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)
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 24
- 试验地点
- 4
- 主要终点
- To evaluate the safety of topical BETA-TT8 based on TEAEs.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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-TT
- •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.
研究组 & 干预措施
BETA-TT8 Ophthalmic topical gel - Group two
One drop, twice daily
干预措施: BETA-TT8 ophthalmic gel 3.8% w/v (Drug)
BETA-TT8 Ophthalmic topical gel - Group one
One drop, once daily
干预措施: BETA-TT8 ophthalmic gel 3.8% w/v (Drug)
BETA-TT8 Ophthalmic topical gel - Group three
One drop, three times daily
干预措施: BETA-TT8 ophthalmic gel 3.8% w/v (Drug)
结局指标
主要结局
To evaluate the safety of topical BETA-TT8 based on TEAEs.
时间窗: 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.
时间窗: 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.
时间窗: 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.
时间窗: 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.
时间窗: 12 weeks
Incidence of corneal epithelial defects/staining abnormalities graded per National Eye Institute (NEI) or Oxford scale.
To evaluate the tolerability of topical BETA-TT8 based on reasons for discontinuations.
时间窗: 12 weeks
Incidence of treatment discontinuations due to adverse events.
次要结局
- To further characterise ocular safety following repeated topical administration based on preliminary biological activity data.(12 weeks)
- Exploratory-efficacy signals during BETA-TT8 treatment phase.(12 weeks)