An Open-label First-in-human Single Ascending Dose Study to Explore Safety, Tolerability and Efficacy of Subretinal Administration of CPK850 Gene Therapy in Patients With Retinitis Pigmentosa Due to Mutations in the Retinaldehyde Binding Protein 1 (RLBP1) Gene
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Number of participants with adverse events (AEs), serious adverse events (SAEs) and deaths
研究概览
简要总结
The purpose of this first-in-human study is to explore the maximum tolerated dose (MTD) of CPK850 as determined by the single ascending dose ranging portion of the study. This study will also evaluate the safety and potential efficacy of CPK850 on improving visual function in patients with decreased visual function from RLBP1 retinitis pigmentosa due to biallelic mutations in the RLBP1 gene.
详细描述
This study will potentially include 4 cohorts with a minimum of 3 patients per cohort. This trial design used a staggered patient enrollment with continuous data reviews to limit as much unforeseen risk as possible prior to enrolling each patient in each cohort or initiating another cohort. Only one eye (designated as the study or treated eye) will be dosed per patient. Each patient will be followed for 5 years after the subretinal injection of CPK850.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
This is a partially masked study. The patients will not be masked. The treating physicians and personnel at the surgical location (surgeons, anesthesiologist, operating room personnel and others) will not be masked.
At the clinical sites, there will be an unmasked ophthalmologist. The remaining assessors at the clinical sites (ophthalmologist, study nurse, ophthalmic technician, etc) doing the ophthalmic examinations should be masked to the study (treated) eye.
The following unmasked sponsor roles are required for this study:
Sponsor clinical staff required to assist in the management and re-supply of investigational drug product.
The independent committee assessing unmasked interim results and the independent analysis team.
All other sponsor staff will stay masked to treatment assignments
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients aged 18 to 70 years inclusive.
- •The visual acuity in the study eye at the screening 1 visit should be no better than 60 ETDRS letters.
- •Clinical diagnosis of Bothnia dystrophy, Newfoundland rod-cone dystrophy or other progressive retinitis pigmentosa phenotype with mutations in the RLBP1 gene verified by genetic testing.
- •Visible photoreceptor (outer nuclear) and Retinal Pigment Epithelium (RPE) layers on standard OCT scan in the study eye at the screening 1 visit.
排除标准
- •History of hypersensitivity to the study drug or to drugs of similar classes or to any of the medications required in the perioperative period.
- •Pre-existing eye conditions that would preclude the planned surgery or interfere with the interpretation of study endpoints
- •Any contraindication to the planned surgery or anesthesia as determined by the treating physician (surgeon, anesthesiologist, internist, or designee).
- •Women who are pregnant, or lactating or women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for two months after treatment
研究组 & 干预措施
CPK Dose 3 (third lowest dose)
CPK850, one subretinal injection to the study eye
干预措施: CPK850 (Biological)
CPK Dose 4 (highest dose)
CPK850, one subretinal injection to the study eye
干预措施: CPK850 (Biological)
CPK Dose 1 (lowest dose)
CPK850, one subretinal injection to the study eye
干预措施: CPK850 (Biological)
CPK Dose 2 (next lowest dose)
CPK850, one subretinal injection to the study eye
干预措施: CPK850 (Biological)
结局指标
主要结局
Number of participants with adverse events (AEs), serious adverse events (SAEs) and deaths
时间窗: Up to year 5
Safety events
Number of responders in dark adaptation
时间窗: Screening/baseline up to year 1
A patient is considered a responder if sensitivity recovery values at 1 hour post-bleach are observed to be outside of the patient's prediction interval at ≥2 consecutive post-treatment visits within one year after treatment.
Number of participants with adverse events (AEs), serious adverse events (SAEs) and deaths
时间窗: Up to Year 5
Safety events
Number of responders in dark adaptation
时间窗: Screening/baseline up to Year 1
A patient is considered a responder if sensitivity recovery values at 1 hour post-bleach are observed to be outside of the patient's prediction interval at ≥2 consecutive post-treatment visits within one year after treatment.
次要结局
- Change from screening/baseline in the local electrical activity of the retina(Screening/baseline up to year 1)
- Change from screening/baseline in Change from baseline in mobility test scores(Screening/baseline up to year 1)
- Number of patients with recovery of the cone system(Screening/baseline up to year 1)
- Number of patients with improvement in rod function in the treated eye vs the untreated eye(Screening/baseline up to year 1)
- Change from screening/baseline in Visual field perimetry mean deviation(Screening/baseline up to year 1)
- Change from screening/baseline in eye dominance(Screening/baseline up to year 1)
- Change from screening/baseline in Reading speed(Screening/baseline up to year 1)
- Change from screening/baseline in Total contrast sensitivity score(Screening/baseline up to year 1)
- Change from screening/baseline in Light-adapted microperimetry sensitivity(Screening/baseline up to year 1)
- Change from screening/baseline in the electrical activity of the retina(Screening/baseline up to year 1)
- Change from screening/baseline in the low luminance questionnaire (LLQ) responses(Screening/baseline up to year 1)
- Change from screening/baseline in the National Eye Institute - Visual function questionnaire 25 (NEI-VFQ 25) composite score(Screening/baseline up to year 1)
- Number of responders with recovery of the cone system(Screening/baseline up to Year 1)
- Change from screening/baseline in Visual field perimetry mean deviation(Screening/baseline up to Year 2)
- Change from screening/baseline in Total contrast sensitivity score(Screening/baseline up to Year 2)
- Change from screening/baseline in Light-adapted microperimetry sensitivity(Screening/baseline up to Year 5)
- Change from screening/baseline in the local electrical activity of the retina(Screening/baseline up to Year 2)
- Change from screening/baseline in the electrical activity of the retina(Screening/baseline up to Year 5)
- Change from screening/baseline in Reading speed(Screening/baseline up to Year 2)
- Change from screening/baseline in eye dominance(Screening/baseline up to Year 5)
- Change from screening/baseline in Change from baseline in mobility test scores(Screening/baseline up to Year 2)
- Change from screening/baseline in the National Eye Institute - Visual function questionnaire 25 (NEI-VFQ 25) composite score(Screening/baseline up to Year 5)
- Change from screening/baseline in the low luminance questionnaire (LLQ) responses(Screening/baseline up to Year 5)