A Randomized, Controlled, Double-Masked Evaluation of the Safety and Preliminary Efficacy of IVMED-80 on Keratoconus Progression
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Mean Maximum Central Keratometry (Kmax)
研究概览
简要总结
We investigated the use of a copper sulfate eye drop (IVMED-80) for the treatment of keratoconus. Preliminary laboratory data shows that the addition of copper sulfate increase crosslinking of the structural proteins of the cornea thereby halting the progressing corneal thinning and bulging seen in keratoconus. We conducted a Phase 1/2a study to evaluate the safety and preliminary efficacy of a 6-week and a 16-week regimen using IVMED-80 and studied its impact on ocular safety and the change/progression in patients' vision and clinical measurements.
详细描述
Standard Operating Procedures:
This study was designed to evaluate the safety and preliminary efficacy of IVMED-80 (0.15 mg/mL copper sulfate pentahydrate) in controlling the progression of corneal changes which typically occur in keratoconus patients.
This was a randomized, double-masked, placebo-controlled, and single-site clinical trial with eligible patients randomly assigned to one of three treatment groups:
- Group 1 (IVMED-6Wk) received topical copper sulfate eye drops 2x/day (BID) for 6 weeks and followed by an additional 20 weeks without treatment (total 26 weeks).
- Group 2 (IVMED-16Wk) received topical copper sulfate eye drops BID for 16 weeks and followed for an additional 10 weeks without treatment (total 26 weeks).
- Group 3 (Placebo) received IVMED-80 vehicle eye drops BID for 16 weeks and followed for an additional 10 weeks without treatment (total 26 weeks).
All patients were seen at Screening Visit, at Day 0 (Dispensing), and on Weeks 1, 3, 6, 12, 16, 21 and 26. In-office ophthalmology examinations used marketed medical diagnostic devices and routine clinical procedures. If a patient presents with two eyes meeting the eligibility criteria, the eye with the worst keratoconus based on maximum keratometry was selected as the Study Eye.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The investigational products, IVMED-80 or Placebo (IVMED-80 vehicle solution) eye drops, were masked to all sponsor and site personnel with the exception of those directly involved with the production, labeling and shipping of product to the study sites. During the study, the identity of the test articles and randomization were not revealed. An unmasked study coordinator managed test article receipt, dispensing and inventory at the study site. Investigators who interacted with study patients to assess safety and efficacy were masked as to the identity of the test articles and treatment group assignments.
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
- •Mild to moderate keratoconus and/or corneal ectasia post-LASIK or Photo-Refractive Keratectomy
- •Age 18 to 40
- •Minimum corneal thickness of > 350 microns
- •Maximum corneal keratometry of 45 D to 67 D
- •Absence of systemic comorbidities that pose a significant surgical risk
- •Absence of ocular comorbidities
- •Willing and able to comply with clinic visits and study-related procedures.
- •Provide signed informed consent
排除标准
- •Significant central corneal scarring or hydrops
- •Previous corneal surgeries
- •Presence of pre-existing glaucoma, uveitis, uncontrolled diabetic retinopathy, or prior ocular trauma or prior intraocular surgery.
- •Myopic degeneration with potential acuity less than 20/40 in the Study Eye.
- •Down's Syndrome, retinitis pigmentosa, Ehlers-Danlos Syndrome, osteogenesis imperfecta (or other collagen disorder) or Anton's Syndrome.
- •Prior retinal detachment involving the macula
- •Received a sub-Tenon's injection of corticosteroid within the past 6 months, or any intravitreal injection within the past 6 months in the study eye prior to Visit 1
- •Current use, or anticipated initiation during the study, of a systemic corticosteroid or an immunosuppressant agent by any route (oral, injectables)
- •History or current condition of substance or alcohol abuse within the past year
- •Participation in a clinical trial with use of any investigational drug or treatment within 30 days prior to Visit 1
- •Employee of the study site or their immediate families.
- •Pregnancy or planning to become pregnant.
研究组 & 干预措施
IVMED-6Wk
In Group 1 (IVMED-6Wk), patients instilled IVMED-80 eye drops into their study eye twice a day for 6 weeks and were followed for an additional 20 weeks without treatment (total 26 weeks)
干预措施: IVMED-80 (Drug)
IVMED-16Wk
In Group 2 (IVMED-16Wk), patients instilled IVMED-80 eye drops into their study eye twice a day for 16 weeks and were followed for an additional 10 weeks without treatment (total 26 weeks)
干预措施: IVMED-80 (Drug)
Placebo
In Group 3 (Placebo), patients instilled IVMED-80 vehicle solution eye drops into their study eye twice a day for 16 weeks and were followed for an additional 10 weeks without treatment (total 26 weeks)
干预措施: Placebo (Other)
结局指标
主要结局
Mean Maximum Central Keratometry (Kmax)
时间窗: 26 weeks
Change in maximum central keratometry after the assigned treatment was compared with baseline measures. This will be evaluated with and without z-score imputation. It will also be evaluated with a linear mixed effects model.
Number of Treatment-Emergent Adverse Events
时间窗: 26 Weeks
Treatment-emergent adverse events (TEAEs) were defined as events requiring additional treatments or cessation of the study article for which the date of onset was on or after the date of first dose of double-masked study drug at Day 0.
Mean Best Corrected Distance Visual Acuity (BCVA)
时间窗: 26 Weeks
Change in BCVA after the assigned treatment was compared with baseline measures.
次要结局
- Mean Posterior Maximum Corneal Elevation(26 Weeks)
- Mean Endothelial Cell Count (ECC)(26 Weeks)
- Percentage of patients with discomfort and redness upon instillation(26 Weeks)
- Mean Corneal hysteresis(26 weeks)
- Mean Corneal resistance factor (CRF)(26 weeks)
- Mean Central Corneal Thickness (CCT)(26 weeks)
- Mean Minimal Corneal Thickness(26 weeks)
- Mean Intraocular Pressure (IOP)(26 weeks)
- Mean Corneal Astigmatism(26 Weeks)
- Mean Central Keratometry (Kmean)(26 Weeks)
- Mean Uncorrected Visual Acuity (UCVA)(26 Weeks)
- Mean Stiffness parameter highest concavity (SP-HC)(26 Weeks)
- Mean Stress-strain index (SSI)(26 Weeks)
- Mean Peak distance(26 Weeks)