Retinitis Pigmentosa
Conditions
Keywords
Clinical trials, dark adaptation, gene therapy, RLBP1 mutation, retinitis pigmentosa.
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.
Interventions
BIOLOGICALCPK850
In one of 4 dose levels administered via subretinal injection under anesthesia
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
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
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Number of responders with recovery of the cone system | Screening/baseline up to Year 1 | cone recovery during dark adaptation |
| Change from screening/baseline in Visual field perimetry mean deviation | Screening/baseline up to Year 2 | Assessed using automated static perimetry |
| Change from screening/baseline in Total contrast sensitivity score | Screening/baseline up to Year 2 | Contrast sensitivity (ie, the ability to detect relatively dim objects) will be assessed |
| Change from screening/baseline in Light-adapted microperimetry sensitivity | Screening/baseline up to Year 5 | Assessed using standard microperimetry equipment |
| Change from screening/baseline in the local electrical activity of the retina | Screening/baseline up to Year 2 | 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 | Screening/baseline up to Year 5 | Assessed using a system designed to record full-field electroretinogram (ERG) responses with Ganzfeld stimulation. |
| Change from screening/baseline in Reading speed | Screening/baseline up to Year 2 | Assessed using standard reading speed charts |
| Change from screening/baseline in eye dominance | Screening/baseline up to Year 5 | Dominant eye for viewing targets at distance |
| Change from screening/baseline in Change from baseline in mobility test scores | Screening/baseline up to Year 2 | 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 | Screening/baseline up to Year 5 | 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 | Screening/baseline up to Year 5 | Questionnaire completed by the participant to assess visual problems under low luminance conditions, including nighttime |
Countries
Sweden
Contacts
STUDY_DIRECTORNovartis Pharmaceuticals
Novartis Pharmaceuticals
Outcome results
None listed