A Multi-Center, Open-Label, Single Ascending Dose Study To Assess the Safety, Tolerability, and Serum Pharmacokinetics of Intravitreal CLG561 in Subjects With Advanced Age-Related Macular Degeneration
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 50
- 主要终点
- Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, and serum pharmacokinetics of CLG561 in subjects with advanced age-related macular degeneration (AMD).
详细描述
Subjects were divided into 5 cohorts, with the subjects in each cohort being administered a single IVT dose of CLG561 in 1 of 5 concentration levels A-E, where A=lowest and E=highest. All subjects received active CLG561. Progress from one cohort to the next was time-lagged to allow for safety review. Dosing was also time-lagged within each cohort. Only one eye (designated as the study eye) was dosed per subject. Post-dose safety assessments and ocular examination occurred immediately after the IVT injection and continued throughout the outpatient visits at pre-determined timepoints. Collection of post-injection blood samples began after the IVT injection at pre-determined timepoints. Subjects were followed for up to 84 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of age-related macular degeneration in study eye, as specified in protocol.
- •Poor visual acuity in study eye, as specified in protocol.
- •Willing to receive meningitis and pneumonia vaccinations at least 2 weeks prior to study treatment.
- •Females must be post-menopausal and/or surgically sterile.
- •Other protocol-defined inclusion criteria may apply.
排除标准
- •Treatments to the study eye within 28 days prior to study treatment, as specified in protocol.
- •Any disease or medication expected to cause systemic or ocular immunosuppression.
- •Participation in another interventional clinical study or use of any experimental treatment for AMD within 12 weeks prior to study treatment.
- •Other protocol-defined exclusion criteria may apply.
研究组 & 干预措施
CLG561, Concentration Level A
Single 50 μL intravitreal injection of CLG561, Dose Level A
干预措施: CLG561 (Drug)
CLG561, Concentration Level B
Single 50 μL intravitreal injection of CLG561, Dose Level B
干预措施: CLG561 (Drug)
CLG561, Concentration Level C
Single 50 μL intravitreal injection of CLG561, Dose Level C
干预措施: CLG561 (Drug)
CLG561, Concentration Level D
Single 50 μL intravitreal injection of CLG561, Dose Level D
干预措施: CLG561 (Drug)
CLG561, Concentration Level E
Single 100 μL intravitreal injection of CLG561, Dose Level E
干预措施: CLG561 (Drug)
结局指标
主要结局
Number of Subjects With a Change From Normal to Abnormal in Ocular Signs at Any Post-Therapy Visit as Compared to Baseline Assessment
时间窗: Baseline, Day 2, Day 4, Day 8, Day 15, Day 29, Day 57, Day 85
A slit-lamp biomicroscopy examination was performed to evaluate the anterior segment of the eye. Subjects having a normal baseline evaluation were examined at subsequent visits, and any change from normal to abnormal was recorded. Criteria for reclassifying from normal to abnormal were left to the opinion of the investigators. One eye (study eye) contributed to the analysis. None of the abnormalities were deemed related to the study medication.
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) by Visit - Study Eye
时间窗: Baseline, Day 2, Day 4, Day 15, Day 29, Day 57, Day 85
BCVA (with spectacles or other visual corrective devices) using Early Treatment Diabetic Retinopathy Study (ETDRS) testing was reported in letters read correctly. Improvement of BCVA was defined as an increase (gain) in letters read from the baseline assessment. One eye (study eye) contributed to the analysis.
Mean Intra-Ocular Pressure (IOP) by Visit - Study Eye
时间窗: Baseline, Day 1, Day 2, Day 4, Day 15, Day 29, Day 57, Day 85
IOP was measured by Goldmann applanation tonometry or tonopen, at the discretion of the Investigator, and reported in mmHg (millimeters of mercury). A higher IOP can be a greater risk factor for developing glaucoma or glaucoma progression (leading to optic nerve damage). One eye (study eye) contributed to the analysis.
Number of Subjects With Change From Normal to Abnormal in Fundus Examination at Any Post-Therapy Visit as Compared to Baseline Assessment
时间窗: Baseline, Day 2, Day 4, Day 8, Day 15, Day 29, Day 57, Day 85
A dilated fundus examination was performed to evaluate the health of the retina, macula, choroid, and optic nerve. Subjects having a normal baseline evaluation were examined at subsequent visits, and any change from normal to abnormal was recorded. Criteria for reclassifying from normal to abnormal were left to the opinion of the investigators. One eye (study eye) contributed to the analysis. None of the abnormalities were deemed related to the study medication.
次要结局
- Area Under the Serum Concentration-time Curve (AUC) From Time Zero to All [AUC(0-all)](Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85)
- Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)](Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85)
- Time to Reach the Maximum Serum Concentration After Drug Administration (Tmax)(Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85)
- Dose Normalized Observed Maximum Serum Concentration Following Drug Administration (Cmax/D)(Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85)
- Dose-normalized Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC(0-last)/D](Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85)
- Area Under the Serum Concentration-time Curve From Time Zero to Time "t" Where t is a Defined Time Point After Administration [AUC(0-t)](Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85)
- Terminal Elimination Half-life (T½)(Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85)
- The Apparent Volume of Distribution During the Terminal Elimination Phase Following Extravascular Administration (Vz/F)(Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85)
- Apparent Systemic (or Total Body) Clearance From Serum Following Extravascular Administration (CL/F)(Day 1 pre-injection, 2h, 6h, Day 2, Day 4, Day 6, Day 8, Day 11, Day 15, Day 29, Day 57, Day 85)