First in Human Study of BETA-TT8 in wetAge-related Macular Degeneration (wetAMD)
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age50+
SponsorFilamon LTD
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
BETA-TT8 ophthalmic gel 3.8% w/v
DrugA selective small-molecule inhibitor of the MEK/ERK (MAPK) signalling pathway, topical ophthalmic gel.
Treatment groups
24 Participants
are divided into 3 treatment groupsGroup A: BETA-TT8 Ophthalmic topical gel - Group oneActive comparator 1 intervention
Group B: BETA-TT8 Ophthalmic topical gel - Group twoActive comparator 1 intervention
Group C: BETA-TT8 Ophthalmic topical gel - Group threeActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
To evaluate the safety of topical BETA-TT8 based on TEAEs.
• 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.
Time frame
12 weeks2
To evaluate the safety of topical BETA-TT8 based on DLTs.
• 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
Time frame
12 weeks3
To evaluate the safety of topical BETA-TT8 based on clinically significant ocular findings.
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.
Time frame
12 weeks4
To evaluate the safety of topical BETA-TT8 based on intraocular pressure changes.
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.
Time frame
12 weeksSecondary outcomes
1
To further characterise ocular safety following repeated topical administration based on preliminary biological activity data.
Based on Optical Coherence Tomography (OCT)-derived anatomical measures, including: • Mean change from baseline in Central Subfield Thickness (CST) at each scheduled visit.
Time frame
12 weeks2
Exploratory-efficacy signals during BETA-TT8 treatment phase.
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.
Time frame
12 weeks3
Exploratory-efficacy signals during BETA-TT8 treatment phase.
Exploratory efficacy signals, if identified, will inform endpoint selection and sample size determination for future adequately powered studies. • Number of Aflibercept rescue injections during the 12-week treatment phase, referenced descriptively against site-derived historical anti-VEGF injection-burden data.
Time frame
12 weeks4
Exploratory-efficacy signals during BETA-TT8 treatment phase.
Exploratory efficacy signals, if identified, will inform endpoint selection and sample size determination for future adequately powered studies. • Within-patient change in anti-VEGF rescue interval relative to each patient's own documented pre-study injection interval.
Time frame
12 weeksOther outcomes
1
To assess systemic exposure effects of BETA-TT8 over the Extension Phase
Systemic exposure effects will be captured through fellow-eye (i.e. non-treated eye) safety assessments measuring mean change in BVCA (ETDRS letters) from baseline to each scheduled visit.
Time frame
12 months2
To assesses potential efficacy of BETA-TT8 over the Extension Phase
At each scheduled visit during the Extension Phase, BCVA (ETDRS letters) assessment will be performed measuring mean change from baseline to each scheduled visit as previously described.
Time frame
12 months3
To characterise aflibercept injection burden over the 12-month Extension Phase
This will be done by recording the cumulative number of rescues (aflibercept injection) required over the Extension Phase, compared to site-derived historical anti-VEGF standards.
Time frame
12 months4
To assesses potential efficacy of BETA-TT8 over the Extension Phase
At each scheduled visit during the Extension Phase, CST assessments will be performed as previously described.
Time frame
12 monthsSponsors and contacts
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Source ClinicalTrials.gov
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