A Proof of Concept, Open-label, Two-arm Study to Investigate the Safety and Preliminary Efficacy of TN-001 Topical Eyedrops in Male and Female Patients With Progressive Keratoconus.
试验速览
- 阶段
- 1 期
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Participant-reported ocular tolerability score (5-point scale)
研究概览
简要总结
The goal of this clinical trial is to learn if TN-001, a new eye-drop therapy, is safe and well-tolerated in adult patients with progressive keratoconus. It will also provide data on whether this therapy is effective in treating keratoconus.
The main questions it aims to answer are:
What medical problems do participants have when using TN-001 eyedrops? Does TN-001 eyedrop therapy stop keratoconus from progressing further?
Participants will:
Take TN-001 eyedrops twice a day, every day, for 3-6 weeks. Visit the clinic once every week for checkups and tests. Keep a diary of their symptoms.
详细描述
TN-001, the study drug, is a topical eyedrop containing Transforming Growth Factor Beta 3 (TGFB3) and Dexamethasone Sodium Phosphate (DexSP). It is anticipated that TN-001 may produce collagen in the eye, which is believed to stiffen the cornea. Stiffening of the cornea is desirable in patients with keratoconus as it helps to stop disease progression.
The purpose of this study is to:
- Evaluate the safety of TN-001
- Evaluate whether TN-001 eye drops are well tolerated in and around the eye
- Provide an initial indication on whether TN-001 may be effective in treating progressive keratoconus.
- Provide an indication of the duration of treatment impact.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must be 18 to 40 years of age inclusive, at the time of signing the informed consent.
- •Diagnosed with progressive keratoconus in one or both eyes.
- •Minimum corneal thickness equal to or greater than 400 microns.
- •Maximum corneal keratometry of 45 D to 54 D.
- •Willing and able to comply with all clinic visits and study-related procedures and instructions.
- •Able to self-medicate or be assisted with applying study eye drops twice daily for trial duration.
- •Provide signed informed consent to participate in the study.
排除标准
- •Concurrent use of contact lenses, including rigid gas permeable lenses
- •Known allergy to steroids, growth factors or gellan gum
- •Presence of ocular surface inflammation at any screening visit
- •Recurrent corneal erosions
- •Significant central corneal scarring or hydrops
- •Previous corneal cross-linking
- •Previous corneal transplant
- •Previous corneal or intraocular surgeries
- •Presence of any other ocular disease of the eye (not limited to cornea) e.g. glaucoma, uveitis, uncontrolled diabetic retinopathy
- •Presence or history of ocular cancer
- •Prior ocular trauma or prior retinal detachment involving the macula
- •Received an ocular corticosteroid within the past 6 months (within the past 3 months, for topical ocular corticosteroids), or any intravitreal injection within the last 6 months in the study eye prior to day 0
- •Any severe comorbid condition or other issue that renders the participant unsuitable for participation in the study
- •A comorbid condition with an estimated life expectancy of ≤6 months at the time of consent
- •Systemic comorbidities that pose a significant surgical risk
- •Current use or anticipated use during the study of a systemic corticosteroid with a dose greater than 10mg daily, or an immunosuppressant agent by any route (oral, injectable)
- •Current use or anticipated use during the study of medicated lubricating eye drops or topical ophthalmic antihistamines
- •History of connective tissue disorders, collagenoses, collagen vascular diseases, autoimmune or other immune deficiency disease
- •Pregnancy or planning to become pregnant
- •Participation in another interventional clinical trial within 30 days or 5 half-lives of that Investigational Product prior to consent for this trial, or planning to participate in another clinical trial at the time of consent
- •Known alcohol, drug or medication abuse within 1 year prior to consent for this study
- •Treatment with an anticancer therapy (chemotherapy, immunotherapy, radiotherapy, targeted therapy or gene therapy) within 3 months prior to day 0 or at any time during the study. Recovery from any associated toxicities must be documented prior to inclusion
- •Mental condition rendering the participant unable to understand the nature, scope, and possible consequences of the study
- •Participants who are employees of the Sponsor, study site or their immediate families
- •Inability or unwillingness to comply with all follow-up through to the end of the study, and/or unwilling to allow access to review medical records in accordance with local regulatory requirements at the time of consent
- •Retinal disease, including proliferative diabetic retinopathy, retinal fibrosis, neovascular age-related macular degeneration
- •Participants in whom corneal thinning has stabilized by ophthalmologist's opinion during screening
- •Myopic degeneration with potential acuity less than 20/40 in either eye
- •Any reason for which in the opinion of the principal investigator the participant should not be enrolled into the study
研究组 & 干预措施
Low-dose
Low dose TGF-B3 and Dexamethasone Sodium Phosphate
干预措施: Low-dose TGF-B3 and Dexamethasone Sodium Phosphate (Drug)
High-dose
High dose TGF-B3 and Dexamethasone Sodium Phosphate
干预措施: High-dose TGF-B3 and Dexamethasone Sodium Phosphate (Drug)
结局指标
主要结局
Participant-reported ocular tolerability score (5-point scale)
时间窗: Baseline (Day 1) to Day 180 of treatment initiation
Participant-reported ocular tolerability was assessed using a study-specific eye questionnaire measured on a 5-point ordinal scale in the treatment eye.
Incidence of ocular and peri-ocular inflammation by slit-lamp examination
时间窗: Baseline (Day 1) through Day 180
Incidence of inflammation of the eye and surrounding tissues, including redness, aqueous cells, flare, limbus, fornices, tear ducts, and meibomian glands, assessed by slit-lamp microscopy using the Efron scale or a similar numerical grading scale in the treatment eye.
Incidence of corneal scarring and conjunctival inflammation
时间窗: Baseline (Day 1) through Day 180
Incidence of corneal scarring and conjunctival inflammation assessed by slit-lamp microscopy using the Efron scale or a similar numerical grading scale in the treatment eye.
Increase from baseline in intraocular pressure (mmHg)
时间窗: Baseline (Day 1) through Day 180
Increase from baseline in intraocular pressure measured using a hand-held tonometer (mmHg) in the treatment eye.
Change from baseline in endothelial cell count (cells/mm²)
时间窗: Baseline (Day 1) through Day 180
Change from baseline in endothelial cell count measured using specular microscopy (cells/mm²) in the treatment eye.
Change from baseline in endothelial cell characteristics
时间窗: Baseline (Day 1) through Day 180
Change from baseline in endothelial cell characteristics, including coefficient of variation and percentage of hexagonal cells, measured using specular microscopy in the treatment eye.
Incidence of structural corneal and ocular surface changes
时间窗: Baseline (Day 1) through Day 180
Incidence of structural changes of the cornea and ocular surface, including corneal opacities, corneal haze, and keratitis, assessed by anterior segment optical coherence tomography in the treatment eye.
Change from baseline in stromal thickness (microns)
时间窗: Baseline (Day 1) through Day 180
Change from baseline in stromal thickness measured in microns using anterior segment optical coherence tomography in the treatment eye.
Change from baseline in choroidal and retinal thickness
时间窗: Baseline (Day 1) through Day 180
Change from baseline in choroidal and retinal thickness measured using optical coherence tomography in the treatment eye.
Incidence of abnormal findings on dilated fundus examination
时间窗: Baseline (Day 1) through Day 180
Incidence of pathology involving the retina, optic nerve, lens, and/or macula assessed by dilated fundus examination using slit-lamp microscopy with a fundus lens in the treatment eye.
Change from baseline in visual acuity (LogMAR)
时间窗: Baseline (Day 1) through Day 180
Change from baseline in visual acuity measured using a LogMAR chart in the treatment eye.
次要结局
- Change from baseline in corneal stiffness and biomechanics(Baseline (Day 1) to Day 180 of treatment initiation)
- Change from baseline in maximum corneal curvature (Kmax)(Baseline (Day 1) through Day 180)
- Change from baseline in mean central corneal curvature(Baseline (Day 1) through Day 180)
- Change from baseline in corneal thickness (pachymetry)(Baseline (Day 1) through Day 180)
- Change from baseline in corneal shape (Belin ABCD parameters)(Baseline (Day 1) through Day 180)
- Change from baseline in corneal higher-order aberrations(Baseline (Day 1) through Day 180)