Skip to main content
OpenTrials
Not yet recruiting

NCT Number: NCT07766473

First in Human Study of BETA-TT8 in wetAge-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.

Not yet recruiting

Trial opening soon.

Get Notified

Key information

Conditions

Neovascular (Wet) Age-related Macular Degeneration Eye Diseases Macular Degeneration Retinal Degeneration Retinal Diseases

Age range

50 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Central Coast Eye Specialist, Gosford, New South Wales, Australia

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

BETA-TT8 ophthalmic gel 3.8% w/v

Drug

A selective small-molecule inhibitor of the MEK/ERK (MAPK) signalling pathway, topical ophthalmic gel.

Primary outcomes

  1. To evaluate the safety of topical BETA-TT8 based on TEAEs.

    Time frame: 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.

  2. To evaluate the safety of topical BETA-TT8 based on DLTs.

    Time frame: 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

  3. To evaluate the safety of topical BETA-TT8 based on clinically significant ocular findings.

    Time frame: 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.

  4. To evaluate the safety of topical BETA-TT8 based on intraocular pressure changes.

    Time frame: 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.

  5. To evaluate the safety of topical BETA-TT8 based on corneal staining abnormalities.

    Time frame: 12 weeks

    Incidence of corneal epithelial defects/staining abnormalities graded per National Eye Institute (NEI) or Oxford scale.

  6. To evaluate the tolerability of topical BETA-TT8 based on reasons for discontinuations.

    Time frame: 12 weeks

    Incidence of treatment discontinuations due to adverse events.

  7. To evaluate the safety of topical BETA-TT8 based on TEAEs.

    Time frame: 12 weeks

    • Severity 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.

  8. To evaluate the safety of topical BETA-TT8 based on TEAEs.

    Time frame: 12 weeks

    • Relationship 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.

Secondary outcomes

  1. To further characterise ocular safety following repeated topical administration based on preliminary biological activity data.

    Time frame: 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.

  2. Exploratory-efficacy signals during BETA-TT8 treatment phase.

    Time frame: 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.

  3. Exploratory-efficacy signals during BETA-TT8 treatment phase.

    Time frame: 12 weeks

    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.

  4. Exploratory-efficacy signals during BETA-TT8 treatment phase.

    Time frame: 12 weeks

    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.

  5. To further characterise ocular safety following repeated topical administration based on preliminary biological activity data.

    Time frame: 12 weeks

    Based on Optical Coherence Tomography (OCT)-derived anatomical measures, including:

    • Mean change from baseline in Best Corrected Visual Acuity (BCVA) at each scheduled visit.

Other outcomes

  1. To assess systemic exposure effects of BETA-TT8 over the Extension Phase

    Time frame: 12 months

    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.

  2. To assesses potential efficacy of BETA-TT8 over the Extension Phase

    Time frame: 12 months

    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.

  3. To characterise aflibercept injection burden over the 12-month Extension Phase

    Time frame: 12 months

    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.

  4. To assesses potential efficacy of BETA-TT8 over the Extension Phase

    Time frame: 12 months

    At each scheduled visit during the Extension Phase, CST assessments will be performed as previously described.

  5. To assesses potential efficacy of BETA-TT8 over the Extension Phase

    Time frame: 12 months

    At each scheduled visit during the Extension Phase, intraretinal fluid/sub-retinal fluid (IRF/SRF) assessments will be performed as previously described.

  6. To assesses potential efficacy of BETA-TT8 over the Extension Phase

    Time frame: 12 months

    Patient reported outcomes will also be assessed at time points using the NEI-VFQ-25 questionnaire (National Eye Institute Visual Function Questionnaire-25).

  7. To assess systemic exposure effects of BETA-TT8 over the Extension Phase

    Time frame: 12 months

    Systemic exposure effects will be captured through fellow-eye (i.e. non-treated eye) safety assessment, measuring mean change in CST from baseline to each scheduled visit.

  8. To assess systemic exposure effects of BETA-TT8 over the Extension Phase

    Time frame: 12 Months

    Systemic exposure effects will be captured through fellow-eye (i.e. non-treated eye) safety assessments measuring mean change in slit-lamp from baseline to each scheduled visit.

  9. To assess systemic exposure effects of BETA-TT8 over the Extension Phase

    Time frame: 12 months

    Systemic exposure effects will be captured through sparse plasma BETA-TT8 concentration at specified scheduled visits.

Study contacts

Contact information is provided by the study sponsor or research team.

Hemal Mehta, MBBS MD, FRCOphth FRANZCO

CONTACT

[email protected]

(02) 4325 2482

Sarrvesa Singh

CONTACT

[email protected]

(02) 4325 2482

Sponsors and collaborators

Lead sponsor

Filamon LTD

Industry

Registry information

Official study title

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)

Acronym: BEyOND

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Aug 14, 2026
Registry last updated
Aug 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.