP7317 are human stem cells which have changed into cells found in the retina. ASP7317 is injected under the macula. It is hoped that ASP7317 will replace some of the damaged cells in the macula and improve vision for people with dry AMD. Before ASP7317 is available as a treatment, the researchers need to check its safety and how well it is tolerated. They will also check for signs of improved vision. People taking part in this study will be older people who have geographic atrophy caused by dry AMD. This is an open-label study. This means that people in this study and clinic staff will know that people will receive ASP7317. There will be 3 doses of ASP7317. These are low, medium and high numbers of cells. ASP7317 will be injected under the macula after the person is given either a local or a general anesthetic. To prevent the body from rejecting the cells, people will take tablets of tacrolimus a few days before receiving ASP7317 for up to a few weeks afterwards. Other medicines will be taken during this time to stop infections. There will be 2 groups in the study. Group 1 will be people with severe vision loss and Group 2 will be people with moderate vision loss. There will be different small groups of people within Group 1 and Group 2, with each small group receiving 1 of the 3 doses of ASP7317. Different small groups of people within Group 1 and Group 2 will receive lower to higher doses of ASP7317. Each small group will only receive 1 dose. Group 1 will start treatment first. At each dose, a medical expert panel will check the results of the first person in the group to decide if the rest of the group will receive the same dose. Then, the panel will decide if more people may receive the same dose or if the next group may receive the next highest dose. The panel will use the results from the lower dose of Group 1 to decide when Group 2 starts treatment (also at the lower dose). The panel will also use the results of the middle and higher doses in Group 1 to decide when and how many people in Group 2 can receive these doses. During the study, people will visit the clinic several times for up to 12 months (1 year). During all visits, the study doctors will check for any medical problems after receiving ASP7317. Vital signs will be checked a few days before treatment with ASP7317 and up to about a month afterwards. Vital signs include blood pressure, pulse, and temperature. At some visits, the study doctors will also take blood samples for blood tests. At most visits, people will have eye tests and have different images, scans, and measurements taken. This could be for the affected eye or both eyes, depending on the test. People can visit the clinic extra times, if needed.
Detailed description
The study consists of the following periods: Screening (up to 60 days) and the Study Period (52 weeks post treatment).
Interventions
DRUGASP7317
subretinal injection
DRUGtacrolimus
oral
DRUGtrimethoprim-sulfamethoxazole
oral
DRUGAcyclovir
oral
DRUGNystatin
oral
Sponsors
Astellas Institute for Regenerative Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General Inclusion Criteria * Participant must be willing to take tacrolimus and willing to discontinue any medications that have a known strong interaction with tacrolimus. * Participant is able and willing to undertake all scheduled visits and assessments up to the week 52 visit. * Participant who is taking an antidepressant must be on a stable and effective dosage and must be willing to take it reliably for as long as it is required. * Participant must be willing and medically suitable to undergo monitored anesthesia care during the vitrectomy and subretinal injection. * Participant agrees to conform to local and institutional policies regarding active COVID-19 infections. * Participant agrees not to participate in another interventional study until the 52-week visit has been completed. * Female participant is not pregnant or at least 1 of the following conditions apply: * Not a woman of childbearing potential (WOCBP) * WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 52 weeks after investigational product (IP) administration. * Female participant must agree not to breastfeed starting at screening and throughout the study period and for 52 weeks after IP administration. * Female participant must not donate ova starting at first dose of IP and throughout the study period and for 52 weeks after IP administration. * Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 52 weeks after IP administration. * Male participant must not donate sperm during the treatment period and for 52 weeks after IP administration. * Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 52 weeks after IP administration. Ocular Inclusion Criteria: Study Eye (Both Groups 1 and 2) * Participant has bilateral AMD and geographic atrophy (GA) secondary to Age-Related Macular Degeneration (AMD) in the study eye. GA is defined as sharply demarcated areas of loss of the retinal pigment epithelial/epithelium (RPE). While having bilateral GA remains the preferred enrollment criterion, it is not a requirement and GA only in the study eye is admissible, as long as both eyes exhibit AMD. * Participant has no known history of choroidal neovascularization (CNV) (wet AMD) in either eye prior to enrollment in the trial and no evidence of prior or active CNV with optical coherence tomographyangiography (OCT-A) or indocyanine green angiography (ICG-A), as assessed by the reading center. * Participant has absence of exudation as assessed by fluorescein angiography (FA) and spectral domain-optical coherence tomography (SD-OCT). * Participant has sufficiently clear ocular media, adequate pupillary dilation, and fixation to permit quality fundus imaging. * Participant is pseudophakic. Ocular Inclusion Criteria: Study Eye (Group 1 only) * For cohort 1, the participant has a BCVA between light perception and \</=23 Early Treatment Diabetic Retinopathy study (ETDRS) letters at the screening visit. For cohorts 2 and 3, the participant has a BCVA score between 15 (\>/= 20/500) and 37 (\</=20/200) ETDRS letters at the screening visit. * Participant has the total GA area \</=30.5 mm\^2 (\</=12 disc areas \[DA\]). Ocular Inclusion Criteria: Study Eye (Group 2 only) * Participant has BCVA score between 38 (\>20/200) and 65 (\</=20/50) ETDRS letters during the screening visit. * Participant has the total GA area of \>/= 2.54 mm\^2 and \</= 20.4 mm\^2 (\>/=1 and \</=8 DA, respectively) and must reside completely within the fundus autofluorescence (FAF) imaging field (Field 2 to 30 degree image centered on the fovea). * Participant has a difference in mean mesopic sensitivity \</=2 dB between 2 tests at screening. If not \</=2 dB, a third test may be conducted and mean values between the second and third assessments must be \</=2 dB.
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety as assessed by incidence, frequency and severity of treatment emergent adverse events (TEAES) | Up to 52 Weeks | Adverse events (AEs) will be coded using Medical Dictionary for Regulatory Activities (MedDRA). An Adverse Event is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of ASP7317, the adjunct study medications and the study procedures, whether or not considered related to ASP7317, the adjunct study medications and the study procedures. A Treatment Emergent Adverse Event (TEAE) is defined as an AE beginning or worsening in severity after starting administration of the adjunct study medication. |
| Safety as assessed by incidence, frequency and severity of Serious Adverse Events (SAEs) | Up to 52 Weeks | 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; results in congenital anomaly or birth defect or other medically important events. |
| Safety assessed by Adverse Events (AEs) of special interest | Up to 52 Weeks | AEs of special interest include: ectopic or proliferative cell growth (retinal pigment epithelial/epithelium (RPE) or non-RPE) with adverse clinical consequence; any new diagnosis of an immune-mediated disorder; any new cancer, irrespective of prior history; unexpected, clinically significant AEs possibly related to the cell transplant procedure; immunosuppressive therapy (IMT) or ASP7317 (e.g., graft failure or rejection). |
| Number of participants with cellular graft failure or rejection | Up to 52 Weeks | Evidence of cellular graft failure or rejection will be assessed by best corrected visual acuity (BCVA), slit lamp examination, dilated indirect ophthalmoscopy, fundus photographs, spectral domain-optical coherence tomography (SD-OCT) and fluorescein angiography (FA), when performed. |
| Incidence of cellular graft failure or rejection | Up to 52 Weeks | Evidence of cellular graft failure or rejection will be assessed by best corrected visual acuity (BCVA), slit lamp examination, dilated indirect ophthalmoscopy, fundus photographs, spectral domain-optical coherence tomography (SD-OCT) and fluorescein angiography (FA), when performed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean change from baseline in point wise sensitivity (PWS) in treatment zone | Baseline, Weeks 4, 12, 26 and 52/End of Study (EOS) | Point-wise sensitivity will be measured using sensitivity results obtained in the treatment zone as assessed by imaging criteria. Treatment zone in the study eye is defined as the area that corresponds to the subretinal bleb area identified by the day 0 fundus photograph. |
| Mean change from baseline in PWS in extended treatment zone | Baseline, Weeks 4, 12, 26 and 52/End of Study (EOS) | Point-wise sensitivity will be measured using sensitivity results obtained in the extended treatment zone as assessed by imaging criteria. Treatment zone in the study eye is defined as the area that corresponds to the subretinal bleb area identified by the day 0 fundus photograph. Equivalent treatment zone in the fellow eye is defined as the quadrant that meets the criteria for the location for ASP7317 injection, as determined by the investigator. |
| Mean change from baseline in PWS in remote zone | Baseline, Weeks 4, 12, 26 and 52/End of Study (EOS) | Point-wise sensitivity will be measured using sensitivity results obtained in the remote zone as assessed by imaging criteria. Remote zone is defined as retina outside and opposite to the treatment zone. |
| Mean change from baseline in area of Geographic Atrophy (GA) (mm^2) in study eye and fellow eye | Baseline, Weeks 26 and 52/End of Study (EOS) | GA will be measured by blue-light fundus autofluorescence (FAF) (definitely decreased autofluorescence (DDAF)) and spectral domain-optical coherence tomography (SD-OCT) (area of ellipsoid zone (EZ) defect, area of outer nuclear layer (ONL) defect). |
| Mean change from baseline in number of scotomatous points | Baseline, Weeks 4, 12, 26 and 52/End of Study (EOS) | Scotomatous points (loci) will be measured using imaging measures. The number of scotomatous points is the total number of points that were not seen (\<0 dB loci). |
| Mean change from baseline in fixation stability (95% bivariate contour ellipse area (BCEA)) | Baseline, Weeks 4, 12, 26 and 52/End of Study (EOS) | Fixation Stability will be measured using imaging measures obtained during the microperimetry testing session, categorized as stable, relatively unstable and unstable. Categorization of stability based on % of fixation points within a specified diameter circle centered in the gravitational center of all fixation points. Stable-More than 75% of fixation points located within 2 degree diameter circle. Relatively Unstable-Less than 75% of fixation points located within 2 degrees diameter circle, but more than 75% of fixation points located within 4 degree diameter circle. Unstable-Less than 75% of fixation points located within 4 degree diameter circle. |
| Mean change from baseline in distance of preferred retinal locus (PRL) from Fovea | Baseline, Weeks 4, 12, 26 and 52/End of Study (EOS) | Distance of PRL from Fovea will be measured using imaging measures obtained during the microperimetry testing session. Participant with central vision loss obtain visual information with a preferred eccentric retinal area for visual tasks because of their central scotoma. This area is called the preferred retinal locus. |
| Mean change from baseline in PWS in extended remote zone | Baseline, Weeks 4, 12, 26 and 52/End of Study (EOS) | Point-wise sensitivity will be measured using sensitivity results obtained in the extended remote zone as assessed by imaging criteria. Remote zone is defined as retina outside and opposite to the treatment zone. |
| Mean percent change from baseline in area of Geographic Atrophy (GA) (mm^2) in study eye and fellow eye | Baseline, Weeks 26 and 52/End of Study (EOS) | GA will be measured by blue-light fundus autofluorescence (FAF) (definitely decreased autofluorescence (DDAF)) and spectral domain-optical coherence tomography (SD-OCT) (area of ellipsoid zone (EZ) defect, area of outer nuclear layer (ONL) defect). |
| Mean change from baseline in the square root transformation of Geographic Atrophy (GA) area in study eye and fellow eye | Baseline, Weeks 26 and 52/End of Study (EOS) | GA will be measured by blue-light fundus autofluorescence (FAF) (definitely decreased autofluorescence (DDAF)) and spectral domain-optical coherence tomography (SD-OCT) (area of ellipsoid zone (EZ) defect, area of outer nuclear layer (ONL) defect). |
| Mean change from baseline in best corrected visual acuity (BCVA) score in study eye and fellow eye | Baseline, Weeks 1, 4, 6, 8, 12, 16, 26 and 52/End of Study (EOS) | BCVA will be measured by an assessor certified to use the Early Treatment of Diabetic Retinopathy Study (ETDRS) method. The BCVA score (in letter units) will be reported. |
| Mean change from baseline in mean sensitivity | Baseline, Weeks 4, 12, 26 and 52/End of Study (EOS) | Mean sensitivity is the mean over all point-wise sensitivity zones. Point-wise sensitivity will be estimated using imaging measures obtained across all zones, treatment area and remote zone. |
Countries
United States
Contacts
Primary ContactAstellas Institute for Regenerative Medicine
Outcome results
None listed