A Phase 1 Open-Label, Dose Escalation Study to Assess the Safety and Tolerability of Intravitreal ONL1204 in Patients With Macula-off, Rhegmatogenous Retinal Detachment
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 4
- 主要终点
- Adverse Event (AE) Reporting
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of ONL1204 in participants with Macula-off, Rhegmatogenous Retinal Detachment (RRD). RRD is an acute and serious vision threatening condition in which a tear in the retina, typically resulting from a vitreous detachment, allows liquid to accumulate under the retina, detaching the photoreceptor (PR) layer of the retina from the retinal pigment epithelium (RPE). As the RPE is the principal source of nutritional support for the PR layer, the photoreceptors begin a cascade of inflammation and cell death. Photoreceptor cell death is the primary mechanism of vision loss after retinal detachment.
ONL1204 is a first-in-class inhibitor of Fragment Apoptosis Stimulator receptor (Fas)-mediated cell death. ONL1204 has demonstrated protection of multiple retinal cell types in numerous preclinical models of acute ocular injury. This will be a first-in-human (FIH) study to evaluate safety and tolerability of a single-dose of ONL1204 in participants with macula-off RRD. The standard of care for surgical repair of macula-off RRD is reattachment surgery within 7 days of the macula detaching. Participants in this study will receive a single intravitreal injection upon diagnosis and enrollment in the study, followed by standard of care surgery. The surgery includes vitrectomy, a procedure that removes the bulk of drug remaining in the vitreous.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females, ≥ 18 to 80 years old
- •Able to give informed consent and comply with all study visits and procedures
- •Patients who:
- •Present between 1 week (7 days) and 4 weeks (28 days) of a macula-off RRD (based on patient-reported history of loss of central vision)
- •For whom standard retinal reattachment surgery by means of a pars plana vitrectomy (with or without scleral buckle) and gas tamponade is indicated, and
- •In the opinion of the investigator, can safely undergo all study procedures.
- •Best corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity of 20/100 to hand motion in the study eye
- •Best corrected ETDRS visual acuity in the fellow eye of 20/60 or better
排除标准
- •Presence of giant retinal tear defined as greater than 3 clock hours or other type of complex retinal detachment in the study eye
- •Presence of vitreous hemorrhage in the study eye
- •Presence of ocular or periocular infection or intraocular inflammation in either eye
- •Intraocular Pressure > 22 mmHg in the study eye
- •Any other significant ocular disease in the study eye including media opacity that, in the opinion of the investigator, would preclude a visual acuity of at least 20/25 following successful vitrectomy or limit adequate visibility of the retina
- •Any other ocular pathology in the study eye requiring treatment with topical ophthalmic drops or intravitreal injection
- •History of previous ocular surgery in the study eye other than uncomplicated cataract surgery with posterior chamber intraocular lens and intact posterior capsule (which must have occurred at least 6 months prior to the baseline visit)
- •Participation in other clinical trials or use of any other investigational drugs or devices within 3 months prior to study participation
- •Females who are pregnant or lactating and women of childbearing potential who are not using adequate contraceptive precautions (e.g., intrauterine device, oral contraceptives, barrier method, or other contraception deemed adequate by the investigator)
- •Known retinopathy, known hepatic disease (or history of significant chronic liver disease), or known renal disease. Patients with diabetes and no known retinopathy may be enrolled
- •History of uncontrolled hypertension
- •History of stroke, transient ischemic attack, or major cardiac surgery within 3 months prior to study, or current treatment for systemic infection
- •Any ocular or systemic condition that in the opinion of the investigator could compromise the safety of the patient, or may interfere with the safety and tolerability assessments or study procedures of the trial
研究组 & 干预措施
Cohort 1 Dose A
Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 1
干预措施: ONL1204 (Drug)
Cohort 1 Dose A
Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 1
干预措施: Intravitreal Injection (Procedure)
Cohort 1 Dose A
Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 1
干预措施: Collection of ocular fluids (Procedure)
Cohort 2 Dose B
Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 2
干预措施: ONL1204 (Drug)
Cohort 2 Dose B
Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 2
干预措施: Intravitreal Injection (Procedure)
Cohort 2 Dose B
Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 2
干预措施: Collection of ocular fluids (Procedure)
Cohort 3 Dose C
Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 3
干预措施: ONL1204 (Drug)
Cohort 3 Dose C
Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 3
干预措施: Intravitreal Injection (Procedure)
Cohort 3 Dose C
Intravitreal injection of 50 μl of ONL1204 liquid formulation to deliver dose 3
干预措施: Collection of ocular fluids (Procedure)
Cohort 4 Dose D
Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 4
干预措施: ONL1204 (Drug)
Cohort 4 Dose D
Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 4
干预措施: Intravitreal Injection (Procedure)
Cohort 4 Dose D
Intravitreal injection of 100 μl of ONL1204 liquid formulation to deliver dose 4
干预措施: Collection of ocular fluids (Procedure)
结局指标
主要结局
Adverse Event (AE) Reporting
时间窗: 24 weeks
AEs restricted to treatment-emergent AEs (TEAEs) only. Ocular and non-ocular AEs reported separately. See AE Reporting Table for descriptive ocular and non-ocular AE findings.
BCVA (LogMAR) at Final Study Visit
时间窗: 24 weeks
BCVA was performed in the study eye using ETDRS methodology and letters read were converted to a logMAR value using the following equation: logMAR = -0.02 × ETDRS + 1.7.
次要结局
未报告次要终点