A Phase Ib/IIa, First-in-Human, Open-Label Study to Evaluate the Safety, Tolerability, and Exploratory Activity of BETA-TT8 Ophthalmic Gel 3.8% in Patients With Neovascular (Wet) Age-related Macular Degeneration (wetAMD)
This is a first-in-human clinical trial evaluating the safety and tolerability of BETA-TT8 Ophthalmic Gel in people with wet age-related macular degeneration (AMD). Approximately 24 participants with stable wet AMD who have previously received at least three anti- Vascular Endothelial Growth Factor (anti -VEGF) injections will use the eye gel for up to 12 weeks at one of three dosing schedules (once, twice, or three times daily). Standard anti-VEGF treatment (aflibercept) will remain available if needed during the study. Participants who complete the initial 12-week treatment period may be invited to continue in an extension phase for up to 12 months to collect additional safety and treatment information.
This is a Phase Ib/IIa, first-in-human, open-label, multi-centre study of BETA-TT8 Ophthalmic Gel 3.8% in patients with neovascular (wet) age-related macular degeneration. BETA-TT8 is administered topically to the study eye. The study enrols twenty-four (24) patients recently diagnosed with wetAMD and stable on standard-of-care anti-VEGF at entry (stable being defined as absence of intraretinal fluid, less than 200microns of subretinal fluid, no new macula haemorrhage and stable visual acuity-less than 5 Early Treatment Diabetic Retinopathy Study (ETDRS) letter difference- over the last two visits), in three parallel groups of eight (8) per group. BETA-TT8 is added to each patient's established anti-VEGF backbone at a single fixed dose, identical across all three groups. Patients first receive a minimum of three loading intravitreal aflibercept 2 mg injections per the approved label. BETA-TT8 is then introduced approximately one week after the third or more injections. Aflibercept remains available as rescue throughout; BETA-TT8 dosing continues during and after rescue. All patients are randomised to one of three groups for the 12-week period (Group 1: Once-daily (OD); Group 2: Twice-daily (BD); Group 3: Three-times-daily (TDS)). Dose per administration is identical throughout and across groups; dosing frequency is the only variable. This is a safety and tolerability evaluation; dosing-frequency-finding is a pre-specified exploratory aim. Participants meeting the pre-specified Extension Gate criteria at Week 12 may enter a 12-month open-label extension.
Inclusion Criteria: * Age 50 years or older. * Subfoveal or juxtafoveal choroidal neovascularisation (CNV) secondary to AMD in the study eye(s). * Stable disease having received three (3) or more previous intravitreal aflibercept 2mg as standard-of-care. * Total CNV lesion area no greater than 12-disc areas. * BCVA in the study eye between 24 and 78 ETDRS letters inclusive. * Suitable for intravitreal aflibercept rescue per its approved label. * Able to self-administer eye drops or has a trained caregiver able to administer drops at home. * Willing and able to comply with the protocol-defined visit schedule. * Signed informed consent.
Exclusion Criteria: * Ocular Exclusion Criteria * Contraindication to intravitreal aflibercept per its approved label, including active ocular or peri-ocular infection or active intraocular inflammation. * Dense fibrosis or scarring within the study eye(s) lesion limiting OCT interpretation. * Severe atrophy involving the fovea. * Subretinal haemorrhage involving or obscuring the fovea. * Subretinal fibrosis involving more than 50% of the lesion area. * Pigment epithelial detachment involving more than 50% of the CNV lesion. * Confounding retinal disease, including diabetic retinopathy, retinal vein occlusion, or myopic degeneration. * Significant corneal disease that would complicate topical safety interpretation. * Prior subfoveal laser photocoagulation, photodynamic therapy, or ocular radiation in the study eye. * Uncontrolled glaucoma or IOP greater than 25 mmHg at screening. * Systemic Exclusion Criteria * Clinically meaningful ECG abnormality or QTcF concern at baseline (QTcF greater than 460 ms in men or greater than 480 ms in women). * Current use of QT-prolonging medications per a pre-specified list * Current use of medications with known MEK or MAPK pathway activity. * Clinically significant hepatic, renal, cardiovascular, or haematological disease. * Known hypersensitivity to any component of the BETA-TT8 formulation or to aflibercept. * Active malignancy or history of malignancy requiring treatment within the prior 5 years. Cancers considered to be cured (eg. prostatectomy or radiation for prostate cancer, adjuvant treatment for breast cancer) or treated non-metastatic skin or melanoma are excepted. * Pregnancy, breastfeeding, or inadequate contraception during the study and for 30 days after last dose of BETA-TT8. * Other Exclusion Criteria * Inability or unwillingness to comply with study procedures or dosing requirements. * Cognitive impairment or insufficient home support that may compromise proper administration of study treatment. * Participation in another investigational study within 30 days of screening.
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