A Phase I/IIa Clinical Trial to Assess the Safety, Tolerability, and Efficacy of a Single Intravitreal Injection of SPVN20 Gene Therapy in Participants With Advanced Rod-Cone Dystrophy
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 27
- 试验地点
- 3
- 主要终点
- Safety and Tolerability
研究概览
简要总结
This open-label, multi-center study is to evaluate the safety, tolerability, and efficacy of escalating doses of a gene therapy called SPVN20 administered via a single intravitreal injection in participants with advanced Rod-Cone Dystrophy.
详细描述
This is an open-label, non-randomized, multi-center, dose-escalation and dose-expansion, first-in-human, Phase I/IIa study. Participants will be followed for a total of five years after receiving a single unilateral intravitreal injection of SPVN20 in their study eye, and will be monitored by an independent Data Safety Monitoring Committee. Eligible patients will be assigned by sequential enrollment to one of the following three cohorts:
Cohort 1: low dose of SPVN20 will be evaluated in a total of 9 participants. Cohort 2: medium dose of SPVN20 will be evaluated in a total of 9 participants. Cohort 3: high dose of SPVN20 will be evaluated in a total of 9 participants.
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
- •Age ≥ 18 years old at enrollment.
- •Participant with a genetically confirmed clinical diagnosis of advanced RCD in both eyes due to non-syndromic RCD.
- •Participants enrolled in the Dose-Escalation cohorts must have a BCVA meeting the study eye criteria.
- •Documented preservation of foveal cone cell bodies in the study eye (as shown on SD-OCT imaging).
- •Participant with a history of formed vision.
- •Participant willing and able to provide informed consent.
排除标准
- •Participant participating in another clinical trial and receiving an investigational medicinal product (IMP) within either 5 half-lives of that IMP, or 90 days prior to the injection of SPVN
- •Participant with cortical visual impairment.
- •Participant with systemic disease or other pathology not related to their diagnosis of RCD, and whose symptoms or associated treatments may affect vision.
- •Participant with known allergies to corticosteroids, or who will be unable to tolerate the corticosteroid regimen.
- •Participant who has received immunosuppressive therapies or any other therapy known to impact the immune system during the last month prior to SPVN20 administration.
- •Active ocular inflammation or recurrent history of idiopathic or autoimmune-associated uveitis.
- •Participant known to be allergic to any of the delivery vehicle constituents or to any other drugs planned to be used during the clinical study.
- •Active alcohol or substance abuse.
- •Participant positive for human immunodeficiency virus (HIV) or any other systemic immunocompromising disease.
- •Participant with active Hepatitis B or Hepatitis C.
- •Female participant currently pregnant or breastfeeding or intending to become pregnant.
- •Participant with clinically active ocular infection of herpetic diseases.
- •Participant with active coronavirus disease (COVID-19) infection.
- •Participant who received any vaccination/immunization within 28 days prior to screening and/or during screening.
- •Participant who previously received any gene therapy product, stem cell therapy, cell-based therapy for ocular or non-ocular disease.
- •Participant with a retinal implant at enrollment.
- •Participant with pre-existing eye conditions that would interfere with the interpretation of study endpoints, or increase the risk of surgical complications.
- •Participant with significant media opacity impacting evaluation of the retina or vitreous.
- •Participant who had intraocular surgery within 90 days of study treatment administration.
- •Participant with history of corticosteroid-induced raised IOP of >25 mmHg following corticosteroid exposure, despite topical IOP-lowering pharmacologic therapy.
- •Participant with history of unresolved rhegmatogenous retinal detachment in the fovea.
- •Participant with history of unresolved ocular hypotony.
- •Participant unwilling or unable (based on the Investigator's judgment) to comply with the study protocol.
- •Participant with any condition that would not allow them to complete follow-up examinations during the study and, in the opinion of the Investigator, would make them unsuitable for the study.
- •Participant currently taking restricted classes of medications listed in protocol
- •Participant with ongoing cardiac or neurological disorders not managed by a restricted medication can be excluded based on the Investigator's judgement.
- •Women of childbearing potential (WOCBP) and men and/or their partner(s) of childbearing potential who do not agree to use a highly effective contraceptive method.
研究组 & 干预措施
SPVN20 (low dose). Single intravitreal injection of a low dose of SPVN20 on Day 0
SPVN20
干预措施: SPVN20 (low dose) (Biological)
SPVN20 (medium dose). Single intravitreal injection of a medium dose of SPVN20 on Day 0
SPVN20
干预措施: SPVN20 (medium dose) (Biological)
SPVN20 (high dose). Single intravitreal injection of a high dose of SPVN20 on Day 0
SPVN20
干预措施: SPVN20 (high dose) (Biological)
结局指标
主要结局
Safety and Tolerability
时间窗: 6 months
Incidence and severity of ocular and non-ocular treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Ocular safety
时间窗: 6 months
General ocular assessments including complete ophthalmic examination of extraocular and intraocular structures
次要结局
- Best Corrected Visual Acuity (BCVA)(6 months)
- Full-field stimulus threshold (FST) test(6 months)