A Natural History and Outcome Measure Discovery Study of PRPF31 Mutation-Associated Retinal Dystrophy
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 50
- 试验地点
- 10
- 主要终点
- Change from Baseline in Ellipsoid Zone (EZ) Area
研究概览
简要总结
The purpose of this study is to characterize the natural history through temporal systemic evaluation of subjects identified with PRPF31 mutation-associated retinal dystrophy, also called retinitis pigmentosa type 11, or RP11.
Assessments will be completed to measure and evaluate structural and functional visual changes including those impacting patient quality of life associated with this inherited retinal condition and observing how these changes evolve over time.
详细描述
This is a multi-center, longitudinal, prospective observational natural history study of participants with a molecularly confirmed mutation in PRPF31. Approximately 50 participants (100 eyes) at approximately 5 sites will be enrolled into a uniform protocol for follow-up and evaluations. Each participant's medical record will be reviewed for historical information, and clinical data will be recorded in a secure database. Natural history data will be collected prospectively and will include ophthalmic exams, imaging studies, electrophysiological testing, functional mobility evaluations, and questionnaires. Assessments will be conducted in a standardized protocol every 16 weeks ± 4 weeks for the first year and then every 24 weeks ± 4 weeks for up to approximately 4 years after each participant's baseline visit (Visit 2).
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following in order to be enrolled into the study:
- •Male or female, ≥ 10 years of age at baseline (Visit 2).
- •Have a clinical and molecular diagnosis of PRPF31 mutation-associated retinal dystrophy.
- •If ≥ 18 years of age, understand the language of the informed consent and are willing and able to provide written informed consent prior to any study procedures. If < 18 years of age, are willing to assent to study participation in writing and have a legally authorized representative provide written informed consent on your behalf.
- •Are willing to comply with the instructions and attend all scheduled study visits.
排除标准
- •Participants or, in the case of ocular-specific criteria, individual eyes with any of the following will not be allowed to participate in this study:
- •Have any uncontrolled systemic disease that, in the opinion of the Investigator, would preclude participation in the study (e.g., infection, uncontrolled elevated blood pressure, cardiovascular disease, or glycemic control issues) or put the participant at risk due to study procedures.
- •Have mutations in genes that cause autosomal dominant retinitis pigmentosa (adRP), X-linked retinitis pigmentosa (XLRP), or presence of biallelic mutations in autosomal recessive RP/retinal dystrophy genes other than PRPF31 mutations.
- •Have used anti-vascular endothelial growth factor (VEGF) agents or corticosteroid injections or implants.
- •Have had Ozurdex® implants placed within 3 months or Retisert® or Iluvien® implants placed within 3 years prior to Visit
- •Within 3 months prior to Visit 2, have undergone any vitreoretinal surgery (scleral buckle, pars plana vitrectomy, retrieval of a dropped nucleus or intraocular lens, radial optic neurotomy, sheathotomy, cyclodestructive procedures or multiple filtration surgeries [2 or more], etc.) or any other ocular surgery.
- •Have ocular media opacity or poor pupillary dilation that prohibits quality ophthalmic evaluation or photography.
- •Have used any investigational drug or device within 90 days or 5 estimated half-lives of Visit 2, whichever is longer, or plan to participate in another study of drug or device during the study period.
- •Have received any prior cell or gene therapy for a retinal condition.
- •Have a history of illicit drug use or alcohol dependency.
研究组 & 干预措施
Vision Cohort 1
Score of ≥ 54 ETDRS letters read and a VF diameter ≥ 10 degrees in every meridian of the central field
Vision Cohort 2
Score of ≥ 35 ETDRS letters read and a VF diameter < 10 degrees in any meridian of the central field
Vision Cohort 3
Score of < 35 ETDRS letters read
结局指标
主要结局
Change from Baseline in Ellipsoid Zone (EZ) Area
时间窗: Baseline through Year 4
Change in EZ area measured using spectral domain optical coherence tomography (SD-OCT), as measured by the central reading center
Change from Baseline in Ellipsoid Zone (EZ) Volume
时间窗: Baseline through Year 4
Change in EZ volume measured using spectral domain optical coherence tomography (SD-OCT), as measured by the central reading center
Ocular Adverse Events (AEs)
时间窗: Screening through Year 4
Frequency of ocular adverse events (AEs)
Change from Baseline in Retinal Thickness
时间窗: Baseline through Year 4
Retinal thickness is measured using spectral domain optical coherence tomography (SD-OCT), as measured by the central reading center
Change from Baseline in Fixation Stability
时间窗: Baseline through Year 4
Fixation stability as measured by Macular Integrity Assessment (MAIA) microperimeter
Change from Baseline in Full Field Retinal Sensitivity
时间窗: Baseline through Year 4
Dark-adapted visual sensitivity via full-field stimulus threshold (FST) measurement
Change from Baseline in Electrical response
时间窗: Baseline through Year 4
Electrical response measured using Full-field electroretinogram (ERG) with specific stimuli
Change in Best Corrected Low Luminance Visual Acuity (LLVA)
时间窗: Baseline through Year 4
Best corrected LLVA letter score measured using the ETDRS charts and a special light filter lens
Change in Patient Reported Outcome Measures using Michigan Retinal Degeneration Questionnaire (MRDQ)
时间窗: Baseline through Year 4
Responses on the MRDQ, a validated patient reported outcomes measure designed in accordance with U.S. FDA guidelines, specifically for conditions of inherited retinal degeneration (IRDs)
Change from Baseline in Best Corrected Visual Acuity (BCVA)
时间窗: Baseline through Year 4
BCVA letter score utilizing ETDRS (Early Treatment Diabetic Retinopathy Study) or BRVT (Berkeley Rudimentary Vision Test) for patients not able to see letters
Characterization of Changes of the Retina with Fundus Photography
时间窗: Baseline through Year 4
Abnormalities captured by fundus photography
Change from Baseline in Area of Fundus Autofluorescence (FAF)
时间窗: Baseline through Year 4
Area of hypo-autofluorescence captured by fundus autofluorescence (FAF)
Change in Patient Reported Outcome Measures using Patient Global Impression of Change (PGI-C) scale
时间窗: Baseline through Year 4
Responses on the PGI-C to assess change of the patient's condition
Change from Baseline in Visual Field Sensitivity
时间窗: Baseline through Year 4
Visual field sensitivity measured by static perimetry with topographic analysis-Hill of Vision conducted by the central reading center
Change from Baseline in Mean Macular Sensitivity
时间窗: Baseline through Year 4
Mean macular sensitivity measured on guided microperimetry
Change from Baseline in Functional Vision
时间窗: 3 times prior to Month 4
Functional vision is measured with a functional mobility course (Ora-VNC™) score
Change in Patient Reported Outcome Measures using Patient Global Impression of Severity (PGI-S) scale
时间窗: Baseline through Year 4
Responses on the PGI-S to assess severity of the patient's condition
Genomic Analysis for Study Eligibility
时间窗: Screening
Whole exome genomic analysis
次要结局
未报告次要终点