Clinical trial NCT03374657: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Retinitis Pigmentosa
Keywords: Clinical trials, dark adaptation, gene therapy, RLBP1 mutation, retinitis pigmentosa.
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-12-15
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
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

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.

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

Primary outcomes:
measure: Number of participants with adverse events (AEs), serious adverse events (SAEs) and deaths
timeFrame: Up to year 5
measure: Number of responders in dark adaptation
timeFrame: Screening/baseline up to year 1
Secondary outcomes:
measure: Number of patients with recovery of the cone system
timeFrame: Screening/baseline up to year 1
measure: Number of patients with improvement in rod function in the treated eye vs the untreated eye
timeFrame: Screening/baseline up to year 1
measure: Change from screening/baseline in Visual field perimetry mean deviation
timeFrame: Screening/baseline up to year 1
measure: Change from screening/baseline in Total contrast sensitivity score
timeFrame: Screening/baseline up to year 1
measure: Change from screening/baseline in Light-adapted microperimetry sensitivity
timeFrame: Screening/baseline up to year 1
measure: Change from screening/baseline in the local electrical activity of the retina
timeFrame: Screening/baseline up to year 1
measure: Change from screening/baseline in the electrical activity of the retina
timeFrame: Screening/baseline up to year 1
measure: Change from screening/baseline in Reading speed
timeFrame: Screening/baseline up to year 1
measure: Change from screening/baseline in eye dominance
timeFrame: Screening/baseline up to year 1
measure: Change from screening/baseline in Change from baseline in mobility test scores
timeFrame: Screening/baseline up to year 1
measure: Change from screening/baseline in the National Eye Institute - Visual function questionnaire 25 (NEI-VFQ 25) composite score
timeFrame: Screening/baseline up to year 1
measure: Change from screening/baseline in the low luminance questionnaire (LLQ) responses
timeFrame: Screening/baseline up to year 1
Other outcomes:
Locations:
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: