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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: July 28, 2026

Detailed Description

This study will potentially include 5 cohorts with a minimum of 3 patients per cohort, with an optional cohort of up to 6 patients. This trial design uses 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.

Interventions

  • Biological: CPK850
    • In one of 5 dose levels administered via subretinal injection under anesthesia

Arms, Groups and Cohorts

  • Experimental: CPK Dose 1 (lowest dose)
    • CPK850, one subretinal injection to the study eye
  • Experimental: CPK Dose 2 (next lowest dose)
    • CPK850, one subretinal injection to the study eye
  • Experimental: CPK Dose 3 (third lowest dose)
    • CPK850, one subretinal injection to the study eye
  • Experimental: CPK Dose 4 (next to highest dose)
    • CPK850, one subretinal injection to the study eye
  • Experimental: CPK Dose 5 (highest dose)
    • CPK850, one subretinal injection to the study eye

Clinical Trial Outcome Measures

Primary Measures

  • Number of participants with adverse events (AEs), serious adverse events (SAEs) and deaths
    • Time Frame: Up to year 5
    • Safety events
  • Number of responders in dark adaptation
    • Time Frame: 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.

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Novartis Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Novartis Pharmaceuticals, Study Director, Novartis Pharmaceuticals
  • Overall Contact(s)
    • Novartis Pharmaceuticals, +41613241111, novartis.email@novartis.com

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