None listed
Conditions
Brief summary
This is Part 1 of a 2-part study to evaluate the safety, tolerability and efficacy of TO-O-1007 IVT implantation in the eye of participants with Geographic Atrophy (GA) secondary to age-related macular degeneration (AMD). Part 1 of the study will test if it is safe to implant a low dose and then a higher dose of TO-O-1007 IVT in the eye of people with GA which is an advanced form of AMD and explore the effectiveness of the implant on GA progression. Age-related macular degeneration (AMD) is a disease of the macula, an area in the retina found at the back of the eye, needed for sharp, clear vision and activities such as reading and sewing. The advanced form of dry AMD is known as geographic atrophy (GA) (a region of the retina where the cells wither away and die). Sometimes, these regions of GA look like a map to the doctor who is examining the retina, hence the term “geographic atrophy.”
Interventions
This is part 1 of a 2 part study investigating safety and tolerability of a single dose TO-O-1007 intravitreal implantation in participants with GA secondary to AMD. The implant is designed for controlled drug release over a 24-week period.
Part 1 - Phase (Open-label, Single Ascending Dose):
6 subjects will be enrolled sequentially, with 3 subjects receiving a single intravitreal injection of TO-O-1007 at the low dose
(0.18 mg; 1 implant) and, following safety review, 3 subjects at the high do
This is part 1 of a 2 part study investigating safety and tolerability of a single dose TO-O-1007 intravitreal implantation in participants with GA secondary to AMD. The implant is designed for controlled drug release over a 24-week period. Part 1 - Phase (Open-label, Single Ascending Dose): 6 subjects will be enrolled sequentially, with 3 subjects receiving a single intravitreal injection of TO-O-1007 at the low dose (0.18 mg; 1 implant) and, following safety review, 3 subjects at the high dose (0.36mg; 2 implants) on each subject’s Day 1. Each cohort will then continue study participation for 24 weeks followed by a 4-week follow-up period.
Sponsors
TheratOcular Biotech Australia Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The study eye must meet all inclusion criteria. If both eyes are eligible, the eye with the worse visual acuity at the screening visit will be designated as the study eye. If both eyes have equal visual acuity, the right eye will be selected. 1. Subject is male or female and aged greater than or equal to 50 years at the time of informed consent. 2. Subject is willing and able to provide written informed consent and comply with all study-related procedures and assessments. 3. Women of non-childbearing potential (WONCBP), or women of childbearing potential (WOCBP) with: o A negative urine pregnancy test at screening. o Agreement to use protocol-defined contraception throughout the study and for at least 60 days after the last dose. o Agreement to refrain from breastfeeding during the study and for at least 60 days after the last dose. 4. Sexually active male subjects must agree to use protocol-defined contraception and refrain from donating sperm for the duration of the study. 5. Clinical diagnosis of non-foveal geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD), confirmed by both the investigator and the central reading center. 6. Total GA lesion area must be greater than or equal to 2.5 mm² and less than or equal to 17.5 mm² (equivalent to 1–7 disc areas), as determined by FAF imaging and confirmed by the central reading center. 7. For multifocal GA, at least one focal lesion must be greater than or equal to 1.25 mm² (0.5 disc area), as determined by fundus autofluorescence (FAF) imaging and confirmed by the central reading center, and the total aggregate area must still meet criterion 6. 8. The entire GA lesion must be fully visible in a macula-centered image, not contiguous with any area of peripapillary atrophy, as confirmed by the central reading center. 9. Presence of any hyperautofluorescence pattern in the junctional zone of the GA lesion, as determined by FAF imaging and confirmed by the central reading center. 10. BCVA in the study eye of greater than or equal to 24 ETDRS letters (approximately 20/320 Snellen equivalent), assessed using an ETDRS chart at a standard testing distance (typically 4 meters) under standard photopic conditions. 11. Adequate ocular media clarity, sufficient pupillary dilation, and stable fixation to allow for high-quality retinal imaging, as determined by the investigator. 12. Intraocular pressure (IOP) of less than or equal to 21 mmHg in the study eye at screening. 13. Meets all the following microperimetry criteria in the study eye: (if assessed) The following criteria apply only to subjects undergoing mesopic microperimetry assessment at sites where this assessment is performed. • Able to detect the fixation target. • Completion of the 10-2, 68-point test within 30 minutes. • Fixation losses less than or equal to 20%. • In the investigator’s opinion, the subject is willing and able to complete microperimetry assessments.
Exclusion criteria
Subjects meeting any of the following criteria at screening will be excluded from the study. 1. Prior participation in another interventional clinical study for intravitreal therapies in either eye (including subjects receiving sham) within 6 months prior to the Screening Visit. 2. Prior participation in another interventional clinical study for geographic atrophy in either eye including investigational oral medication and placebo within 6 months prior to the Screening Visit. 3. Prior or planned treatment with any ocular or systemic gene therapy (e.g., AAV-mediated therapies or other genetic modification therapies) at any time prior to Screening or during study participation. 4. Participation in any systemic experimental treatment or any other systemic investigational new drug within 6 weeks or 5 half-lives of the active ingredient (whichever is longer) prior to the start of study treatment. 5. Women who are pregnant or nursing. 6. Known serious allergies to the fluorescein dye used in angiography or to the components of the TO-O-1007 formulation. 7. Absence of hyperautofluorescence in the junctional zone of the GA lesion (i.e., hyperautofluorescence pattern = none). 8. Spherical equivalent of the refractive error demonstrating > 8 diopters of myopia or an axial length > 27 mm. 9. GA secondary to a condition other than AMD such as Stargardt disease, cone rod dystrophy, or toxic maculopathies like plaquenil maculopathy in either eye. 10. Any prior treatment for AMD or any prior IVT treatment for any indication in either eye, except oral supplements of vitamins or minerals within 6 months prior to the Screening Visit. 11. Active CNV in the study eye, as determined by the investigator. The presence of CNV in the fellow eye is permitted. If CNV develops in the study eye during the course of the study, the subject will be withdrawn from the study. 12. Presence of other causes of CNV, including pathologic myopia (spherical equivalent of -8 diopters or more, or axial length of 25 mm or more), ocular histoplasmosis syndrome, angioid streaks, choroidal rupture, and multifocal choroiditis. 13. Any ocular condition in the study eye that would progress during the course of the study that could affect central vision or otherwise be a confounding factor. 14. Any sign of diabetic retinopathy in either eye, as determined by the investigator. 15. Presence of intraocular inflammation (greater than or equal to trace cell or flare), macular hole, pathologic myopia, epiretinal membrane, evidence of significant vitreo-macular traction, vitreous hemorrhage or aphakia, as determined by an investigator. (pseudophakia with or without an intact capsule is not an exclusion criteria). 16. Any ocular or periocular infection (including blepharitis), or ocular surface inflammation in the past 12 weeks. 17. History or evidence of severe cardiac disease (e.g., New York Heart Association Functional Class III or IV), history or clinical evidence of unstable angina, acute coronary syndrome, myocardial infarction, or revascularization within last 6 months, ventricular tachyarrhythmias requiring ongoing treatment. 18. History or evidence of clinically significant peripheral vascular disease, such as intermittent claudication or prior amputation. 19. Clinically significant impaired renal (serum creatinine > 2.5 mg/dL or status post-renal transplant or receiving dialysis) or hepatic function. Subjects with results outside these ranges may be enrolled after consultation with TheratOcular. 20. History of stroke with residual neurological or visual deficits that may interfere with study assessments, or that may increase medical risk in the opinion of the investigator. Subjects with a prior minor stroke or TIA without residual deficits may be eligible. 21. Any major surgical procedure within 1 month of study entry. 22. Presence or history of idiopathic or autoimmune-associated uveitis in either eye. 23. History of systemic treatment with any anti-complement agent within 9 months prior to the Screening Visit, or an anticipated need for any systemic anti complement agent during the study. 24. Concomitant treatment with any ocular or non-ocular medication that is known to be toxic to the lens, retina, or optic nerve. 25. Intraocular surgery (including lens replacement surgery) within 3 months prior to randomization. 26. History of laser therapy in the macular region. 27. History of any of the following procedures: Posterior vitrectomy, filtering surgery (e.g.,trabeculectomy), glaucoma drainage device, corneal transplant, or retinal detachment. 28. Aphakia or absence of the posterior capsule. Note: YAG laser posterior capsulotomy for posterior capsule opacification done at least 60 days prior to screening is not exclusionary. 29. Unable to perform microperimetry reliably in the opinion of the investigator. 30. Use of prohibited ocular or systemic medications as listed below, due to potential confounding effects on inflammation, retinal structure, or GA progression: • Investigational ocular products: Any investigational periocular, or topical ocular drug within 6 months prior to Screening. • Systemic immunosuppressive or biologic agents: Chronic systemic immunosuppressants, systemic biologics, or immunosuppressive-dose corticosteroids within 3 months prior to Day 1. • High-frequency topical ocular anti-inflammatory therapy: Intensive topical corticosteroids or NSAIDs not discontinued = 14 days prior to Day 1. • High-dose vitamin A or experimental nutraceutical therapy: High-dose vitamin A or non-standard nutraceuticals for AMD/ocular health within 30 days prior to Day 1.
Outcome results
None listed