A Randomized, Double Masked, Three Dose Safety and Pharmacokinetic Study of RTH258 Following Intravitreal (IVT) Injection in Subjects With Neovascular Age-Related Macular Degeneration
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 51
- 主要终点
- Maximum Analyte Serum Concentration [Cmax (ng/mL)]
研究概览
简要总结
The purpose of this study is to assess the systemic pharmacokinetics (PK) and safety of 2 different doses of brolucizumab (3 milligrams (mg)/50 microliters (μL) and 6 mg/50 μL) when administered at 4-week intervals for a total of 3 intravitreal injections in subjects with neovascular age-related macular degeneration (AMD).
详细描述
This study has 2 arms with a 1:1 randomization. Randomization will be stratified by Japanese ethnicity. Half of the subjects in each arm will be of Japanese ethnicity. The other half of the subjects in each arm will be non-Japanese. Subjects in both arms will have visits at Screening, Day 0 (Baseline), Day 1 (24 hours post first injection), Day 3, Day 14, Day 21, Day 28, Day 56, Day 57 (24 hours post the injection on Day 56) and Day 84.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
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
- •Provide written informed consent;
- •Active choroidal neovascularization (CNV) lesions secondary to AMD that affect the central subfield in the study eye;
- •Best Corrected Visual Acuity (BCVA) > 23 letters in the study eye at Baseline;
- •50 years of age or older at the time of Screening.
排除标准
- •Any active ocular infection or inflammation;
- •Treatment with aflibercept (EYLEA®), bevacizumab (AVASTIN®), ranibizumab (LUCENTIS®), brolucizumab, or an investigational drug for neovascular AMD prior to enrollment in the study, as specified in protocol;
- •Ocular surgery in the study eye, as specified in protocol;
- •Uncontrolled glaucoma in the study eye, as specified in protocol;
- •Use of steroids in the study eye, as specified in protocol;
- •Medical conditions that may prevent study completion;
- •Pregnant or nursing (lactating) women;
- •Women of child-bearing potential unless using contraception;
- •Uncontrolled blood pressure, as specified in protocol;
- •Other protocol-specified exclusion criteria may apply.
研究组 & 干预措施
Brolucizumab 3 mg
Brolucizumab 3 mg/50 μL administered as an intravitreal injection 3 times at 4-week intervals with follow-up for 84 days from the initial injection
干预措施: Brolucizumab 3 mg/50 μL (Drug)
Brolucizumab 6 mg
Brolucizumab 6 mg/50 μL administered as an intravitreal injection 3 times at 4-week intervals with follow-up for 84 days from the initial injection
干预措施: Brolucizumab 6 mg/50 μL (Drug)
结局指标
主要结局
Maximum Analyte Serum Concentration [Cmax (ng/mL)]
时间窗: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Elimination Half-life in Serum [t1/2 (h)]
时间窗: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Time to Reach Maximum Analyte Serum Concentration [Tmax (h)]
时间窗: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Concentration of RTH258 Obtained 24 Hours Post Day 0 Injection [C24hr (ng/mL)]
时间窗: Day 1
Serum concentration at the specified collection time point was quantitated, where possible, using a validated immunoassay method. The data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration [AUC0-tlast (ng*h/mL)]
时间窗: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Area Under the Concentration-time Curve From 0 to Infinity [AUC0-inf (ng*h/mL)]
时间窗: Day 0 (predose), 6 hr, 24 hr, 72 hr, 168 hr, 336 hr, 504 hr, 672 hr
Serum concentrations at each collection time point were quantitated, where possible, using a validated immunoassay method. These data were analyzed using a noncompartmental pharmacokinetic (PK) method.
Concentration of RTH258 Obtained 24 Hours Post Day 56 Injection [C24hr (ng/mL)]
时间窗: Day 57
Serum concentration at the specified collection time point was quantitated, where possible, using a validated immunoassay method. The data were analyzed using a noncompartmental pharmacokinetic (PK) method.
次要结局
- Percentage of Subjects With Positive Anti-drug Antibody (ADA) Status (Test)(Day 0 (predose), Day 28, Day 84)