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

Phase 1

Active, not recruiting

• Conditions: Retinitis Pigmentosa
• Interventions: Biological: CPK850

• Registration Number: NCT03374657
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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

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 Timeline

• Study First Submitted: 2017-12-11
• Study First Submitted QC: 2017-12-11
• Study First Posted: 2017-12-15
• Study Start: 2018-08-22
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-09
• Last Update Posted: 2025-01-10
• Primary Completion: 2026-05-11
• Study Completion: 2026-05-11

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 12

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CPK Dose 3 (third lowest dose)	CPK850	CPK850, one subretinal injection to the study eye
CPK Dose 4 (highest dose)	CPK850	CPK850, one subretinal injection to the study eye
CPK Dose 1 (lowest dose)	CPK850	CPK850, one subretinal injection to the study eye
CPK Dose 2 (next lowest dose)	CPK850	CPK850, one subretinal injection to the study eye

Primary Outcome Measures

Name	Time	Method
Number of participants with adverse events (AEs), serious adverse events (SAEs) and deaths	Up to year 5	Safety events
Number of responders in dark adaptation	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 Outcome Measures

Name	Time	Method
Change from screening/baseline in Change from baseline in mobility test scores	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 local electrical activity of the retina	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
Number of patients with recovery of the cone system	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	Screening/baseline up to year 1	rod function during dark adaptation
Change from screening/baseline in Total contrast sensitivity score	Screening/baseline up to year 1	Contrast sensitivity (ie, the ability to detect relatively dim objects) will be assessed
Change from screening/baseline in Visual field perimetry mean deviation	Screening/baseline up to year 1	Assessed using automated static perimetry
Change from screening/baseline in eye dominance	Screening/baseline up to year 1	Dominant eye for viewing targets at distance
Change from screening/baseline in Light-adapted microperimetry sensitivity	Screening/baseline up to year 1	Assessed using standard microperimetry equipment
Change from screening/baseline in Reading speed	Screening/baseline up to year 1	Assessed using standard reading speed charts
Change from screening/baseline in the electrical activity of the retina	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 the low luminance questionnaire (LLQ) responses	Screening/baseline up to year 1	Questionnaire completed by the participant to assess visual problems under low luminance conditions, including nighttime
Change from screening/baseline in the National Eye Institute - Visual function questionnaire 25 (NEI-VFQ 25) composite score	Screening/baseline up to year 1	Questionnaire completed by the participant to measure the influence of visual impairment on quality of life

Trial Locations

Locations (1)

Novartis Investigative Site; 🇸🇪 Stockholm, Sweden