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

• ClinicalTrials.gov Identifier: NCT03374657
• Recruitment Status: Active, not recruiting
• First Posted: December 15, 2017
• Last Update Posted: February 8, 2023
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Retinitis Pigmentosa	Biological: CPK850	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Intervention 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 (Outcomes Assessor)

Masking Description

This is a partially masked study. The patients will not be masked. The treating physicians and personnel at the surgical location (surgeons, anesthesiologist, operating room personnel and others) will not be masked.

At the clinical sites, there will be an unmasked ophthalmologist. The remaining assessors at the clinical sites (ophthalmologist, study nurse, ophthalmic technician, etc) doing the ophthalmic examinations should be masked to the study (treated) eye.

The following unmasked sponsor roles are required for this study:

Sponsor clinical staff required to assist in the management and re-supply of investigational drug product.

The independent committee assessing unmasked interim results and the independent analysis team.

All other sponsor staff will stay masked to treatment assignments

• Primary Purpose: Treatment
• 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
• Actual Study Start Date: August 22, 2018
• Estimated Primary Completion Date: May 11, 2026
• Estimated Study Completion Date: May 11, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: CPK Dose 1 (lowest dose); CPK850, one subretinal injection to the study eye	Biological: CPK850; In one of 5 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 5 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 5 dose levels administered via subretinal injection under anesthesia
Experimental: CPK Dose 4 (next to highest dose); CPK850, one subretinal injection to the study eye	Biological: CPK850; In one of 5 dose levels administered via subretinal injection under anesthesia
Experimental: CPK Dose 5 (highest dose); CPK850, one subretinal injection to the study eye	Biological: CPK850; In one of 5 dose levels administered via subretinal injection under anesthesia

Outcome Measures

Primary Outcome Measures :

1. Number of participants with adverse events (AEs), serious adverse events (SAEs) and deaths [ Time Frame: Up to year 5 ]
   Safety events
2. 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 Outcome Measures :

1. Number of patients with recovery of the cone system [ Time Frame: Screening/baseline up to year 1 ]
   cone recovery during dark adaptation
2. 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
3. Change from screening/baseline in Visual field perimetry mean deviation [ Time Frame: Screening/baseline up to year 1 ]
   Assessed using automated static perimetry
4. 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
5. Change from screening/baseline in Light-adapted microperimetry sensitivity [ Time Frame: Screening/baseline up to year 1 ]
   Assessed using standard microperimetry equipment
6. 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
7. 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.
8. Change from screening/baseline in Reading speed [ Time Frame: Screening/baseline up to year 1 ]
   Assessed using standard reading speed charts
9. Change from screening/baseline in eye dominance [ Time Frame: Screening/baseline up to year 1 ]
   Dominant eye for viewing targets at distance
10. 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
11. 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
12. 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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Sweden

Novartis Investigative Site

Stockholm, Sweden, SE-112 82

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03374657
• Other Study ID Numbers: CCPK850X2202; 2016-002696-10 ( EudraCT Number )
• First Posted: December 15, 2017
• Last Update Posted: February 8, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

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.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Clinical trials, dark adaptation, gene therapy, RLBP1 mutation, retinitis pigmentosa.

Additional relevant MeSH terms:

Retinitis; Retinitis Pigmentosa; Retinal Diseases; Eye Diseases; Eye Diseases, Hereditary; Retinal Dystrophies; Retinal Degeneration; Genetic Diseases, Inborn