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

Sponsors

Lead Sponsor: Novartis Pharmaceuticals

Source Novartis
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 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.

Overall Status Recruiting
Start Date August 22, 2018
Completion Date July 29, 2026
Primary Completion Date July 28, 2026
Phase Phase 1/Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of participants with adverse events (AEs), serious adverse events (SAEs) and deaths Up to year 5
Number of responders in dark adaptation Screening/baseline up to year 1
Secondary Outcome
Measure Time Frame
Number of patients with recovery of the cone system Screening/baseline up to year 1
Number of patients with improvement in rod function in the treated eye vs the untreated eye Screening/baseline up to year 1
Change from screening/baseline in Visual field perimetry mean deviation Screening/baseline up to year 1
Change from screening/baseline in Total contrast sensitivity score Screening/baseline up to year 1
Change from screening/baseline in Light-adapted microperimetry sensitivity Screening/baseline up to year 1
Change from screening/baseline in the local electrical activity of the retina Screening/baseline up to year 1
Change from screening/baseline in the electrical activity of the retina Screening/baseline up to year 1
Change from screening/baseline in Reading speed Screening/baseline up to year 1
Change from screening/baseline in eye dominance Screening/baseline up to year 1
Change from screening/baseline in Change from baseline in mobility test scores Screening/baseline up to year 1
Change from screening/baseline in the National Eye Institute - Visual function questionnaire 25 (NEI-VFQ 25) composite score Screening/baseline up to year 1
Change from screening/baseline in the low luminance questionnaire (LLQ) responses Screening/baseline up to year 1
Enrollment 21
Condition
Intervention

Intervention Type: Biological

Intervention Name: CPK850

Description: In one of 5 dose levels administered via subretinal injection under anesthesia

Eligibility

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

Gender: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Novartis Pharmaceuticals Study Director Novartis Pharmaceuticals
Overall Contact

Last Name: Novartis Pharmaceuticals

Phone: +41613241111

Email: [email protected]

Location
Facility: Status: Novartis Investigative Site
Location Countries

Sweden

Verification Date

May 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 5
Arm Group

Label: CPK Dose 1 (lowest dose)

Type: Experimental

Description: CPK850, one subretinal injection to the study eye

Label: CPK Dose 2 (next lowest dose)

Type: Experimental

Description: CPK850, one subretinal injection to the study eye

Label: CPK Dose 3 (third lowest dose)

Type: Experimental

Description: CPK850, one subretinal injection to the study eye

Label: CPK Dose 4 (next to highest dose)

Type: Experimental

Description: CPK850, one subretinal injection to the study eye

Label: CPK Dose 5 (highest dose)

Type: Experimental

Description: CPK850, one subretinal injection to the study eye

Patient Data Undecided
Study Design Info

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.

Primary Purpose: Treatment

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

Source: ClinicalTrials.gov