Neovascular (Wet) Age-Related Macular Degeneration
Conditions
Keywords
BETA-TT8, wetAMD, Ophthalmic gel, neovascular AMD, ophthalmology
Brief summary
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.
Detailed description
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.
Interventions
DRUGBETA-TT8 ophthalmic gel 3.8% w/v
A selective small-molecule inhibitor of the MEK/ERK (MAPK) signalling pathway, topical ophthalmic gel.
Sponsors
Filamon LTD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single dose, with dose frequency the only variable, patients randomised to one of three arms; One drop once daily; one drop twice daily; or one drop three times daily into study eye/s
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the tolerability of topical BETA-TT8 based on reasons for discontinuations. | 12 weeks | Incidence of treatment discontinuations due to adverse events. |
| To evaluate the safety of topical BETA-TT8 based on TEAEs. | 12 weeks | • Incidence of treatment-emergent adverse events (TEAEs) and ocular TEAEs through Week 12, coded using MedDRA and graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0. |
| To evaluate the safety of topical BETA-TT8 based on DLTs. | 12 weeks | • Incidence of dose-limiting toxicities (DLTs) within pre-defined evaluation windows. A DLT is defined as any of the following events considered at least possibly related to BETA-TT8. Systemic DLTs; * Any Grade 3 or higher adverse event per CTCAE v5.0. * Any drug-related Grade 2 adverse event sustained for more than 7 days. * ALT or AST greater than 3× ULN with total bilirubin greater than 1.5× ULN. * Grade 3 or higher haematological toxicity. * QTcF greater than 500 ms, or an increase in QTcF greater than 60 ms from baseline, confirmed on repeat ECG. Ocular DLTs; * Clinically significant corneal toxicity (Grade 2 or higher on NEI/Oxford scale sustained more than 7 days, or any Grade 3 finding). * Anterior chamber inflammation above the pre-specified grading threshold. * Clinically significant IOP increase, defined as an increase greater than 10 mmHg from baseline AND an absolute IOP greater than 30 mmHg, confirmed on repeat measurement. * Clinically meaningful decrease in BCVA |
| To evaluate the safety of topical BETA-TT8 based on clinically significant ocular findings. | 12 weeks | Incidence of clinically significant ocular findings on slit-lamp and fundoscopic examination (cornea, conjunctiva, anterior chamber, lens, vitreous, retina). Corneal epithelial findings (including punctate keratopathy) are specifically monitored as a precaution for topical ocular small molecules. |
| To evaluate the safety of topical BETA-TT8 based on intraocular pressure changes. | 12 weeks | Incidence of clinically significant intraocular pressure (IOP) changes, defined as an increase greater than 10 mmHg from baseline or absolute IOP greater than 30 mmHg. |
| To evaluate the safety of topical BETA-TT8 based on corneal staining abnormalities. | 12 weeks | Incidence of corneal epithelial defects/staining abnormalities graded per National Eye Institute (NEI) or Oxford scale. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To further characterise ocular safety following repeated topical administration based on preliminary biological activity data. | 12 weeks | Based on Optical Coherence Tomography (OCT)-derived anatomical measures, including: • Mean change from baseline in Central Subfield Thickness (CST) at each scheduled visit. |
| Exploratory-efficacy signals during BETA-TT8 treatment phase. | 12 weeks | Exploratory efficacy signals, if identified, will inform endpoint selection and sample size determination for future adequately powered studies. • Time to first Aflibercept rescue (Kaplan-Meier) , referenced descriptively against site-derived historical anti-VEGF injection-burden data. |
Countries
Australia
Contacts
CONTACTHemal Mehta, MBBS MD, FRCOphth FRANZCO
CONTACTSarrvesa Singh
PRINCIPAL_INVESTIGATORHemal Mehta, MBBS MD, FRCOphth FRANZCO
Central Coast Eye Specialists
Outcome results
None listed