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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Retinitis Pigmentosa
• Intervention / Treatment: Biological: CPK850

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, SE-112 82
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Kvanta A, Rangaswamy N, Holopigian K, Watters C, Jennings N, Liew MSH, Bigelow C, Grosskreutz C, Burstedt M, Venkataraman A, Westman S, Geirsdottir A, Stasi K, Andre H. Interim safety and efficacy of gene therapy for RLBP1-associated retinal dystrophy: a phase 1/2 trial. Nat Commun. 2024 Sep 10;15(1):7438. doi: 10.1038/s41467-024-51575-4.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2018
• Primary Completion (Estimated): May 11, 2026
• Study Completion (Estimated): May 11, 2026

Study Registration Dates

• First Submitted: December 11, 2017
• First Submitted That Met QC Criteria: December 11, 2017
• First Posted (Actual): December 15, 2017

Study Record Updates

• Last Update Posted (Actual): January 15, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Clinical trials, dark adaptation, gene therapy, RLBP1 mutation, retinitis pigmentosa.
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Eye Diseases; Eye Diseases, Hereditary; Retinal Diseases; Retinal Dystrophies; Retinal Degeneration; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Retinitis Pigmentosa
• Other Study ID Numbers: CCPK850X2202; 2016-002696-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No