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

Retinitis Pigmentosa Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03374657
• Other study ID #: CCPK850X2202
• Secondary ID: 2016-002696-10
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: August 22, 2018
• Est. completion date: May 11, 2026

Study information

• Verified date: December 2023
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 12
• Est. completion date: May 11, 2026
• Est. primary completion date: May 11, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Retinitis
• Retinitis Pigmentosa

Intervention

Biological:
• CPK850
In one of 4 dose levels administered via subretinal injection under anesthesia

Locations

Country	Name	City	State
Sweden	Novartis Investigative Site	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events (AEs), serious adverse events (SAEs) and deaths	Safety events	Up to year 5
Primary	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	Number of patients with recovery of the cone system	cone recovery during dark adaptation	Screening/baseline up to year 1
Secondary	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
Secondary	Change from screening/baseline in Visual field perimetry mean deviation	Assessed using automated static perimetry	Screening/baseline up to year 1
Secondary	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
Secondary	Change from screening/baseline in Light-adapted microperimetry sensitivity	Assessed using standard microperimetry equipment	Screening/baseline up to year 1
Secondary	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
Secondary	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
Secondary	Change from screening/baseline in Reading speed	Assessed using standard reading speed charts	Screening/baseline up to year 1
Secondary	Change from screening/baseline in eye dominance	Dominant eye for viewing targets at distance	Screening/baseline up to year 1
Secondary	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
Secondary	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
Secondary	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