A First-in-human, Proof of Concept Study of CPK850 in Patients With RLBP1 Retinitis Pigmentosa

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Retinitis Pigmentosa

Intervention / Treatment
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* Biological: CPK850


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: This is a non-confirmatory, open-label single ascending dose gene replacement-therapy study to assess safety, tolerability and efficacy of CPK850 in patients with RLBP1 retinitis pigmentosa due to biallelic mutations in the RLBP1 gene. The trial design uses a staggered patient enrollment.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPK Dose 1 (lowest dose)<br>CPK850, one subretinal injection to the study eye | Biological: CPK850<br>* In one of 4 dose levels administered via subretinal injection under anesthesia<br>|
| Experimental: CPK Dose 2 (next lowest dose)<br>CPK850, one subretinal injection to the study eye | Biological: CPK850<br>* In one of 4 dose levels administered via subretinal injection under anesthesia<br>|
| Experimental: CPK Dose 3 (third lowest dose)<br>CPK850, one subretinal injection to the study eye | Biological: CPK850<br>* In one of 4 dose levels administered via subretinal injection under anesthesia<br>|
| Experimental: CPK Dose 4 (highest dose)<br>CPK850, one subretinal injection to the study eye | Biological: CPK850<br>* In one of 4 dose levels administered via subretinal injection under anesthesia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs), serious adverse events (SAEs) and deaths | Safety events | Up to year 5 | 
| Number of responders in dark adaptation | 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. | Screening/baseline up to year 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with recovery of the cone system | cone recovery during dark adaptation | Screening/baseline up to year 1 | 
| Number of patients with improvement in rod function in the treated eye vs the untreated eye | rod function during dark adaptation | Screening/baseline up to year 1 | 
| Change from screening/baseline in Visual field perimetry mean deviation | Assessed using automated static perimetry | Screening/baseline up to year 1 | 
| Change from screening/baseline in Total contrast sensitivity score | Contrast sensitivity (ie, the ability to detect relatively dim objects) will be assessed | Screening/baseline up to year 1 | 
| Change from screening/baseline in Light-adapted microperimetry sensitivity | Assessed using standard microperimetry equipment | Screening/baseline up to year 1 | 
| Change from screening/baseline in the local electrical activity of the retina | Assessed using a system designed to record multifocal electroretinogram (ERG) responses from a number of locations at one time | Screening/baseline up to year 1 | 
| Change from screening/baseline in the electrical activity of the retina | Assessed using a system designed to record full-field electroretinogram (ERG) responses with Ganzfeld stimulation. | Screening/baseline up to year 1 | 
| Change from screening/baseline in Reading speed | Assessed using standard reading speed charts | Screening/baseline up to year 1 | 
| Change from screening/baseline in eye dominance | Dominant eye for viewing targets at distance | Screening/baseline up to year 1 | 
| Change from screening/baseline in Change from baseline in mobility test scores | Assessed using a system designed to measure the ability to navigate obstacles in a maze-like environment under varying light conditions | Screening/baseline up to year 1 | 
| Change from screening/baseline in the National Eye Institute - Visual function questionnaire 25 (NEI-VFQ 25) composite score | Questionnaire completed by the participant to measure the influence of visual impairment on quality of life | Screening/baseline up to year 1 | 
| Change from screening/baseline in the low luminance questionnaire (LLQ) responses | Questionnaire completed by the participant to assess visual problems under low luminance conditions, including nighttime | Screening/baseline up to year 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Clinical trials, dark adaptation, gene therapy, RLBP1 mutation, retinitis pigmentosa.