A Prospective First-In-Human Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa (adRP) Due to the P23H Mutation in the RHO Gene
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 11
- 试验地点
- 5
- 主要终点
- Incidence and Severity of non-ocular AEs
研究概览
简要总结
This study evaluates the safety, tolerability and efficacy of QR-1123 injection in the eye (intravitreal; IVT) injections (one eye/unilateral) in subjects receiving a single dose or repeat doses. Single injections will be assessed in an open label way, and repeat injections will be assessed in a double-masked, randomized, sham-controlled fashion.
详细描述
QR-1123 is an antisense oligonucleotide, designed to specifically target the mutant P23H messenger ribonucleic acid (mRNA) in order to reduce the expression of the P23H protein selectively, while preserving expression of the wild type (WT) rhodopsin (RHO) protein. It is hypothesized that the reduction of mutant P23H mRNA will reduce the deleterious effects of the dominant-negative protein and should result in increased function of WT rhodopsin protein in photoreceptors. Restoration of WT RHO function is expected to improve vision in patients with adRP due to the P23H mutation.
The study will comprise up to 8 single dose and repeat dose cohorts. Prior to initiating a higher single dose cohort and/or prior to initiating repeat dose cohort(s), available safety and efficacy data will be reviewed by the DMC.
In the single dose cohorts subjects will receive a single, unilateral IVT injection of QR-1123 in an open label fashion. In the repeat dose cohorts subjects will be randomized to receive either a unilateral IVT injection of QR-1123 every 3 months or a unilateral sham procedure every 3 months, in a double masked fashion. Subjects will be followed for safety, tolerability and efficacy for a total period of 12 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
盲法说明
Single dose cohorts are open label. Repeat dose cohorts are randomized, double masked.
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
- •Male or female, ≥ 18 years of age.
- •Clinical presentation consistent with adRP, based on ophthalmic examinations.
- •Impairment on VF in the opinion of the Investigator, as determined by perimetry.
- •A molecular diagnosis of autosomal dominant form of RP with the P23H mutation in the RHO gene, based on genetic analysis.
- •A clear ocular media and adequate pupillary dilation to permit good quality fundus imaging, as assessed by the Investigator.
排除标准
- •Presence of additional pathogenic mutations in genes (other than the P23H mutation in the RHO gene) associated with inherited retinal degenerative diseases or syndromes, based on genetic analysis (eg, Usher syndrome, Leber congenital amaurosis, etc).
- •Presence of any significant ocular or non-ocular disease/disorder (including medication and laboratory test abnormalities) which, in the opinion of the Investigator and with concurrence of the Medical Monitor, may either put the subject at risk because of participation in the study, may influence the results of the study, or the subject's ability to participate in the study.
研究组 & 干预措施
QR-1123 Single dose - dose level 1
Open label Single dose cohort: dose level 1
干预措施: QR-1123 (Drug)
QR-1123 Single dose - dose level 2
Open label Single dose cohort: dose level
干预措施: QR-1123 (Drug)
QR-1123 Single dose - dose level 3
Open label Single dose cohort: dose level 3
干预措施: QR-1123 (Drug)
QR-1123 Single dose - dose level 4
Open label Single dose cohort: dose level 4
干预措施: QR-1123 (Drug)
QR-1123 Single dose - dose level 5
Open label Single dose cohort: dose level 5
干预措施: QR-1123 (Drug)
Repeat dose cohort 1
Double-masked, randomized, sham controlled, Repeat dose cohort. Dose levels will be determined following DMC review of obtained safety and efficacy data.
干预措施: QR-1123 (Drug)
Repeat dose cohort 1
Double-masked, randomized, sham controlled, Repeat dose cohort. Dose levels will be determined following DMC review of obtained safety and efficacy data.
干预措施: Sham procedure (Other)
结局指标
主要结局
Incidence and Severity of non-ocular AEs
时间窗: up to 12 months
Incidence and severity of non-ocular adverse events scored based on CTCAC in the study and fellow eye
Incidence and Severity of ocular AEs
时间窗: up to 12 months
Incidence and severity of ocular adverse events scored based on CTCAC in the study and fellow eye
次要结局
- Changes in DAC perimetry(up to 12 months)
- Changes in Static VF(up to 12 months)
- Assessment of systemic exposure after treatment with QR-1123(up to 12 months)
- Changes in BCVA(up to 12 months)
- Changes in LLVA(up to 12 months)
- Changes in Microperimetry(up to 12 months)
- Changes in SD-OCT(up to 12 months)
- Changes in FST(up to 12 months)
- Changes in Full-field ERG(up to 12 months)