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

Primary Purpose

Retinitis Pigmentosa

Status

Active

Phase

Phase 1

Locations

Sweden

Study Type

Interventional

Intervention

CPK850

About this trial

This is an interventional treatment trial for Retinitis Pigmentosa focused on measuring Clinical trials, dark adaptation, gene therapy, RLBP1 mutation, retinitis pigmentosa.

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

CPK Dose 1 (lowest dose)

CPK Dose 2 (next lowest dose)

CPK Dose 3 (third lowest dose)

CPK Dose 4 (next to highest dose)

CPK Dose 5 (highest dose)

Arm Description

CPK850, one subretinal injection to the study eye

Outcomes

Primary Outcome Measures

Number of participants with adverse events (AEs), serious adverse events (SAEs) and deaths

Safety events

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.

Secondary Outcome Measures

Number of patients with recovery of the cone system

cone recovery during dark adaptation

Number of patients with improvement in rod function in the treated eye vs the untreated eye

rod function during dark adaptation

Change from screening/baseline in Visual field perimetry mean deviation

Assessed using automated static perimetry

Change from screening/baseline in Total contrast sensitivity score

Contrast sensitivity (ie, the ability to detect relatively dim objects) will be assessed

Change from screening/baseline in Light-adapted microperimetry sensitivity

Assessed using standard microperimetry equipment

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

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.

Change from screening/baseline in Reading speed

Assessed using standard reading speed charts

Change from screening/baseline in eye dominance

Dominant eye for viewing targets at distance

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

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

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

Full Information

NCT ID

NCT03374657

First Posted

December 11, 2017

Last Updated

July 12, 2023

Sponsor

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03374657

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

August 22, 2018 (Actual)

Primary Completion Date

May 11, 2026 (Anticipated)

Study Completion Date

May 11, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Retinitis Pigmentosa

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

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

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

Allocation

Non-Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CPK Dose 1 (lowest dose)

Arm Type

Experimental

Arm Description

CPK850, one subretinal injection to the study eye

Arm Title

CPK Dose 2 (next lowest dose)

Arm Type

Experimental

Arm Description

CPK850, one subretinal injection to the study eye

Arm Title

CPK Dose 3 (third lowest dose)

Arm Type

Experimental

Arm Description

CPK850, one subretinal injection to the study eye

Arm Title

CPK Dose 4 (next to highest dose)

Arm Type

Experimental

Arm Description

CPK850, one subretinal injection to the study eye

Arm Title

CPK Dose 5 (highest dose)

Arm Type

Experimental

Arm Description

CPK850, one subretinal injection to the study eye

Intervention Type

Biological

Intervention Name(s)

CPK850

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of participants with adverse events (AEs), serious adverse events (SAEs) and deaths

Description

Safety events

Time Frame

Up to year 5

Title

Number of responders in dark adaptation

Description

Time Frame

Screening/baseline up to year 1

Secondary Outcome Measure Information:

Title

Number of patients with recovery of the cone system

Description

cone recovery during dark adaptation

Time Frame

Screening/baseline up to year 1

Title

Number of patients with improvement in rod function in the treated eye vs the untreated eye

Description

rod function during dark adaptation

Time Frame

Screening/baseline up to year 1

Title

Change from screening/baseline in Visual field perimetry mean deviation

Description

Assessed using automated static perimetry

Time Frame

Screening/baseline up to year 1

Title

Change from screening/baseline in Total contrast sensitivity score

Description

Contrast sensitivity (ie, the ability to detect relatively dim objects) will be assessed

Time Frame

Screening/baseline up to year 1

Title

Change from screening/baseline in Light-adapted microperimetry sensitivity

Description

Assessed using standard microperimetry equipment

Time Frame

Screening/baseline up to year 1

Title

Change from screening/baseline in the local electrical activity of the retina

Description

Assessed using a system designed to record multifocal electroretinogram (ERG) responses from a number of locations at one time

Time Frame

Screening/baseline up to year 1

Title

Change from screening/baseline in the electrical activity of the retina

Description

Assessed using a system designed to record full-field electroretinogram (ERG) responses with Ganzfeld stimulation.

Time Frame

Screening/baseline up to year 1

Title

Change from screening/baseline in Reading speed

Description

Assessed using standard reading speed charts

Time Frame

Screening/baseline up to year 1

Title

Change from screening/baseline in eye dominance

Description

Dominant eye for viewing targets at distance

Time Frame

Screening/baseline up to year 1

Title

Change from screening/baseline in Change from baseline in mobility test scores

Description

Assessed using a system designed to measure the ability to navigate obstacles in a maze-like environment under varying light conditions

Time Frame

Screening/baseline up to year 1

Title

Change from screening/baseline in the National Eye Institute - Visual function questionnaire 25 (NEI-VFQ 25) composite score

Description

Questionnaire completed by the participant to measure the influence of visual impairment on quality of life

Time Frame

Screening/baseline up to year 1

Title

Change from screening/baseline in the low luminance questionnaire (LLQ) responses

Description

Questionnaire completed by the participant to assess visual problems under low luminance conditions, including nighttime

Time Frame

Screening/baseline up to year 1

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Novartis Pharmaceuticals

Organizational Affiliation

Novartis Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Novartis Investigative Site

City

Stockholm

ZIP/Postal Code

SE-112 82

Country

Sweden

12. IPD Sharing Statement

Plan to Share IPD

Undecided

IPD Sharing 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.

Learn more about this trial

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

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