A Multi-center, Non-Randomized, Open-label, Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7200220 in Monotherapy and in Combination With Ranibizumab Following Intravitreal Administration in Patients With Diabetic or Uveitic Macular Edema
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 85
- 试验地点
- 19
- 主要终点
- Part 1: Number of Participants With Adverse Events (AEs)
研究概览
简要总结
The purpose of this study was to assess the safety and tolerability of RO7200220 as monotherapy (diabetic macular edema [DME] or uveitic macular edema [UME] population) and in combination with ranibizumab (DME population only).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DME Participants:
- •Diagnosis of Diabetes Mellitus (DM) (Type 1 or Type 2), as defined by the World Health Organization and/or American Diabetes Association
- •Macular edema associated with DR defined as macular thickening by spectral domain optical coherence tomography (SD-OCT) involving the center of the macula: central subfield thickness (CST) of ≥325 μm with Spectralis.
- •Decreased visual acuity (VA) attributable primarily to DME, with BCVA letter score of 73 to 19 letters (both inclusive) on Early Treatment Diabetic Retinopathy Study (ETDRS)-like charts (20/40 -20/400 Snellen equivalent).
- •Clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images to confirm diagnosis.
- •UME Participants:
- •Diagnosis of noninfectious uveitis (NIU) of any anatomical type (anterior, intermediate, posterior, panuveitis). Active and inactive NIU is allowed.
- •Macular edema associated with NIU defined as macular thickening by SD-OCT involving the center of the macula: CST of ≥325 μm with Spectralis.
- •Decreased VA attributable primarily to UME, with BCVA letter score of 78 to 19 letters (both inclusive) on ETDRS-like charts (20/32 - 20/400 Snellen equivalent).
- •Sufficiently clear ocular media and adequate pupillary dilation to allow acquisition of good quality retinal images to confirm diagnosis.
- •Either treatment naive or previously treated in the study eye or systematically (with washout periods and maximum doses applicable for specific treatments).
排除标准
- •Any major illness or major surgical procedure within 1 month prior to Day 1
- •Any febrile illness within 1 week prior to screening or Day 1
- •Any stroke or myocardial infarction within 12 months prior to Day 1
- •Any active proliferative DR (DME participants only)
- •Panretinal photocoagulation or macular laser photocoagulation treatment prior to Day 1
- •History of vitreoretinal surgery/pars plana vitrectomy
- •Any cataract surgery within 3 months prior to Day 1 or any planned surgery during the study
- •History of any glaucoma surgery including laser glaucoma procedures
- •Uncontrolled glaucoma
- •History of rubeosis iridis
- •Any active ocular or periocular infection on Day 1
- •Any presence of active intraocular inflammation on Day 1 or any history of intraocular inflammation (DME participants only)
- •Any prior or concomitant periocular or IVT corticosteroids in the study eye (DME treatment naive participants only)
- •Use of any systemic corticosteroids within 1 month prior to Day 1 (stable oral prednisone for UME participants allowed)
- •Any prior or concomitant systemic anti-VEGF treatment within 6 months prior to Day 1
- •Any concurrent use of biologics for immune-related diseases
研究组 & 干预措施
Part 1: RO7200220 Monotherapy
Participants with DME received multiple ascending doses of RO7200220 (two doses at the assigned dose level), as intravitreal (IVT) injection, every 6 weeks (Q6W) in multiple cohorts.
干预措施: RO7200220 (Drug)
Part 2: Expansion of RO7200220 Monotherapy
Participants with DME who were anti-VEGF and corticosteroid IVT treatment-naive received three doses of RO7200220 monotherapy, as IVT injection, every 4 weeks (Q4W) in Part 2 cohorts.
干预措施: RO7200220 (Drug)
Part 3: RO7200220 in Combination with Ranibizumab
Participants with DME received RO7200220 as IVT injection followed by ranibizumab, 0.5 milligrams (mg) as IVT injection in Part 3.
干预措施: RO7200220 (Drug)
Part 3: RO7200220 in Combination with Ranibizumab
Participants with DME received RO7200220 as IVT injection followed by ranibizumab, 0.5 milligrams (mg) as IVT injection in Part 3.
干预措施: Ranibizumab (Drug)
Part 4: RO7200220 Monotherapy
Participants with UME received multiple doses of RO7200220 (three doses at the assigned dose level), as IVT injection, Q4W in multiple cohorts.
干预措施: RO7200220 (Drug)
结局指标
主要结局
Part 1: Number of Participants With Adverse Events (AEs)
时间窗: Up to 18 weeks
Part 2: Number of Participants With Adverse Events (AEs)
时间窗: Up to 24 weeks
Part 3: Number of Participants With Adverse Events (AEs)
时间窗: Up to 20 weeks
Part 4: Number of Participants With Adverse Events (AEs)
时间窗: Up to 36 weeks
次要结局
- Maximum Serum Concentration (Cmax)(Part 1: Up to Week 18; Parts 2: Up to Week 24; Part 3: Up to Week 20; Part 4: Up to Week 36)
- Minimum Serum Concentration (Ctrough)(Part 1: Up to Week 18; Parts 2: Up to Week 24; Part 3: Up to Week 20; Part 4: Up to Week 36)
- Time to Peak Serum Concentration (Tmax)(Part 1: Up to Week 18; Parts 2: Up to Week 24; Part 3: Up to Week 20; Part 4: Up to Week 36)
- Area Under the Concentration-time Curve to the End of Dosing Period (AUC0-t)(Part 1: Up to Week 18; Parts 2: Up to Week 24; Part 3: Up to Week 20; Part 4: Up to Week 36)